Gpat 2018 PDF

TEST PAPER-10 PHARMACEUTICAL CHEMISTRY GPAT TEST SERIES BY PHARMAROCKS
PHARMAROCKS
THE WAY OF SUCCESS
GPAT STUDY MATERIAL

MR. AMAR M. RAVAL
PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 12

PHARMAROCKS GPAT SUCCESS SERIES-2016: THE WAY OF SUCCESS IMP STUDY MATERIAL
DRUGS AND THEIR ACTIVE METABOLITES
SR.NO. DRUG ACTIVE METABOLITE

1 Allopurinol Oxipurinol (Alloxanthine)
2 Amytryptylline Nortryptalline
3 Amphetamine P-Methoxy Amphetamine
4 Carmapazepine Carmapazemine-10,11-Eporide
5 Carbimazole Thiamazole
6 Cephaloglycine Desacetyl Cephaloglycine
7 Chloral Hydrate Trichloroethanol
8 Chlordiazepoxide 7-hydroxy Chloropromazine
9 Chlorpromazine 7-hydroxy Chloropromazine
10 Chlorguanidine Cyclogunal
11 Clofibrate Free acid metabolite
12 Imipramine N-oxide metabolite
13 Codeine Morphine,Norcodeine
14 Diazepam Oxazepam.N-Me-Oxazepam
15 Fenfluramine Nor Fenfluramine
16 Guanethadine N-Oxide
17 Lignocaine N-Desmethyl metabolite
18 Morphine Nor morphine
19 Naloxane 6- -hydroxy Naloxane
20 Phenacetin Paracetamol
21 Prednisone Prednisolone
22 Premidone Phenobarbitone
23 Spironolactone Canrenone
24 Procainamide N-Acetyl metabolite
25 Propanolol N-deisopropyl met
26 Quinidine 3-Hydroxy quinone
27 Rifampicine Desacetylated metabolite
28 Thioridazine Mesoridazine

29 Trimethedione Dimethedione
30 Warfarin Warfarin alcohol
31 Vit D 1,2 Dihydroxy metabolite
32 Reserpine Methyl reserpate
PRODUCTS AND ANIMALS USED FOR BIOASSAYS
SR DRUG PRODUCT ANIMAL
1 Digitalis Pigeon
2 Glycogen Cat
3 Insulin inj, Rabbit
4 Oxytocin Chicken
5 Parathyroid Dog
6 Vasopressin Rat
7 Posterior pituitary Chicken
8 Tubocurarine chloride Rabbit
9 Chorionic gonadotropin Male rat
10 Cod liver oil Rachitic rat
11 Heparin sodium Sheep
12 Iron dextran injection Microbial cultures
13 Antiseptic and disinfectant Frog
14 Fungicides and Herbicides Mouse
15 Diphtheria toxoid Rat
16 Atropine Rabbit
17 Insulin inj. Guinea pig
18 Elastomeric closures Plastic containers Guinea pig

RECOMENDE NEEDLE SIZE FOR VARIOUS INJECTIONS
INJECTIONS GUAGE LENGTH IN INCHES
INTRADERMAL 26G ¼ or 3/8
S.C 26G ½-¾
25G ½-¾
22G 1½
I.M 24G ¾-1
23G 1
22G 1
20G 1½
I.V 22G 1-1/4-1 ½
20G 1½
DRUGS AND THEIR VARIETIES
DRUG VARIETY
1 SENNA
Indian senna Cassia angustifolia
Alexandrian senna Cassia acutifolia
Dog senna Cassia obovata
Palthe senna Cassia auriculata
2 ALOE
Cape Aloe Aloe ferox
Curcao Aloe Aloe barbadensis
Socotriene/ Zangibar aloe Aloe perryii
3 RHUBARB
Indian Rhubarb Rheum emodi
Chienese Rhubarb Rheum Webbianum

DRUG AND THEIR SYNONYMS
SR.NO. DRUG SYNONYMS
1 Cinchona Panama bark

2 Lanolin Wool fat
3 Crowfig seeds Nuxvomica
4 Deadly night shade Atropa beladona
5 Digitalis purpuria Foxglove
6 American podophyllum May apple
7 Indian tragacanth Gum karaya
8 Devil’s dung Asafoetida
9 Indian squill Urgenia
10 Indian tobacco Lobelia
11 Flax seeds Linseed
12 Periwinkle Vinca visea
13 Ashwagandha Withania somnifera
14 Alexendrian senna Cassia acutifolia
15 Tinevally senna Cassia angustifolia
16 Dog senna Cassia obovata
17 Pathe senna Cassia auriculata
18 Acasia Gum arabica
19 Sterculia Karaya
20 Agar Japnese is linglass
21 Plantago Psyllium
22 Starch Amylum
23 Rhubarb Rheam.emodi.(IND.Rhubarb)
24 Cascara Purshiana,sacred barc
25 Discoria Wild Yam
26 Glycerrhiza Liquarice
27 Quillalia Panama bark
28 Quassia Bitter wool

29 Pale calicher Gambier catechu

30 Blach caticher Cutch
31 Castor oil Ricinus oil
32 Arachis oil Reauut oil
33 Linseed iol Flax seed oil
34 Olive oil Saled oil
35 Hydro carpno oil Chanlmogra oil
36 Theobrona oil Cocoa butter
37 Cinnamon Chinese cassia
38 Saffron Crocus
39 Colchicum Autumn Crocus, Meadow saffron seeds
40 Nutmeg Mygistica
41 Chenopodium American wore
42 Lipstick tree Annato tree, Bixin
43. Clove Caryo phylum
NAME OF THE DRUG AND SIDE EFFECTS
SR NO NAME OF THE DRUG SIDE EFFECTS
1 ACE Inhibitors Dry Cough

2 Amphotericin-B Nephrotoxicity
3 Ampicillin Hypersensitivity
4 Androgen Virilization
5 Antipsychotics Sedation,
Orthostatic hypotension,
Tardive dyskinesia
6 Anti- TB Hepatotoxicity
7 Aspirin (cox-I Inhibitors) Hepatotoxicity
8 Atropine Dryness of mouth,
Blurred vision,
Constipation

9 Celecoxib, Hepatotoxicity
Valdecoxib (cox-II Inhibitors)
10 Chlorambucil Alopecia
11 Chloramphenicol Grey baby syndrome,
Bone marrow depression
12 Chloroquine Phototoxicity
13 Ciprofloxacin Phototoxicity
14 Clofazimine Pigmentation of skin,
Discoloration of Urine
15 Clozapine Agranulocytosis
16 Erythromyicin Cholestatic Juandice
17 Ethambutol Optic Neuritis,
Retrobulbular Neuritis
18 Hydrochlorthiazide Hypokalamia
19 Isoniazid Peripheral Neurtis
20 Metronidazole Disulfiram like reaction
21 Minoxidil Hirsutism
22 Morphine Constipation
23 Nimesulide Hepatotoxicity
24 Nitrogen Mustard Bone marrow depression
25 Nitroglycerin Palpitation
26 Penicillin-G Jarisch Heximer Reaction
27 Phenformin Lactic acidosis,
GI disturbance,
Metalic taste
28 Phenytoin Hirsutism
29 Quinidine Cinchonism
30 Quinine Sulphate Black Water Fever
31 Repaglinide Althralgia
32 Rosaglitazone Anemia,Weight gain
33 Sitagliptin Coldness

34 Spironolactone Hyperkalamia
35 Cimetidine Gynacomastia
37 Sulfonyl Ureas derivatives Bone marrow depression
38 Terfenadine Type-I arrhythmia
39 Tetracyclines Discoloration of teeth
40 Thalidomide Phocomelia
CAPSULE NO & THEIR APPROXIMATE CAPACITY IN mg & ml
CAPSULE SIZE Mg Ml
000 (Largest) 950 1.37
00 650 0.95
0 450 0.68
1 300 0.50
2 250 0.37
3 200 0.30
4 150 0.21
5 (Smallest) 100 0.13
PROPORTIONS REQUIRED FOR A PRIMARY EMULSION
TYPE OF OIL OIL: WATER: GUM RATIO

FIXED OILS 4:2:1
VOLATILE OILS 2:2:1
MINERAL OILS 3:2:1
OLEORESINS 1:2:1
CODE: LPSO (APPLY THIS FOR TWEENS & SPANS)

For eg. SPANS 20 MEAN SORBITAN MONO LAURATE
TWEEN 80 MEAN POLYOXYETHYLENE SORBITAN MONOOLEATE
 L : LAURATE - 20
 P : PALMITATE - 40
 S : STEARATE - 60
 O : OLEATE - 80

SOLUBILITY
Descriptive Term Approx. Vol of Solvent in ml/gm of Solute
Very soluble less than 1
Freely soluble 1 to 10
Soluble 10 to 30
Sparingly soluble 30 to 100
Slightly soluble 100 to 1000
Very slightly soluble 1000 to 10,000
Practically insoluble more than 10,000
STORAGE TEMPERATURE
COLD TEMPERATURE 2 to 8 degree centigrade
COOL TEMPERATURE 8 to 25
ROOM TEMPERATURE Prevailing in the working area
WARM TEMPERATURE Between 30 to 40
EXCESSIVE HEAT > 40 degree
SUCROSE BASED DILUANTS

DIPAC 97 % sucrose + 3% moddified dextrose
NUTAB 95 % sucrose + 4 % invert sugar
SUGAR TAB 90 - 93 % sucrose + 7 - 10 % invert sugar
Carr’s index
The bulk density was the quotient of weight to the volume of the sample. Tapped density was
determined as the quotient of weight of the sample to the volume after tapping a measuring
cylinder for 500 times from a height of 2 inch. The Carr’s index (percentage compressibility)
was calculated as one hundred times the ratio of the difference between tapped density and
bulk density to the tapped density

% Carr’s Index = (Tapped density – Bulk density) / Tapped density * 100

% Carr’s Index = (TD – BD) / TD * 100
Hausner’s Ratio
Hausner’s ratio is the ratio of tapped density to the bulk density.
Hausner’s Ratio = Tapped density / Bulk density H.R = TD / BD
% CI FLOW CHARACTER HAUSNER RATIO

< or = 10 Excellent 1 - 1.11
11 – 15 Good 1.12 - 1.18
16 – 20 Fair 1.19 - 1.25
21 – 25 passable 1.26 - 1.34
26 – 31 poor 1.35 - 1.45
32 – 37 very poor 1.46 - 1.59
>38 very very poor > 1.6
Angle of repose
The angle of repose is a relatively simple technique for estimating the flow properties of a
powder. It can easily be determined by allowing a powder to flow through a funnel and fall
freely onto a surface. The height and diameter of the resulting cone are measured and the
angle of repose calculated from this equation:
Tan Ø = h/r
Where, ‘h’ is the height of the powder cone and ‘r’ is the radius of the powder cone.
ANGLE OF REPOSE FLOW CHARACTER
25 – 30 Excellent
31 – 35 Good
36 – 40 Fair
41 – 45 Passable
46 – 55 Poor
56 – 65 Very Poor
>66 Very Very Poor

TYPES OF GLASS USED IN PHARMACEUTICAL INDUSTRIES
Parenteral Use
 Type I Glass:
 Highly Resistant Borosillicate.
 Used for Buffered and Unbuffered aqueous solution.
 Type II Glass:
 Highly Resistant Sodalime glass.
 Buffered aqueous solution below pH 7.0
 Type III Glass:

 Moderately Resistant Sodalime glass.
 Used for dry powder and oily solution.
 Non-Parenteral Use
 Type IV Glass:
 General Purpose Sodalime glass.
 Not for parenteral, for tablet, liquid oral and externals.
ANTIDOTES FOR SOME DRUGS
SR NO DRUG NAME ANTIDOTE
1 Acetaminophen NAC (N-acetyl-L-cysteine) dosage
Alcohols (ethylene glycol, IV ethanol, fomepizol (potent inhibitor of ADH)

2 methanol)
3 Heparin Protamine
4 Warfarin vitamin k
5 Antidepressants
TCA’s benzodiazepines, phenytoin, physiostigmine
SSRI’s Cycloheptadine
6 6.Benzodiazepines Flumazenil

7 7.Beta antagonists glucagon and epinephrine
8 Calcium antagonists calcium, glucagon, insuline & dextrose combination
Cocaine BZD’s for seizuries; labetalol for hypertension;

9 Neuroleptics for psychosis
10 Cyanide amyl nitrite; sodium nitrite; sodium thio sulphate
11 Digoxin Digibind
12 12.Electrolytes
a.Magnesium 10%CaCl2 temp to antagonize cardiac effects of Mg
b.Potassium- 10%CaCl2 10%; NaHCO3(causes intracellular shift

of pot);
13 Iron deferoxamine (chelate iron)
14 Isoniazid pyridoxine (reverses INH induced seizures)
15 Lead Ca Disodium EDTA ; BAL (dimercaprol)
16 Lithium no effective treatment
17 Opiates naloxone; nalmefene
18 Organophosphates atropine; pralidoxamine
19 Salicylates activated charcoal
20 Theophylline charcoal; beta antagonists
glucose & Insulin sodium polystyrene sulfonate

21 (Intracellular shift of pot.) (cationic exchange resin)
SYNONYMS AND THEIR COMMON NAMES
SR NO SYNONYM COMMON NAME

1 Rochelle salt Sodium Potassium Tartarate
2 Dakin’s solution Sodium Hypochloride
3 Glaubers salt Sodium Sulphate
4 Epsom salt Magnesium Sulphate

5 China clay Heavy Kaolin

6 Gypsum Calcium Sulphate
7 Calomel Mercurous Chloride
8 Soap clay Bentonite
9 French chalk Talc
10 Alum Potassium Aluminium Sulphate
11 Hypo Sodium Thiosulphate
12 Precipitated chalk Calcium Carbonate
13 Slaked lime Calcium Hydroxide
14 Bleaching powder Chlorinated Lime
15 Burrows solution Aluminium Acetate Solution
16 Laughing gas Nitrous Oxide
17 Tear gas (CS gas) Chlorobenzylidine Malononitrile
18 Iodine tincture Weak Iodine Solution
19 knock out drops Chloral Hydrate
20 Washing soda Sodium carbonate
21 Baking soda Sodium bicarbonate
22 Costic soda Sodium hydroxide
23. Lugols solution Aqueous Iodine Solution
VACCINES
LIVE ATTENUATED: INACTIVATED RECOMBINANT:

MEASLES RABIES HEPATITIS B
MUMPS INFLUENZA
POLIO TETANUS TOXOID:

RUBELLA HEPATITS A DIPTHERIA
TYPHOID TETANUS
VARICELLA
TUBERCULOSIS
YELLOWFEVER

TEST ORGANISM FOR MICROBIOLOGICAL ASSAY OF ANTIBIOTIC
SR NO ANTIBIOTIC TEST ORGANISM
1 Amikacin Staphlococcus aureus
2 Amphotericin B Saccharomyces cerevisiae
3 Bacitracin Micrococcus luteus
4 Bleomycin Mycobacterium smegmatis
5 Carbenicillin Pseudomonas aeruginosa
6 Doxycycline Staphlococcus aureus
7 Erythromycin Micrococcus luteus
8 Framycetin Bacillus pumilis , staphylococcus aureus
9 Gentamycin Staphylococcus epidermidis
10 Kanamycin Bacillus pumilis, staphylococcus aureus
11 kanamycin B Bacilus subtilis
12 Neomycin Staphlococcus epidermidis
13 Novobiocin Staphlococcus epidermidis
14 Nystatin Saccharomyces cerevisiae
15 Oxyteracycline Bacillus cereus, staphylococcus aureus
16 Polymyxin B Bordetella bronchiseptica
17 Rifamycin Bacillus subtilis
18 Streptomycin Bacillus subtilis , klebsiella pneumoniae
19 Tetracycline Bacillus cereus, staphylococcus aureus
DISEASE ASSOCIATED WITH ALTERED NEUROTRANSMITTERS LEVELS IN BRAIN
SR NO DISEASE NEUROTRANSMITTERS LEVELS

1 Parkinsonism Decreased DOPAMINE in striatum
2 Schizophrenia Increased DOPAMINE levels

3 Depression Decreased NOREPINEPHRINE & 5-HT
4 Mania Decreased NOREPINEPHRINE & 5-HT

5 Hallucination Increased 5-HT
Decreased ACETYLCHOLINE & Destruction
6 Alzheimer’s
of Cholinergic Neurons
7 Athetosis Decreased GABA in Putamen
8 Chorea Decreased GABA in Caudate Nucleus
9 Amyotropic lateral sclerosis Decreased ACETYLCHOLINE
ENZYMES AND THEIR METAL COFACTORS
FE2+ CYTOCHROMEOXIDASE, CATALASE, PEROXIDASE
CU2+ CYTOCHROME OXIDASE
DNA POLYMERASE, CARBONIC ANHYDRASE,

ZN2 +
ALCOHOL DEHYDROGENASE
MG2 + HEXOKINASE, GLUCOSE 6 PHOSPHATE
MN2+ ARGINASE
K+ PYRUVATE KINASE
NI2+ UREASE
MO NITRATE REDUCTASE
SE GLUTATHIONE PEROXIDASE
MICROSOMAL ENZYMES INDUCERS AND INHIBITORS
MICROSOMAL ENZYME INDUCERS

ALCOHOL
CHLORALHYDRATE
CORTISONE

NICOTINE
PREDNISOSLONE
PHENYTOIN
CHLORDIAZEPOXIDE
IMIPRAMINE
PHENOBARBITAL
TESTOSTERONE
MICROSOMAL ENZYME INHIBITORS

ALLOPURINOL
ORAL ANTIDIABETICS
DISULFIRAM
METRONIDAZOLE
ORAL ANTICOAGULANTS
ANABOLIC AGENTS
CHLORAMPHENICOL
ISONIAZID
MONOAMINE OXIDASE INHIBITORS
CEMETIDINE
DISEASE DEFECTIVE ENZYME

ALBINISM - TYROSINE-3-MONO OXYGENASE
ALKAPTONURIA - HOMOGENTISATE1,2-DIOXYGENASE
GALACTOSE-1-PHOSPHATE IRIDYLYL
GALACTOSEMIA -
TRANSFERASE
HOMOCYSTINURIA - CYSTATHIONE B- SYNTHASE
PHENYLKETONURIA - PHENYLALANINE-4-MONO OXYGENASE
TAYSACHS DISEASE - HEXOSAMINIDASE A
HYPERVALINEMIA - VALINE TRANSAMINASE
ARGINOSUCCINIC - ARGINOSUCCINATE LYASE ACIDEMIA
KRABBES DISEASE - BETA GALACTOSIDASE

FABRYS DISEASE - ALPHA GALACTOSIDASE

NIEMANN PICK DISEASE - SPHINGOMYELINASE
FARBERS DISEASE - CERAMIDASE
GAUCHERS DISEASE - BETA GLUOSIDASE
DIAGNOSTIC TESTS
NAME OF DISEASE DIAGNOSTIC TESTS
1. VDRL TEST,
2. KAHN TEST,
3. WASSERMAN TEST
SYPHILIS
4. TREPONEMA IMMOBILIZATION TEST,
5. FLUROESCENT ANTIBODY-ABSORBED
SERUM TEST.
1. SCHICK TEST,
DIPTHERIA
2. ELEX TEST
T.B TUBERCULIN, MANTOUX TEST
LEPROSY LEPROMIN TSEST
TYPHOID OR ENETRIC FEVER WIDAL TEST
RHUMETOID ARTHRITIS ROSE WATER TEST
SMALL POX OUCHTERLONY
1. COLD HEMAGLUTINATION TEST,

PNEUMONIA 2. STREPTOCOCCUS MG
HEMAGLUTINATION TEST
BRUCELLOSIS- COOMBS TEST(OPSONIZATION TEST)
LYMPHOGRANULOMA
FREI TEST
VENERUM
TYPHUS FEVER- WEIL FELIX TEST

HEMOPHILLIUS- DUCREY TEST
SCARLET FEVER- DICK TEST
TO DETECT HUMAN CHORNIC

GONADOTROPHIN IN SERUM RADIO IMMUNO ASSAY(RIA)
OF WOMAN
BIOASSAYS OF DRUGS AND ITS EFFECT ON THE ANIMAL
ADRENALINE BP raising effects in spinal cats
NORADRENALINE BP raising effects in spinal cats
HISTAMINE Contraction of isolated guinea pig ileum
INSULIN Hypoglycemic convulsions in mice
ACETYLCHOLINE Contraction of isolated frog rectus muscle
D TC Rabbit head drop due to paralysis of neck muscles
DIGITALIS Death due to cardiac arrest in guinea pig
OXYTOCIN Contraction of guinea pig uterine muscles
ANDROGENS Growth copons comb
ADRENO CORTICO
Adrenal ascorbic acid estimation in hypophysectomised rats
TROPIC HORMONE
MICRO ORGANISMS USED AS BIOASSAYS FOR VITAMINS
ASSAY MICRO ORGANISM VITAMIN
BIOTIN,
FOLICACID,
Lactobacillus casei
PYRIDOXAL,
RIBOFLAVINE

CALCIUM PANTOTHENATE,
L. Arabinosus
NICOTINIC ACID
L.leichmanii CYANOCOBALAMIN
L.viridans THIAMINE
Saccharomyces urarum INOSITOL
Acetobacter suboxydans PANTHOTHENOL
Neurospora crassa (or) s.carlsberginsis PRIDOXINE
BIOLOGICAL INDICATORS
Moist heat sterilisation (121 degre Centi ) Bacillus stearo thermophilus
Dry heat sterilisation (160 degre centi) Bacillus subtilis var niger
Hydrogen peroxide and peracetic acid Bacillus stearo thermophilus
Ethylene oxide , formaldehyde Bacillus subtilis var niger
Ionising radiation Bacillus pumilis
TESTS AND THEIR USES
SR NO TEST IDENIFY
1 Watson Schwartz Test Urobilinogen
2 Schumms Test Heme
3 Carrprice Test Vit A
4 Gmelins Test Bile Pigments
5 Gothlin Test Scurvy
6 Gofmann Test Serum Cholesterol
7 Murexide Test Uric Acid
8 Reinsch Test Heavy Metals

9 Gordons Test Spinal Fluid
10 Biuret Test Peptides

11 Legals Test For Estimation Of Acetone
12 Ames Test Carcinogenicity
SHORT CUTS FOR GPAT AND NIPER (EASY TO REMEMBER)
Busulfan feature: ABCDEF

 Alkylating agent
 Bone marrow suppression
 CML Indication
 Dark skin(hyperpigmentation)
 Endocrine insufficiency(adrenal)
 Fibrosis
Drugs causing Torsades de Pointes: APACHE

 Amiodarone
 Procainamide
 Arsenium
 Cisapride
 Haloperidol
 Erythromycin
Morphine side effects: MORPHINE

 Myosis
 Out of It (sedation)
 Respiratory depression
 Pneumonia(aspiration)
 Hypotension
 Infrequency (constipation,urinary retention)
 Nausea
 Emesis
Aspirin side effects: ASPIRIN

 Asthma
 Salicylism

 Peptic ulcer disease/phosphorylation-oxidat
 ion uncoupling/platelet disaggregation
 Intestinal blood loss
 Reye's Syndrome
 Idiosyncracy
 Noise(tinnitus)
SSRIs side effects: SSRI

 Seratonin syndrome
 Stimulate CNS
 Reproductive disfunction in male
 Insomnia
Inhalation anesthetics: SHINE

 Sevoflane
 Halothane
 Isoflurane
 Nitrous oxide
 Enflurane
Teratogenic drugs:"Win Teratogenic

 Warfarin
 Thalidomide
Epileptic drugs:
 Phenytoin,
 Valproate,
 Amazepine
 Retinoid
 ACE inhibitor
Third element: Lithium

Gynaecomastia causing drugs: DISCOS
 Digoxin
 Isoniazid
 Spironolactone
 Cimetidine
 Oestrogens
 Stilboestrol

Methyldopa Side effects: METHYLDOPA

 Mental retardation
 Electrolyte imbalance
 Tolerance
 Headache/ Hepatotoxicity
 Psychological upset
 Lactation in female
 Dry mouth
 Oedema
 Parkinsonism
Antirheumatic agents: CHAMP

 Cyclophosphamide
 Hydroxycloroquine and choloroquinine
 Auranofin and other gold compounds
 Methotrexate
 Penicillamine
Phenytoin: adverse effects PHENYTOIN

 P-450 interactions
 Hirsutism
 Enlarged gums
 Nystagmus
 Yellow-browning of skin
 Teratogenicity
 Osteomalacia
 Interference with B12 metabolism (hence anemia)
 Neuropathies: vertigo, ataxia, and headache
Sodium Valproate side effccts VALPROATE

 Vomiting
 Alopecia
 Liver toxicity
 Pancreatitis/ Pancytopenia

 Retention of fats (weight gain)
 Oedema (peripheral oedema)
 Appetite increase
 Tremor
 Enzyme inducer (liver)
Amiodarone: action, side effects: 6 P's:

 Prolongs action potential duration
 Photosensitivity
 Pigmentation of skin
 Peripheral neuropathy
 Pulmonary alveolitis and fibrosis
 Peripheral conversion of T4 to T3 is inhibited -> hypothyroidism
Antiparkinson Drugs: SALAD

 Selegiline
 Anticholinenergics (trihexyphenidyl, benzhexol, ophenadrine)
 L-Dopa + peripheral decarboxylase inhibitor (carbidopa, benserazide)
 Amantadine
 Dopamine postsynaptic receptor agonists (bromocriptine, lisuride, pergolide)
Therapeutic Index Formula TILE

TI = LD / ED
Anti epeleptic drugs Dr.BHAISAB's New PC.

 Deoxy barbiturates
 Barbiturates
 Hydantoin
 Aliphatic carb acids
 Iminostilbenes
 Succinimides
 BZD's
 Newer drugs

 Phenyltriazines
 Cyclic GABA analogues
Adverse effects of Tetracyclines-KAPIL DEV

 Kidney toxicity
 Antianabolic effect
 Phototoxicity
 Liver toxicity
 Diabetes insipidus
CAPTOPRIL Side effects CAPTOPRIL

 Cough Angioedema
 Agranulocystosis
 Proteinuria/ Potassium excess
 Taste changes
 Orthostatic hypotension
 Pregnancy contraindication/ Pancreatitis/ Pressure drop (first dose hypertension)
 Renal failure (and renal artery stenosis contraindication)/ Rash
 Indomethacin inhibition
 Leukopenia/Liver toxicity
Lithium: side effects LITH

 Leukocytosis
 Insipidus [diabetes insipidus, tied to polyuria]
 Tremor/ Teratogenesis
 Hypothyroidism
Myocardial Infarction (MI): signs and symptoms PULSE

 Persistent chest pains
 Upset stomach
 Lightheadedness
 Shortness of breath
 Excessive sweating

MI: basic management BOOMAR

 Bed rest
 Oxygen
 Opiate
 Monitor
 Anticoagulate
 Reduce clot size
Treatment of Heart Failure: ABCDE

 ACE inhibitors
 Beta-blockers
 Calcium channel blockers
 Diuretics
 Endothelin-converting enzyme inhibitors
Essential Amino acids

My True Love Is Throug Valentine Love Phrases
 Methionine
 Threonine
 Leucine
 Isoleucine
 Tryptophan
 Valine
 Lysine
 Phenyl alanine
BLOOD GROUP AND ITS COLOR OF LABEL MOST IMP
BLOOD GROUP COLOR OF LABEL
O BLUE
A YELLOW
B PINK
AB WHITE

ABBREVIATIONS IMP FOR GPAT AS WEL AS IN NIPER

Description of some Important Abbreviations:-
ABBREVIATIONS FULL FORM
AAAS American Association of Advancement of Science
AALAS American Association for Laboratory Animal Science
AIOPI Association of Information Officers of the Pharmaceutical Industry
ALF American Liberation Front
ANDA Abbreviated New Drug Application
BEA Breeding for Experimental Animals
BINAS Biosafety Information Network and Advisory Service
BMA British Medical Association
BMJ British Medical Journal
BPC Bulk Pharmaceutical Chemicals
BPI British Pharmaceutical Index
BrAPP British Association of Pharmaceutical Physicians
BUAV British Union for the Abolition of Vivisection
CADD Computer Aided Drug Design
CDC Centre for Disease Control
CIOMS Council for International Organisations of Medical Sciences
Committee for Purpose of Control & Supervision of Experimental
CPCSEA
Animals
CPI Consumer Price Index
CRA Clinical Research Associate
CRC Clinical Research Council
CRF Case Report Form
CRN Clinical Research Network
CRO Contract Research Organisation
CSM Committee on Safety of Medicines
CTA Clinical Trial Authorisation (formerly the CTX, CTC, DDX)
CTC Clinical Trial Certificate (Now CTA)
CTC Clinical Trials Centre

CTD Common Technical Document

CTD Common Technical Document
CTX Clinical Trial Exemption (Now CTA)
DRA Drug Regulatory Affairs
DUMP Disposal of Unwanted Medicines and Poisons
EFPIA European Federation of Pharmaceutical Industries & Associations
EMEA European Medicine Agency
FDA Food & Drug Administration
FIP International Pharmaceutical Federations
GCP Good Clinical Practices
GLP Good Laboratory Practices
GMP Good Manufacturing Practices
Generic term for good practice requirements in the Pharmaceutical
Gxp
industry
HIS Indian Health Services
HPLC High Performance Liquid Chromatography
HRSA Health Resources & Service Administration
IACUC Institutional Animal Care and Use Committee
IAES Institutional Animal Ethics Committee
ICDRA International Conference for Drug Regulatory Authorities
International Conference on Harmonization of technical requirement
ICH
for registration of pharmaceuticals
IIG Inactive Ingredient Guide
Investigational Medicinal Products IMP - Investigational Medicinal
IMP
Products
IMPD Investigational Medicinal Product Dossier
INDA Investigational New Drug Application
INN International non-proprietary names (for pharmaceutical substances)
International Drug Information System - the previous WHO adverse
INTDIS
reactions database
IPC Indian Pharmaceutical Congress

IPGA Indian Pharmacy Graduate Association

ISO International Organization for Standardization
ISoP International Society of Pharmacovigilance
ISPE International Society for Pharmacoepidemiology
MedDRA Medical Dictionary for Drug Regulatory Affairs
National Agency for Food and Drug Administration and Control,
NAFDAC
Nigeria
NCPA National Community of Pharmacist Association
NCPO National Conference of Pharmaceutical Organisations
NDA New Drug Application
NDMS National Disaster Medical System
NME New Molecule Entity
NSAID Non-Steroidal Anti-Inflammatory Drug
OTC Over-The-Counter
PDS Pharmacoepidemiology and Drug Safety (journal)
PEM Prescription Event Monitoring
PHRMA Pharmaceutical Research and Manufacturers Association
PIL Package Insert Leaflet
PMDA Pharmaceuticals and Medical Devices Agency, Japan
PMS Post-Marketing Surveillance
POM Prescription Only Medicine
PSM Procurement and Supply Management
PSUR Periodic Safety Update Report
QA Quality Assurance
QSM-WHO Quality Assurance and Safety of Medicines (WHO)
R&D Research and Development
RAPS Regulatory Affairs Professionals Society
RCT Randomised Clinical Trials
RDE Remote Data Entry
RDS Research Defence Society
REC Research Ethics Committee

RGN Registered General Nurse

RPSGB Royal Pharmaceutical Society of Great Britain
RSM Royal Society of Medicine
Rx Prescription (YOU TAKE)
SARS Severe Acute Respiratory Syndrome
SCDM Society for Clinical Data Management
SIDS Sudden Infant Death Syndrome
SIGAR Special Interest Group on Adverse Reactions
TGA Therapeutic Goods Administration, Australia
TMF Trial Master File
TUFAM General Directorate of Pharmaceuticals and Pharmacy, Turkey
UDV Unit Dose Vial
UKECA United Kingdom Ethics Committee Authority
USP United States Pharmacopoeia
WIPO World Intellectual Patent Office
SCHEDULES TO THE RULES
SCHEDULES THE RULES
Perform for application for the licences, issues and renewal of licences, for
A
sending memoranda under the Act.
Rates of fee for test or analysis by the Central Drugs Laboratory or the
B
Government analysist.
List of biological and other special products whose import, sale, distribution
C
and manufacturing are a governed by special provision.
List of other special products whose import, sale, distribution and

C1
manufacturing are governed by special provision.
D List of drugs exempted from the provisions of import of drugs.
List of poisionous substances under the Ayurvedic (including Sidha) and

E1
Unani systems of medicine.

Provisions applicable to the production, testing, storage, packing and

F & F1
labeling of biological and other Special products.
F2 Standards for surgical dressings.
F3 Standards for sterilized umbilical tapes.
FF Standards of ophthalmic preparations.
List of substances that are required to be used only under medical

G
supervision and which are to be labeled accordingly.
H List of prescription drugs.
J Disease or ailments which a drug may not purport to prevent or cure.
K Drugs exempted from certain provision relating to manufacture of drugs.
M GMP requirement of factory premises, plants and equipment.
Requirement of factory premises etc. for manufacture of homoeopathic

M1
preparation.
M2 Requirement of factory premises etc. for manufacture of cosmetics.
N List of minimum equipment for efficient running of a pharmacy.
O Standard for disinfectant fluid.
P Life period of drug.
Q List of coals tar color permitted to be used in cosmetics.
R Standard for mechanical contraceptive. CONDOMS
S Standard for cosmetics.
Requirement of factory premises and hygienic condition for Ayurvedic

T
(including Sidha) and Unani drugs.
Particulars to be shown in manufacturing, raw material and analytical

U
records of drug.
Particulars to be shown in manufacturing, raw material and analytical

U1
records of cosmetics.
V Standard for patent or proprietary medicines.
W List of drug which is to be marketed under generic names only.

List of drugs whose import, manufacture and sale, labeling and packaging
X
are governed by special provision.
Requirement and guideline on clinical trials for import and manufacture of

Y
new drug.
BETA BLOCKERS
Comparative information Pharmacological differences

Agents with intrinsic sympathomimetic action (ISA)
 Acebutolol,
 Carteolol,
 Celiprolol
 Mepindolol
 Oxprenolol
 Pindolol
Agents with greater aqueous solubility (hydrophilic beta blockers)

 Atenolol
 Celiprolol
 Nadolol,
 Sotalol
Agents with membrane stabilizing effect

 Acebutolol,
 Betaxolol,
 Pindolol,
 Propranolol
Agents with antioxidant effect

 Carvedilol,
 Nebivolol
INDICATION DIFFERENCES
Agents specifically indicated for cardiac arrhythmia
 Esmolol,
 Sotalol,
 Landiolol

Agents specifically indicated for congestive heart failure

 Bisoprolol,
 Carvedilol,
 Sustained-release metoprolol,
 Nebivolol
Agents specifically indicated for glaucoma

 Betaxolol,
 Carteolol,
 Levobunolol,
 Metipranolol,
 Timolol
Agents specifically indicated for myocardial infarction

 Atenolol,
 Metoprolol,
 Propranolol
Agents specifically indicated for migraine prophylaxis

 Timolol,
 Propranolol
Propranolol is the only agent indicated for control of tremor, portal hypertension, and
esophageal variceal bleeding, and used in conjunction with α blocker therapy in
phaeochromocytoma.
SOME IMP PH VALUE
Blood: 7.4
Tear 7.2
Skin 7.4
Secretion of Skin: 5.5
Gastric juice: Infants: 5, Adults: 2
Saliva: 6.3-6.7
Urine: 4.4-8

Stool: approx. 6
Bile Juice: 8-8.6
Semen: 7.2-8
Vagina: 3.8-4.5
MECHANISM OF ACTION
1-DNA Dependent RNA Polymerase- Rifampcin

2- RNA Dependent DNA Polymerase- Zidovudine
3-Proetin Synthesis Blocker- Erythromycin, Chloramphenicol & Tetracycline
4-ACE Inhibitor- Captopril
5-Ca Channel Blocker- Nifedipine, Diltiazem
6-COX Inhibitor- Asprin
7-GABA Facilitator- Benzodiazepines
8-Antimetabolites- Methotrexate
9-Loop Diuretics- Frusemide
10-High Ceiling Diuretics- Spironolactone
11-Alteration of bacterial DNA- Choloroquine
12-Inhibition of Viral replication- Amantidine, Acyclovir
13-H1 blocking agent- Mepyramine, Loratadine
14-H2 Blocking agent- Rantidine, Cimetidine, Famotidine, Cyprohaptidine
15-Proton Pump inhibitor- Omeprazole
16-DNA Metabolism Inhibitors- Quinacrine (Mepacrine)
17-Spindle Poison- Vinca, Griesofulvin
18-Folic acid synthesis inhibitor- DDS
19-GABA Inhibitor- Sodium Valproate
20-DNA Synthesis Prevention – Nalidixic Acid
21-Prostaglandin Synthesis Inhibition- Oxyphenbutazone, Ibuprofen
22-Mycolic acid synthesis inhibition- INH
23-Folic acid antagonist- MTX, PAS, DDS & Primethamine
24-Desruption of DNA structure- MNZ
25-Inhibition of cell wall synthesis- Beta lactam antibiotics (penicillin)
26-Release of nor epinephrine- Ephedrine
27-Ergosterol Biosnythesis Inhibitors- Clotrimazole, Miconalzole, Ketoconazole

28-Ach esterase inhibitors- Physostigmine, Neostigmine, Edrophonium, Metrifonate

29-Reverse Transcriptase Inhibitors- Stavudine, zidovudine
30-Inhibition of HIV Protease- Amepranavir
31-DNA Gyrase Inhibitor- Cinoxacin
32-Inhibition of DNA Polymerase-Gossypol
33-NMDA Receptor Antagonist- Amantadine, Ketamine, Dextromethorphan, Memantine &
Nitrous Oxide
34-DNA intercalating agent- Daunorubicin, Doxorubicin, Ellipticin & Ethidium Bromide
35-Antim mitotic agent- Amphethenile
36-Alkylating agent- Thiotepa
37-Alpha receptor antagonist- Phentolamine
38-Beta receptor antagonist- Propanolol, Aplrenolol
39-Alpha receptor agonist- Norepinehrine
40- Beta receptor agonist- Isoproterenol & Salbutamol
41-DNA Adduct Formation- Procarbazine
42-Carbonic anhydrase inhibitor- Acetazolamide
43-Phosphodiestrase Inhibitor- Theophylline
44-Thrombin action prevention- Heparin
45-Xanthine oxidase inhibitor- Allopurinol
46-Cholinergic Blockade- Ipratropium
47-Adenosine Deaminase inhibitor- Crisnatapase
48-Immunomodulation- Imiquimod
49-Amino acid transfer interference- Econazole
50-Mast Cell Stabilization- Ketosifen
MUST DO THIS TABLE IMP FROM JURI
SR NO ORGANISATION LOCATION
1 BCG Vaccine Lab Chennai
2 Central drug testing lab (CDTL) Mumbai
3 Central drug Laboratory (CDL) Kolkata
4 Central Drug Research Institute (CDRI) Lucknow
5 Central Research Institute (CRI) Kasauli

6 Indian Drug Manufactures Association (IDMA) Mumbai
7 Indian Society of Blood Trensfusion & Immunoheamatology Pune
8 Indian Veterinary Research Institute (IVRI) Izatnagar
9 Central Indian Pharmacoepia Laboratory (CIPL) Ghaziabad
10 National Plasma Fractionation Centre (NPFC) Mumbai
11 National Institute for Communicable Disease (NICD) New Delhi
12 Indian Institute for Virology (IIV) Pune
13 Organization of Pharmaceutical Procedures Mumbai
14 Dabur Research foundaion Ghaziabad
15 Institute of applied man power research New Delhi
16 CD Testing Lab Mumbai
17 Synthetic Drug Plant Hyderabad
18 National Institute of Nutrition (NIN) Hyderabad
19 National Brain Research Institute (NBRI) Manesar (Gurgaon)
IMPORTANT PHARMACOLOGICAL TERMS:
•Antagonism
–The opposition between 2 or more medications ex. narcotics and Naloxone
•Bolus
–A single, often large dose of a drug. Often the initial dose
•Cumulative action
–An increased effect caused by multiple doses of the same drug. Caused by buildup in the
blood.
•Hypersensitivity
–A reaction to a drug that is more profound than expected and which often results in an
exaggerated immune response
•Idiosyncrasy
–A reaction to a drug that is significantly different from what is expected
•Indication
–The medical condition for which the drug has proven therapeutic value.

•Parenteral
–Any route of administration other than the digestive tract
•Pharmacodynamics
–Study of the mechanisms by which drugs act to produce biochemical or physiological
changes in the body
•Pharmacokinetics
–Study of how drugs enter the body, reach their site of action and are eliminated from the
body.
•Potentiation
–The enhancement of a drug’s effect by another drug
–Eg. Promethazine may enhance the effect of morphine; also alcohol and barbiturates
•Refractory
–The failure of a patient to respond as expected to a certain medication
•Synergism
–The combined action of 2 or more drugs that is greater than the sum of the 2 drugs acting
independently.
•Therapeutic Action
–The intended action of a drug given in an appropriate medical setting
•Therapeutic Threshold
–The minimum amount of a drug that is required to cause the desired response
•Therapeutic Index
–The difference between the therapeutic threshold and the amount of the drug considered to
be toxic
–Often referred to as Safe and Effective range.
•Tolerance
–The decreased sensitivity or response to a drug that occurs after repeated doses
–Increased doses are required to achieve the desired effect
• Untoward Effect
–A side effect of a drug that is harmful to the patient
STERILIZATION OF MEDIA
In almost all cases, once a medium is made, it must be treated to eliminate any
microorganisms contaminating containers, media ingredients, weighing papers, or other

surfaces that come in contact with the medium. If this is not performed correctly,
contaminates arise during incubation, making microbiological investigations impossible.
Sterilization is defined as the inactivation (or removal) of all life forms (including the pseudo-
life forms, viruses) in a specific area. Culture media must be made sterile without inactivating
nutrients necessary for growth of the microorganism. Equipment and media used in the
microbiology laboratory are most often sterilized using one of the methods outlined below.
Autoclaving - moist heat (121°C) under pressure (15-17 lb/in2)

Mode of action - coagulates proteins
Materials - heat stable items such as most culture media, glass and metal, but not plastics
Oven - dry heat (160°C for several hours)
Mode of action - coagulates proteins
Materials - glass and metals but not liquids nor plastics
Filtration - 0.22 to 0.45 µm pore size
Mode of action - prevents organisms from passing through the filter, but does allow viruses to
pass so therefore not sterilization in true sense.
Materials - Solutions of heat sensitive compounds such as some amino acids, vitamins,
sugars etc.
Radiation - ultraviolet light or gamma rays
Mode of action - damages nucleic acids
Materials - heat sensitive solids such as plastics, however effective on surfaces only
Gas - ethylene oxide
Mode of action - inactivates enzymes
Materials - heat sensitive solids such as some plastics.
Temperature Relationships
Microorganisms as a whole, are able to grow at a tremendous range of temperatures. Bacteria
have been discovered growing near the Galopagos trench (a marine ocean vent) at
temperatures of 110°C and in super-cooled foods as low as -12°C. The temperature range that
a specific microorganism is able to grow at is thought to be limited by the activity of its
enzymes and the fluidity of the membrane. Extreme temperatures either prevent enzymes
from carrying out their reactions quickly enough (at low temperatures) or denature
(inactivate) enzymes (at high temp and sometimes low temperatures). It is also possible that
temperature has its effect by interfering with the fluidity of membranes, too fluid at high

temperatures, frozen at low temperatures. Overly fluid membranes cannot maintain their
intergrety and leak, frozen membrane cannot perform vital functions such as electron
transport.
Microbes can be classified by their optimum temperature for growth.
Organisms having an optimum of <20°C are termed Psychrophiles.
Those that grow optimally from 20 to 45°C are called Mesophiles.
Microorganisms that have temperature optima of >45°C are termed Thermophiles.
It is possible for an organisms to have an optimum temperature in one classification, but be

capable of growing at temperatures much above or below the optimum. For
example, Bacillus coagulans is capable of growth at mesophillic temperatures, but will also
grow at temperatures of 55-60°C. These organisms are termed facultative thermophiles.
Microorganisms will cease to grow below their optimum temperature, but frequently will
survive in an inert state. In fact refrigeration or freezing of bacteria can have a preservative
effect. Most microorganisms are killed above the optimum temperature
SOME IMPORTANT NOTES FOR GPAT AND NIPER EXAM
Partition Coefficient:
OCTANOL: water partition coefficient often used in formulation development.
Q10 Method of Shelf Life Estimation:
Shelf life estimation
Q10 = e {(Ea/R) [(1/T + 10) – (1/T)]}
Arrhenius Equation: log = k2\k1 = Ea (T2 – T1)\ 2.3 RT1T2
Shelf Life Estimates:

Q10 = [K (T+10)]/KT =e [(Ea /R) ({1/T+10} {1/T}]
Q10 = 2 Lower limit

Q10 = 3 Average, best estimate
Q10 = 4 Upper limit

t90 Equation for Shelf Life Estimates:

t90 (T2) = t90 (T1)/Q10 (Delta T/10).
Note: A “+” Delta T decreases shelf life and a “-” Delta T increases shelf life.
Sweetening Agents:
 Dextrose
 Mannitol
 Saccharin
 Sorbitol
 Sucrose
Preservative Utilization:
 •Benzoic acid/sodium benzoate
 •Alcohol
 •Phenylmercuric nitrate/acetate
 •Phenol
 •Cresol
 •Chlorobutanol
 •Benzalkonium chloride
 •Methyl paraben/propyl paraben
 •Others
Preservatives may be used alone or in combination to prevent the growth of
microorganisms.
Alcohols
Ethanol is useful as a preservative when it is used as a solvent. It needs a relatively high
concentration (> 10%) to be effective.
Propylene glycol also used as a solvent in oral solutions and topical preparations. It can
function as a preservative in the range of 15 to 30%. It is not volatile like ethanol.
Acids
 Benzoic acid and sorbic acid have low solubility in water.
 They are used in a concentration range from 0.1 % to 0.5%.
 Only the non-ionized form is effective and therefore its use is restricted to
preparations with a pH below 4.5.

Esters
Parabens are esters (methyl, ethyl, propyl and butyl) of p-hydroxybenzoic acid.
 They are used widely in pharmaceutical products
 They are effective and stable over a pH range of 4 to 8.
 They are employed at concentrations up to about 0.2%.
 Frequently 2 esters are used in combination in the same preparation.
 To achieve a higher total concentration
 To be active against a wider range of microorganisms.
Quaternary Ammonium Compounds

 Benzalkonium chloride is used at a relatively low concentration 0.002 to 0.02%.
 This class of compounds has an optimal activity over the pH range of 4 to 10 and is
quite stable at most temperatures.
 Because of the cationic nature of this type of preservative it is incompatible with
many anionic compounds.
Antioxidants
Vitamins, essential oils & almost all fats and oils can be oxidized.
Oxidation reaction can be initiated by:
1. Heat: maintain oxidizable drugs in a cool place
2. Light: use of light- resistant container
3. Heavy metals (e.g. Fe, Cu): effect of trace metals can be minimized by using citric acid or
ethylenediamine tetraacetic acid (EDTA) i.e. sequestering agent.
Antioxidants as propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite,
ascorbic acid (vit. C) Can be used.
•SWEETENING AGENTS
Sucrose is the most widely used sweetening agent.

Advantages: Colourless, highly water soluble, stable over a wide pH range (4-8), increase the
viscosity, masks both salty and bitter taste, has soothing effect on throat.
Polyhydric alcohols (sorbitol, mannitol and glycerol) possess sweetening power and can be
used for diabetic preparations.
Humectants: such as glycerin and sorbitol (5-20% in MW)

 Increase the viscosity of the preparation

 Enhance the sweetness of the product
 Improve the preservative qualities of the product.
Surfactants: Non-ionic and anionic surfactants aid in the solubilization of flavors and in the
removal of debris by providing foaming action. Cationic surfactants such as
cetylpyridinium chloride are used for their antimicrobial properties, but these tend to impart
a bitter taste.
Flavours: are used in conjunction with alcohol and humectants to overcome disagreeable
tastes. The principle flavoring agents are peppermint, cinnamon, menthol or methyl
salicylate.
Otic Solutions:
The main classes of drugs used for topical administration to the ear include local anesthetics,
e.g.: benzocaine; antibiotics e.g.; neomycin; and anti-inflammatory agents, e.g.; cortisone.
Polyols (e.g. glycerin or sorbitol) may be added to
- retard crystallization of sucrose or increase the solubility of added ingredients.
Invert sugar
D is more readily fermentable than sucrose
D tend to darken in color
C retard the oxidation of other substances.
The levulose formed during inversion is sweeter than sucrose; therefore the resulting syrup is
sweeter than the original syrup.
When syrup is overheated it caramelizes.

The sucrose in the 66.7% w/w solution must be at least 95% inverted.
MUCILAGES
The official mucilages are thick viscid, adhesive liquids, produced by dispersing gum (acacia
or tragacanth) in water.
Mucilages are used as suspending agents for insoluble substances in liquids; their colloidal
character and viscosity prevent immediate sedimentation.
Synthetic agents e.g. carboxymethylcellulose (CMC) or polyvinyl alcohol are
nonglycogenetic and may be used for diabetic patients.

ELIXIRS
Are clear, pleasantly flavored, sweetened hydroalcoholic liquids intended for oral use.
They are used as flavors and vehicles
E.g. Dexamethasone Elixir USP and Phenobarbital Elixir USP.
COLLODIONS:
Are liquid preparations containing pyroxylin (a nitrocellulose) in a mixture of ethyl ether and
ethanol
Rubefacient
A substance for external application that produces redness of the skin e.g. by causing dilation
of the capillaries and an increase in blood circulation.
Counterirritant
A medicine applied locally to produce superficial inflammation in order to reduce deeper
inflammation.
Effervescent tablet:
contain acid substances (citric and tartaric acids) and carbonates or bicarbonates and
which react rapidly in the presence of water by releasing carbon dioxide.
Oxymels: These are preparations in which the vehicle is a mixture of acetic acid and honey.
Magnesium sulphate: Magnesium cause smooth muscle relaxation secondary to inhibition

of calcium uptake.
Atopy is strongest predisposing factor for developing asthma.
Asthma is a chronic inflammatory disorder of the airways in which many cells &
cellular elements play a role
(Mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, & epithelial cells).
Child-onset asthma
–Associated with Atopy
–IgE directed against common environmental antigens
(House-dust mites, animal proteins, fungi

–Viral wheezing Infants/children, allergy/allergy history associated with continuing

asthma through childhood.
Leukotriene modifiers:
 Zafirlukast - leukotriene receptor antagonist
 Zileuton - 5-lipoxygenase inhibitor is alternative therapy to low doses of inhaled
steroids/nedocromil/cromolyn. 5-lipoxygenase inhibitor

Long-acting beta2-agonists (LABA)
Beta2-receptors are the predominant receptors in bronchial smooth muscle Stimulate ATP-
cAMP which leads to relaxation of bronchial smooth muscle and inhibition of release of
mediators of immediate hypersensitivity Inhibits release of mast cell mediators such as
histamine, leukotrienes, and prostaglandin-D2. Beta1-receptors are predominant receptors in
heart, but up to 10-50% can be beta2-receptors.
Long-acting beta2-agonists (LABA)
 Salmeterol (Serevent)
 Salmeterol with fluticasone (Advair).
 Albuterol
DRUGS AND SCHEDULE
Schedule I
Drugs in this schedule have a high abuse potential (narcotic and hallucination effects).
Examples are heroin, marijuana.
Schedule II
Drugs in this schedule have a high abuse potential with severe psychic or physical
dependence liability. Included are certain narcotic analgesics, stimulants, and depressant
drugs. Examples are opium, morphine, codeine, hydromorphone, methadone, meperidine,
oxycodone, anileridine, cocaine, amphetamine, methamphetamine, phenmetrazine,
methylphenidate, amobarbital, pentobarbital, secobarbital, methaqualone, and phencyclidine.
Schedule III
Drugs in this schedule have an abuse potential less than those in Schedules I and II and
include compounds containing limited quantities of certain narcotic analgesic drugs, and
other drugs such as barbiturates, glutethimide, methyprylon, and chlorphentemine. Any
suppository dosage form containing amobarbital, secobarbital, or pentobarbital is in this
schedule.

Schedule IV
Drugs in this schedule have an abuse potential less than those listed in Schedule III and
include such drugs as barbital, phenobarbital, chloral hydrate, ethchlorvynol, meprobabmate,
chlordizepoxide, diazepam, oxazepam, chloroazepate, flurazepam, etc.
Schedule V
Drugs in this schedule have an abuse potential less than those listed in Schedule IV and
consist primarily of preparations containing limited quantities of certain narcotic analgesic
drugs used for antitussive and antidiarrheal purposes.
SOME IMP PONTS FROM PHARMACEUTICS
Creams – semisolid emulsion systems (o/w, w/o) containing more than 10% of water.
Pastes – semisolid dispersion system, where a solid particles (> 25%, e.g. ZnO) are
dispersed in ointments – mostly oleaginous (Petrolatum).
Antioxidants which act by providing electrons and easily available hydrogen atoms that
acceptable more readily by the free radicals (atoms containing one or more unpaired
electrons as molecular oxygen O-O or free hydroxyl group (OH)
Examples of Antioxidants: Na2SO3, NaHSO3, H3PO2 and Ascorbic
In oligeanous preparation –
 Alpha tocopherol,
 BHA (butylhydroxyanisole),
 BHT (butyl hydroxytoluene)
 Ascorbic palmitate.
EXAMPLES:
Epinephrine preparations - Adrenergic - do not use the if it is brown or contains precipitate
Nitroglycerin Tablets - Antianginal - to prevent loss of potency, keep these tablets in the
original container
Paraldehyde - Hypnotic - subject to oxidation to form acetic acid.
POLYMORPHISM:
Important factor on formulation is the crystal or amorphous from of the drug substance.
The amorphous form of a compound is always more soluble than a corresponding crystal form.

The most widely used methods are hot stage microscopy, thermal analysis, infrared
spectroscopy, and x-ray diffraction.
PROBABLE MODES OF ACTION OF SOME PRESERVATIVES
1. Benzoic acid, boric acid, p-hydroxybenzoates: Denaturation of proteins.

2. Phenols, chlorinated phenolic cmpds: lytic, denaturation action on cytoplasmic
membranes and for chlorinated preservatives, also by oxidation of enzymes
3. Alcohols: lytic and denaturation action on membranes.
Quaternary compounds: Lytic action on membranes.
4. Mercurials: Denaturation of enzymes by combining with thiol (-SH) groups.
Flavoring Agents
*** To mask effectively the unwanted or disagreeable taste of drugs
In general, low molecular weight are salty, like NaCl, KCl, NH4Cl, NaBr and higher
molecular salts are bitter except some lead salts.
Examples: Anise oil, Cinnamon, Peppermint, and Orange.
With organic compounds, an increase in the number of OH group seems to increase the
sweetness of the compound. Sucrose which has 8 OH groups is sweeter
than glycerin which has 3 OH groups.
SWEETENING PHARMACEUTICALS
SACCHARIN = metabolized and excreted by the kidneys virtually unchanged.
CYCLAMATE = metabolized or processed in digestive tract and it’s by product are excreted
by the kidneys.
ASPARTAME = breaks down in the body into three basic components: the amino
acids phenylalanine and aspartic acid, and methanol.
Because of its metabolism to phenylalanine, the use of aspartame by persons with phenylketonuria
(PKU) is discourages, and diet foods and drinks must bear appropriate label warning.
Saccharin and cyclamate were “Generally Recognized as Safe” or what is known as GRAS.
ACESULFAME = is more stable than aspartame at elevated temperature;

It is use in candy, chewing gum, confectionery, and instant coffees and teas.
STEVIA POWDER = Stevia Rebaudiana bertoni.
It is natural, nontoxic, safe, and about 30 times as sweet as cane sugar, or sucrose.

AESTHETIC VALUE
Liquid preparations - the amount is ranging from 0.0005 to 0.001% depending upon the
colorant and intensity desired Solid or powdered, Compressed Tablets - generally larger
proportion is required (0.1% Ointments, suppositories, opthalmic and parenteral -no
color additives)
DISSOLUTION APPRATUS IP AND USP
APPRATUS IP USP
Apparatus 1 Paddle (37º) Basket (37º)
Apparatus 2 Basket (37º) Paddle (37º)
Apparatus 3 Reciprocating Cylinder (37º) Reciprocating Cylinder (37º)
Apparatus 4 Flow-Through Cell (37 º) Flow-Through Cell (37 º)
Apparatus 5 Paddle over Disk (32º), Paddle over Disk (32º),
Apparatus 6 Cylinder (32º) Cylinder (32º)
Apparatus 7 Reciprocating Holder Reciprocating Holder
SOME IMP DRUG INTREACTION
S.N DRUG INTERACTION EFFECT
Aluminium Hydroxide Gel + Decrease effect of that drug due to

1 Pseudoephedrine increases pH of gastric fluid
2 Ciprofloxacin + Theophyline Increases plasma level of Theophyline
Aminoglycoside + beta- Lactam synergestic effect but if given in same

antibiotics syring it‘s become inactive due to
3
complex formation
4 Cortisone + Ampicillin= Antagonist

Erythromycin /Clarithromycin/ Increases level of Carbamazapine and

Telrithromycin + Carmazepam/ Phenytoin
5
Phenytoin =
Methotrexate + Sulfamethoxazole Displace from binding site and increases

6 free plasma concentration of drug
7 Amphotericin B + Flucytosine Synergestic effect
Ketoconazole + Amphotericin B Antagonized effect due to decreases

8 ergosterol level
9 Azoles ( including All) + Terbinafine Contraindicated
10 Posconazole + Ergot alkaloid Contraindicate
Cimetidine + Terbinafine increases plasma concentration of

11 Terbinafine
12 Gresiofulvin + Alcohol Potentiate toxicity of alcohol
13 Miconazole+ Warfarin inhibit metabolism of warfarin
14 MAO inhibitors + Pethidine Hyperpyrexia
15 TCA + SSRIs TCA toxicity
GOLD NUMBER & PROTECTION OF COLLOIDS
• Lyophilic sols are more stable than lyophobic sols.

• Lyophobic sols can be easily coagulated by the addition of small quantity of an electrolyte.
• When a lyophilic sol is added to any lyophobic sol, it becomes less sensitive towards
electrolytes. Thus, lyophilic colloids can prevent the coagulation of any lyophobic sol.
“The phenomenon of preventing the coagulation of a lyophobic sol due to the addition of
some lyophilic colloid is called sol protection or protection of colloids.”
• The protecting power of different protective (lyophilic) colloids is different. The efficiency
of any protective colloid is expressed in terms of gold number.

GOLD NUMBER
Zsigmondy introduced a term called gold number to describe the protective power of
different colloids.
This is defined as, “weight of the dried protective agent in milligrams, which when added to
10 ml of a standard gold sol (0.0053 to 0.0058%) is just sufficient to prevent a colour change
from red to blue on the addition of 1 ml of 10 % sodium chloride solution, is equal to the gold
number of that protective colloid.”
Thus, smaller is the gold number, higher is the protective action of the protective agent.
Protective power ∝ 1/Gold number
HYDROPHILIC SUBSTANCE GOLD NUMBER
Gelatin 0.005 - 0.01
Sodium oleate 0.4 – 1.0
Sodium caseinate 0.01
Gum tragacanth 2
Hamoglobin 0.03 – 0.07
Potato starch 25
Gum arabic 0.15 – 0.25
IMP YEARS LIST: USEFUL FOR GPAT & NIPER JEE
1935 RBI established

1949 RBI Nationalized
2005 RTI ACT
2005 Product Patent In India
1956 Companies Act
1932 Partnership Act
1993 End of GATT era
1997 National Pharmaceutical Pricing Authority (NPPA)
1994 Dolly sheep – First clone
1950 First Planning Commission
1984 Hatch-Waxman Act
1955 SBI nationalized

2005 IPC constituted

1896 First Olympics
2000 (26 Jan.) Human Genome Revealed
1970 Indian Patents Act
1919 Poison Act
1948 Pharmacy Act
1940 Drug and Cosmetic Act
1930 Dangerous Drug Act
1857 Opium Act
1954 Drug and Magic Remedies Act
1971 Medical Termination of Pregnancy Act (MTP)
1989 First ICH Indian pharmacopoeias:
1955 1st Edition IP
1966 2nd Edition IP
1985 3rd Edition IP
1996 4th Edition IP
2007 5th Edition IP
2010 6th Edition IP
2014 7th Edition IP
LIST OF WELL KNOWN POISONS & ANTIDOTES
POISONING ANTIDOTE USED

Paracetamol N-acetylcysteine
Anticoagulants (warfarin) Vitamin K
Opioids Naloxone
Iron (&other heavy metals) Desferrioxamine, Deferasirox or Deferiprone
Benzodiazepines Flumazenil
Ethylene glycol Ethanol or fomepizole, and thiamine, methanol -
ethanol or fomepizole, and folinic acid
Cyanide Amyl nitrite, Sodium nitrite and Sodium thiosulfate
Organophosphates Atropine and Pralidoxime

Magnesium Calcium Gluconate

Ca++ Cha. Blockers Vera, Dilti. CCB Calcium Gluconate
Beta-Blockers (Propranolol, Sotalol) Calcium Gluconate and/or Glucagon
Isoniazid Pyridoxine
Atropine Physostigmine
Thallium Prussian blue
Hydrofluoric acid Calcium Gluconate
Anticholinergics Cholinergics (&vice-versa)
SOME IMPORTANT FACTS GPAT NOTES

1. Lipid insoluble and water insoluble drugs are not absorbed from gut.
2. Most of the drugs are weakly acidic are weakly basic because stronger forms has high
ability to form corresponding ions.
3. Most (90%) of drugs absorbed through passive diffusion(non-ionic diffusion)
4. 0% protein binding – Lisinopril
5. 99% protein binding - oxyphenbutazone (metabolite of phenylbutazone)
6. To show an efficient drug action protien binding should be moderate, insufficient protein
binding shows less Vd & high protein binding lessens amount of drug at active site.
7. Extent of binding ----- albumin > acid glycoprotein > lipoprotein > globulins.
8. Drug having less Vd means its not bioavailable.(i.e decresed rate & amount of drug)
9. Bioavailability of Higher to Lower ------- parenteral > oral > rectal > topical.
10. Short acting barbiturates are due its rapid rate of distribution from brain.
11. Only unbounded drug (free form) undergoes metabolism.
12. The unbound drug 1st reaches liver from where it goes to other parts like kidneys
13. Only lipid soluble and non-ionic drugs can enters brain.
14. All orally administerd drugs undergo first pass metabolism.
15. Propanolol & Ca++ channel blockers have extensive first pass metabolism.
16. Mainly metabolism occurs to excrete the drug.
17. Acidic drugs are exerted at basic pH & vice-versa.
18. Absorption, Distribution, Elimination follows 1st order kinetics.
19. Drugs showing 0 order elimination kinetics are asprin, ethanol, phenytoin, Theophyline,
Tolbutamide, phenylbutazone, Warfarin, Heparin, salicylates etc.

20. Metabolism, Protein binding, carrier mediated transport at saturated conditions,

IV infusion IM implants, osmatic pumps undergo 0 order kinetics i.e rate or process
directly proportional to concentration or amount of reactants.
COUNTRY – CAPITAL – CURRENCY IMP FOR GPAT & NIPER JEE EXAM
COUNTRY – CAPITAL – CURRENCY
1. France – Paris – France
2. Germany – Berlin – Deutsche Mar
3. Greece – Athens – Drachma
4. Hong Kong - Victoria – Dollar
5. India - New Delhi – Rupee
6. Indonesia - Jakarta – Rupiah
7. Iran - Teheran – Rial
8. Iraq - Baghdad – Dinar
9. Ireland – Dublin – Pound
10. Italy - Rome – Lira
11. Japan – Tokyo – Yen
12. Kenya - Nairobi – Shilling
13. Malaysia - Kuala Lumpur – Ringgit
14. Nepal – Kathmandu – Rupee
15. New Zealand - Wellington – Dollar
16. Oman - Muscat – Rial
17. Pakistan – Islamabad – Rupee
18. Qatar – Doha – Riyal
19. Russia - Moscow – Ruble
20. Saudi Arabia – Riyadh – Rial
21. Singapore – Singapore City – Dollar
22. South Africa - Madrid – Rand
23. Spain – Madrid – Peseta
24. Sri Lanka - Colombo – Rupee
25. Sweden - Stockholm – Krona
26. Switzerland – Berne – France
27. Russia – Moscow – Ruble
28. Ukraine – Kiev – Hyrvnia

29. Azerbaijan – Baku – Ruble

30. Thailand – Bangkok – Baht
31. United Arab Emirates (UAE) – Abu Dhabi – Dirham
32. United Kingdom (UK)-London – Pound Sterling
33. United States of America (US) -Washington – Dollar
34. Yemen – Sana – Rial
35. Zimbabwe -Harare – Dollar
DRUGS BANNED IN INDIA
 Tetracycline liquid oral suspension
 Penicillin skin/eye ointement
 Methaquinone
 Oxytetracycline liquid oral preperations
 Demeclocycline liquid oral preperations
 Rosiglitazone
 Astemizole
 Terfinadine
DIFFERENT TESTS FOR CARBOHYDRATES
Name of test Use
Molisch test reducing sugars
Iodine test Starches
Benedicts reagent test Reducing sugars
Same like Molisch test but reduction carried in mild acidic

Barfords Test medium .to distinguish monosaccharide from disaccharides. -
reducing sugars.
Seliwanoffs Test Ketohexoses
Foulgers Test Ketohexoses
Rapid furfural test Ketohexoses
Osazone Test -
Sucrose hydrolysis test Sucrose

DIFFERENT TESTS FOR AMINO ACIDS AND PROTEINS
NAME OF TEST USE

Biuret reaction Two peptide linkage
Ninhydrin reaction Alfa amino acids
Xanthoproteic reaction Aromatic amino acids like, Phenylalanine, tyrosine, tryptophan
Milons reaction Phenolic amino acids (tyrosine )
Hopkins kole reaction Indole ring (tryptophan)
Sakaguchi reaction Guanidino group (arginine)
Nitroprusside reaction Sulfahydryl group (cysteine)
Sulfer test Sulfahydryl group (cysteine)

Pauly’s test Imidazole ring (histidine)
Folin coicateau’s test Phenolic group (tyrosine)
DIFFERENT TESTS FOR BIOCHEMICAL CONSTITUENTS OF BODY
NAME OF TEST USE/ DETECTION
Sodium hypobromide test Urea
Specific urease test Urea
Benedicts uric acid test Uric acid
Mureoxide test Uric acid (caffine, Theophyline etc.)
Jaffe’s test Creatinine
Benzatidine test Blood in urine etc.
Rothera test Ketone bodies
Hay’s rest Bile salt
Petterkofer’s test Bile salt
Gmelin test Bile pigments
Fouchets test Bile pigments

Folin wu method Blood glucose estimation
O-toulidine method Blood glucose estimation
Glucose –oxidase peroxidase (GOD-POD) Blood glucose estimation
Van den Bergh reaction Serum bilirubin
Henry-Caraways method Serum uric acid
Western blot TEST

confirmatory test for AIDS
MECHANISM OF ACTION
1- DNA Dependent RNA Polymerase- Rifampcin
2- RNA Dependent DNA Polymerase- Zidovudine
3-Proetin Synthesis Blocker- Erythromycin, Chloramphenicol & Tetracycline
4-ACE Inhibitor- Captopril
5-Ca Channel Blocker- Nifedipine, Diltiazem
6-COX Inhibitor- Asprin
7-GABA Facilitator- Benzodiazepines
8-Antimetabolites- Methotrexate
9-Loop Diuretics- Frusemide
10-High Ceiling Diuretics- Spironolactone
11-Alteration of bacterial DNA- Choloroquine
12-Inhibition of Viral replication- Amantidine, Acyclovir
13-H1 blocking agent- Mepyramine, Loratadine
14-H2 Blocking agent- Rantidine, Cimetidine, Famotidine, Cyprohaptidine
15-Proton Pump inhibitor- Omeprazole, ALL PRAZOLE
16-DNA Metabolism Inhibitors- Quinacrine (Mepacrine)
17-Spindle Poison- Vinca, Griesofulvin
18-Folic acid synthesis inhibitor- DDS
19-GABA Inhibitor- Sodium Valproate
20-DNA Synthesis Prevention – Nalidixic Acid
21-Prostaglandin Synthesis Inhibition- Oxyphenbutazone, Ibuprofen
22-Mycolic acid synthesis inhibition- INH

23-Folic acid antagonist- MTX, PAS, DDS & Primethamine

24-Desruption of DNA structure- MNZ
25-Inhibition of cell wall synthesis- Beta lactam antibiotics (Penicillin)
26-Release of nor epinephrine- Ephedrine
27-Ergosterol Biosnythesis Inhibitors- Clotrimazole, Miconalzole, Ketoconazole
28-Ach esterase inhibitors- Physostigmine, Neostigmine, Edrophonium, Metrifonate
29-Reverse Transcriptase Inhibitors- Stavudine, zidovudine
30-Inhibition of HIV Protease- Amepranavir
31-DNA Gyrase Inhibitor- Cinoxacin
32-Inhibition of DNA Polymerase-Gossypol
33-NMDA Receptor Antagonist-Amantadine, Ketamine, Dextromethorphan, Memantine &
Nitrous Oxide
34-DNA intercalating agent- Daunorubicin, Doxorubicin, Ellipticin & Ethidium Bromide
35-Antim mitotic agent- Amphethenile
36-Alkylating agent- Thiotepa
37-Alpha receptor antagonist- Phentolamine
38-Beta receptor antagonist- Propanolol, Aplrenolol
39-Alpha receptor agonist-Norepinehrine
40- Beta receptor agonist- Isoproterenol & Salbutamol
41-DNA Adduct Formation- Procarbazine
42-Carbonic anhydrase inhibitor- Acetazolamide
43-Phosphodiestrase Inhibitor- Theophylline
44-Thrombin action prevention- Heparin
45-Xanthine oxidase inhibitor- Allopurinol
46-Cholinergic Blockade- Ipratropium
47-Adenosine Deaminase inhibitor- Crisnatapase
48-Immunomodulation- Imiquimod
49-Amino acid transfer interference- Econazole
50-Mast Cell Stabilization- Ketosifen

DRUG & THEIR IMORTANT SIDE EFFECT
1. Grey Baby Syndrome- Chloramphenicol

2. Pin Point Pupil, Straubb's syndrome-Morphine
3. Reyes Syndrome- Asprin
4. Urine Coloration- Rifampcin
5. Frontal Headache- Indomethacin
6. Captopril- Persistant dry cough
7. Bleomycin-Pulmonary fibrosis
8. Vancomycin- Red man syndrome
9. Nicotinic acid- Flush
10. Steven Johnsons syndrome- Allopurinol, Sulphonamides, Itraconazole
11. sulphonamides-kernicterus
12. aminoglycosides-ototoxicity
13. Discolouration of teeth-tetracyclines
14. Doxorubucin & duanorubucin- cardiomyopathy.
15. Chloroquine- Cardiotixicity, retinopathy, discolouration of hair
16. Doxycycline- esophageal ulceration
17. Vincristin & Vinblastin- Neuropathy
18).cyclophosphamide- Alopecia, Pancretitis
19. Cimetidine & Spironolactone- Gynaecomastia
20. Jaurisch hexheimer reaction- Penicillin
21. Blue baby syndrome- Amiodarone
22. Nephrotoxicity- Cisplatin
23. Shake and bake syndrome-Amphotericin B
24. S-Thallidomide-Phocomelia
25. Phenytoin-Gingival hyperplasia
26. Valproic acid-curling of hair
27. Carbamazepine-Aplastic anaemia
28. Anticholinergics-Atropine fever

MICROSCOPY OF SOME IMPOTANT DRUGS
1-Liquorice- Ulignified Septate fibre

2-Solanacoeus Plants- Anisocytic stomata
3-Rhubarb- Star spots
4-Squill- Ca oxide raphides
5-Cardamom- Clothing of glandular trichome
6-Quillaria- Thin membrane arillus
7-Digitalis- Rhytidomes & Glandular Trichomes
8-Atropa Belladona- Anisocytic Stomata
9-Verbascus Thapsus- Clusters of Ca Oxalate
10-Artemisia- T-Shaped Trichomes
11-Stromanium- Phloem Fibres
12-Nuxvomica – Lignified trichomes
13-Fennel- Reticulate lignified trichomes
14-Coriander- Wavy sclerenchyma
15-Indian Dill- Lateral ridges with vascular bundle
16-Anise- Branched & unbranched vittae
17-Cinnamon- Absence of cork & cortex
18-Ginger- Non Lignified vessels & starch grains, Endodermis with no starch
19-Collapsed Endodermis
20-Caraway-Collapsed Parenchyma
21-Chenopodium-Epidermis with no trichomes
22-Chirata- Stomata on lower surface only with no trichomes
23-Cinchona - Large sclerenchymatous bast cells with medullary ray.
24-Cinnamon- Parenchyma cells with starch.
25-Colchicum- Spiral Ducts, Parenchyma with starch
26- Coriander- Prismatic and aggregate crystals of calcium oxalate
27-Saffron- Trichome of stigma
28-Turmeric- Parenchyma with pasty starch
29-Digitalis- Glandular trichomes
30-Euclyptus- Crystal bearing fiber
31-Gentian- Large reticulate ducts
32-Liquorice- Parenchyma with crystals and starch

33-Hycyamus- Endosperm tissue with proteid granules and oil.

34-Ipecac- Parenchyma with raphides
35-Mentha- Trichomes, simple, showing cuticular markings (a medium sized trichome).
36-Pilocarpus- Aggregate crystals of calcium oxalate.
37-Podophyllum- Reticulate ducts and tracheids, Spiral duct,
Aggregate crystals of calcium oxalate, Cork
38-Quassia- Medullary ray with starch, large porous duct
39-Rheum- Parenchyma with starch, resin and crystals, reticulate ducts.
40-Senega- Parenchyma with fat, Cork & Porous duct.
41-Senna- Bast of vascular bundles, Crystal bearing fibers from vascular tissue
42-Stromanium- Parenchyma cells of petiole
43-Strophanthus- Endosperm tissue, showing oil and crystals, Outer tissue with granular
proteid matter and starch
44-Tobbaco- Parenchyma (collenchymatous) from midrib, Leaf parenchyma with chlorophyll.
45-Ginger- Parenchyma with starch and one cell with resin
46-Belladona- Tracheids and spiral duct, Leaf parenchyma cells with crystals, Bast Cells,
Porous ducts & Crystal Sand
DRUG OF CHOISE IMP FOR GPAT

1. Paracetamol poisoning - acetyl cysteine
2. Acute bronchial asthma - salbutamol
3. Acute gout - NSAIDS
4. Acute Hyperkalemia - calcium gluconate
5. Severe DIGITALIS toxicity - DIGIBIND
6. Acute migraine - sumatriptan
7. Cheese reaction - Phentolamine
8. Atropine poisoning - physostigmine
9. Cyanide poisoning - Amyl nitrite
10. Benzodiazepine poisoning - flumazenil
11. Cholera - tetracycline
12. KALA-AZAR - Lipozomal amphotericin- B
13. Iron poisoning - Desferrioxamine
14. MRSA - vancomycin
15. VRSA - LINEZOLID

16. Warfarin Overdose - vitamin-K

17. OCD - fluoxetine
18. Alcohol Poisoning - fomepizole
19. Epilepsy in pregnency - Phenobarbitone
20. Anaphylactic shock - Adrenaline
CANIZZARO REACTION
THE ALDEHIDE DO NO HAVE ALFA HIDROGEN GIVES CANIZARO REACTION IN

PRESENCE OF CONCE. NaOH
2 Molecule of Aldehide + conc. NaOH => ALCOHOL + CARBOXILIC ACID
ONE MOLECULE OF ALDEHIDE GET REDCTION REACTION & PRODUCE

ALCOHOL, OTHER GOT OXIDATION PRODUCE CARBOXILIC ACID

SOME IMPORTANT TOPICS FOR GPAT FROM TABLET AND CAPSULE
 PICKING AND STICKING

This is when the coating removes a piece of the tablet from the core. Overwetting or
examples or excessive film tackiness causes tablets to stick to each other or to the coating
pan. On drying, at the point of contact, a piece of the film may remain adhered to the pan or
to another tablet, giving a “picked” appearance to the tablet surface and resulting in a small
exposed area of the core. It is caused by over-wetting the tablets, by under-drying, or by poor
tablet quality.
REMEDY: A reduction in the liquid application rate or increase in the drying air temperature
and air volume usually solves this problem. Excessive tackiness may be an indication of a
poor formulation.
 TWINNING
This is the term for two tablets that stick together, and it’s a common problem with capsule
shaped tablets.
REMEDY - Assuming you don’t wish to change the tablet shape, you can solve this problem
by balancing the pan speed and spray rate. Try reducing the spray rate or increasing the pan
speed. In some cases, it is necessary to modify the design of the tooling by very slightly
changing the radius. The change is almost impossible to see, but it prevents the twinning
problem.
 COLOR VARIATION
This problem can be caused by processing conditions or the formulation. Improper mixing,
uneven spray pattern and insufficient coating may result in color variation. The migration of
soluble dyes, plasticizers and other additives during drying may give the coating a mottled or
spotted appearance.
REMEDY:
1. The use of lake dyes eliminates dye migration.
2. A reformulation with different plasticizers and additives is the best way to solve film
instabilities caused by the ingredients.

 ORANGE PEEL EFFECT

This refers to a coating texture that resembles the surface of an orange. Inadequate spreading
of the coating solution before drying causes a bumpy or “orange-peel” effect on the coating.
It is usually the result of high atomization pressure in combination with spray rates that are
too high. This also indicates that spreading is impeded by too rapid drying or by high solution
viscosity.
REMEDY: Thinning the solution with additional solvent may correct this problem.
 MOTTLED COLOR
This can happen when the coating solution is improperly prepared, the actual spray rate
differs from the target rate, the tablet cores are cold, or the drying rate is out of specification.
 CAPPING AND LAMINATION

This is when the tablet separates in laminar fashion. Capping is partial or complete separation
of top or bottom crowns of tablet main body. Lamination is separation of a tablet into two or
more distinct layers. Friability test can be used to reveal these problems
The problem stems from improper tablet compression, but it may not reveal itself until you
start coating. How you operate the coating system, however, can exacerbate the problem.
REMEDY: Be careful not to over-dry the tablets in the preheating stage. That can make the
tablets brittle and promote capping.
 ROUGHNESS
A rough or gritty surface is a defect often observed when coating is applied by a spray. Some
of the droplets may dry too rapidly before reaching the tablet bed, resulting in the deposits on
the tablet surface of “spray dried” particles instead of finely divided droplets of coating
solution. Surface roughness also increases with pigment concentration and polymer
concentration in the coating solution.
REMEDY: Moving the nozzle closer to the tablet bed and reducing the degree of
atomization can decrease the roughness due to “spray drying”.

 HAZING / DULL FILM

This is sometimes called Bloom. It can occur when too high a processing temperature is used
for a particular formulation. Dulling is particularly evident when cellulosic polymers are
applied out of aqueous media at high processing temperatures. It can also occur if the coated
tablets are exposed to high humidity conditions and partial salvation of film results.
 BRIDGING
This occurs when the coating fills in the lettering or logo on the tablet and is typically caused
by improper application of the solution, poor design of the tablet embossing, high coating
viscosity, high percentage of solids in the solution, or improper atomization pressure. During
drying, the film may shrink and pull away from the sharp corners of an intagliation or bisect,
resulting in a “bridging” of the surface. This defect can be so severe that the monogram or
bisect is completely obscured.
REMEDY: Increasing the plasticizer content or changing the plasticizer can decrease the
incidence of bridging.
 FILLING
Filling is caused by applying too much solution, resulting in a thick film that fills and
narrows the monogram or bisect. In addition, if the solution is applied too fast, Overwetting
may cause the liquid to quickly fill and be retained in the monogram.
REMEDY: Judicious monitoring of the fluid application rate and thorough mixing of the
tablets in the pan can prevent filling.
 EROSION
This can be the result of soft or friable tablets (and the pan turning too fast), an over-wetted
tablet surface, inadequate drying, or lack of tablet surface strength.
 PEELING AND FROSTING

This is a defect where the coating peels away from the tablet surface in a sheet. Peeling
indicates that the coating solution did not lock into the tablet surface. This could be due to a
defect in the coating solution, over-wetting, or high moisture content in the tablet core which
prevented the coating to adhering.

 CHIPPING
This is the result of high pan speed, a friable tablet core, or a coating solution that lacks a
good plasticizer
 BLISTERING
When coated tablets require further drying in ovens, too rapid evaporation of the solvent from
the core and the effect of high temperature on the strength, elasticity and adhesion of the film
may result in blistering.
REMEDY: Milder drying conditions are warranted in this case.
 CRACKING
It occurs if internal stresses in the film exceed the tensile strength of the film.
REMEDY: tensile strength of the film can be increased by Using higher molecular weight
polymers or polymer blends.
TABLET AND CAPSULE MACHINES
1. Rotosort- for filled/unfilled capsule sorting machine and for de-dusting.
2. Rotofill- to fill pellets in hard gelatin capsule
3. Rotoweigh- A high speed capsule weighing machine.
4. Accogel- filling of dry powder in soft gelatin capsule.
5. Accofill- fill exact powder dose in hard gelatin capsule
6. Wurster- for coating.
7. Osaka- capsule filling machine (powder, granules)
8. Zanasi- capsule filling (powder, pellets, tablets)
9. Lily/parke-davis: capsule filling (powder)
10. Farmatic, holfiger & kary-liquid filling in HGC.
11. Erweka- De-dusting and polishing capsule machine.
12. Seidender- Uses a Belt for visual inspection.
13. Vericap 1200- capsule weighing machine.

PHYTOCHEMICAL SCREENING OF DIFFERENT CLASSES OF

DRUGS IN PHARMACOGNOSY NOTES FOR GPAT
Phytochemical screening is done to identify the nature and type of constituents present in a
drug. This technique is of extreme help when a new drug is being investigated for the chemical
constituents. In phytochemical screening there are both general and specific tests for finding the
nature of chemical constituents in the drug. This topic is very simple and short but contains due
weightage in the GPAT due to its importance in the pharmacognosy. Here I am discussing the
topic in detail stressing on the regions important from the perspective of GPAT.
 GENERAL CHEMICAL TESTS FOR ALKALOIDS:

Alkaloids are tested by the following reagents. Each reagent or test has accuracy and
specificity.
i) Dragendroff’s reagent- This reagent is constituted of Potassium Bismuth Iodide (PBI).
Alkaloids give reddish brown color with the dragendroff’s reagent.
ii) Mayer’s reagent- This reagent is constituted of Potassium Mercuric Iodide (PMI). Alkaloids
give cream color with the Mayer’s reagent. Remember M for Mayer M for Mercuric
iii) Wagner’s reagent- This reagent is constituted of Iodine Potassium Iodide (IPI).
Alkaloids give reddish brown precipitate with the Wagner’s reagent.
iv) Hager’s reagent- This reagent is constitutes of Picric Acid. Alkaloids give yellow
precipitate with the Hager’s reagent.
v) Tannic acid- With tannic acid alkaloids give buff colored precipitate.
vi) Picrolinic acid- Yellow colored precipitate are produced with picrolinic acid.
 CHEMICAL TESTS FOR GLYCOSIDES:

 General test for glycosides- The general test for glycoside is as follows-
Test A- Dissolve the 200 mg drug with sulphuric acid. Then, add 5% NaOH solution for
neutralization. Add Fehling solution A & B to the above mixture. Red color is produced.
Test B- Dissolve the 200 mg drug with sufficient amount of water. Add further water to
dilute the solution. This solution is tested with Fehling solution A & B. Red color is produced
from the reducing sugar present in the drug.
 Compare the red color from the two tests of the drug.
 If the color of test A is more intense than test B; glycoside presence confirmed.

 CHEMICAL TEST FOR ANTHRAQUINONE GLYCOSIDES-
Brontrager’s test- This test is performed for the O-glycosides. Drug is dissolved in 1ml
H2SO4 and mixture is boiled. Filter the solution, filterate is then mixed with chloroform.
Chloroform layer mixed with ammonia gives rose pink color if O-glycosides are present.
Modified brontrager’s test- This test is performed for the investigation of C-glycosides.
Drug is mixed with H2SO4 and FeCl3. The next procedure is same as for the O-glycosides in
brontrager’s test.
Hydroxy anthraquinones- Drug is mixed with Potassium Hydroxide. If hydroxy

anthraquinones are present red color is present.
 CHEMICAL TEST FOR CARDIAC GLYCOSIDES-
Kedde’s test- Extract the drug with CHCl3. 90% alcohol with 2% 3, 5-dinitrobenzoic acid is
added to the extract. To this mixture 20% NaOH is added. Purple color confirms the
presence of cardiac glycoside.
Keller-killiani test- This test is performed only for the digitoxose sugar moiety. Drug is
extracted with chloroform first. 0.4 ml acetic acid is added then along with FeCl3. After
adding H2SO4 if purple color is produced in the acid layer then presence of digitoxose sugar
confirmed.
Raymond’s test- Reagent used in this test is Methanolic alkali. Violet color confirms the
presence of cardiac glycosides.
Legal’s test- This test is performed by using pyridine and alkaline sodium nitroprusside is
used. Red color is produced if cardiac glycoside is present.
Baljet test- Reagent used in this test is picric acid and sodium picrate. Orange color is
produced in the presence of cardiac glycoside.

 CHEMICAL TEST OF CYANOGENETIC GLYCOSIDE-
Sodium picrate test- Drug is mixed with dilute H2SO4. After the addition of sodium picrate
red color is produced in the presence of cyanogenetic glycoside.
Mercuric acetate test- After mixing the mercuric acetate with drug. Drug acetate is formed
and mercury is separated out which confirms the presence of cyanogenetic glycoside.
 CHEMICAL TEST FOR STEROIDS & TERPENOIDS:
i) Liberman-Burchard test- Drug is mixed with acetic anhydride. To this mixture con.
Sulfuric acid is added. There forms two layers with browning at the junction. Upper layer
with green color represents steroids whereas lower layer represents terpenoids red color.
ii) Salwoski test- Drug is mixed with con. Sulfuric acid. Upper layer is of steroids which are
red in color and lower yellow colored layer represents trirepenes.
iii) Sulphur powder test- If sulfur is added to the mixture of drug, sulfur sinks down the
mixture.
 CHEMICAL TEST FOR FLAVONOIDS:
i) Shinoda test- Shinoda test is performed by adding magnesium along with the HCl in the
drug mixture. Red/pink/green to blue color confirms the presence of flavonoids.
ii) Alkaline reagent test- As the name suggests, an alkaline reagent is used for this test.
Sodium hydroxide is added to the drug. Yellow color is produced; if on addition of dilute
acid this color disappears then it confirms the presence of flavonoids.
iii) ZnHCl test- Flavonoids give red color with the Zinc hydrochloride.
 E) CHEMICAL TESTS FOR TANNINS:
i) Gold beater’s skin test- This is most common test for tannins. This test is performed on
the membrane of OX. Goldbeater’s skin is first treated with HCl and rinsed with distilled
water. After this, this skin is paced in the solution of drug and rinsed with water. After
addition of 1% FeSO4, brown or black color is produced in the skin due to the presence of
tannins.

ii) FeCl3 test- Yellow color is produced with FeCl3 in the case of hydrolysable tannins
whereas condensed tannins give green color.
iii) Phenazone test- Sodium phosphate is mixed with drug and filtered. To the filtrate
phenazone is added which produce precipitate if tannins are present.
iv) Gelatin test- Precipitate is produced with gelatin which confirms the presence of tannins.
F) CHEMICAL TESTS FOR VOLATILE OILS:
i) Volatile containing drugs when mixed with alcoholic solution of Sudan III gives red color.
ii) Volatile oil containing crude drugs also produces red color with tincture alkane.
TABLET DOSAGE FORM

Tablet is the most common solid dosage forms prescribed and accepted worldwide. Although
there are various types of tablets available in the market depending upon the size, use and
formulation but the basic excipients used in the formulation of tablet are same everywhere.
 What is tablet?
In simple language, tablet is a solid dosage from comprised of active pharmaceutical
ingredient along with several excipients for attaining the desirable biological and
pharmaceutical properties. From an estimate, two-third of the prescribed medicines in the
world is tablet. Most of the tablets are given through oral route but depending on the need and
patient’s concition it can also be given rectally, vaginally, buccally and sub-lingually.
Size and shape of the tablet also vary according to the formulation and need of the patient.
Some tablets are just of few millimeters while other go up to 1 centimeter. Also, shape of the
tablet can also be either oval, round, capsule shaped etc.
Formulation of the tablet: Different excipients used in the tablet
Beside from the active ingredient, tablet contains various other ingredients like diluents,
binder, disintegrant, glidant and lubricant. Chief role of the excilients in the tablet
formulation is to impart desirable pharmaceutical and biological properties to the tablet. Here
is the detail of the different excipients used in the formulation of the tablet.
 DILUENT
The main role of the diluents in the tablet formulation is to impart bulk to the tablet.
Generally, the active ingredient required in a single tablet ranges from 1 mg to 1000 mg. So,

it is not possible to make a tablet with such small weight therefore diluent is mixed with the
active compound. Major diluents used in the tablet formulation include-
a) CaCO3- Insoluble in water
b) α-Lactose- Most common, inexpensive and inert
c) Mannitol- Used for chewable tablets
d) Microcrystalline cellulose- Increase disintegrant property also
 DISINTEGRANTS
Disintegrants are used for the purpose of breaking the tablet when introduced in the
biological system. Mainly water and pH of the system are responsible for the disintegration
of the tablet. Tablet after disintegration releases its active constituent into the system which
exerts its pharmacological action. Disintegrants used in the tablet are-
a) Alginic acid/Na Alginate – Used concentration is 2-10% w/v
b) Na carboxy methyl cellulose (Nymcel) - Used concentration is 1-20% w/v
c) Microcrystalline cellulose (Avicel) - Used concentration is 10% w/v
d) Starch - Used concentration is 2-10% w/v
 BINDERS (GRANULATING AGENT)

Binders are used to increase the cohesive forces between the ingredients of the tablet so that
tablet can be compressed easily. The concentration of the binder should be used carefully as it
can greatly influence the properties of the tablet. Binders used in the tablet formulation are:
a) Acacia mucilage (20%) - It gives very hard granules.
b) Gelatin (5-20%)
c) PVP (2-10%) – Used for Non-aqueous granulation
d) Starch (5-10%) - Common binder
e) Tragacanth (20%) – Gives hard granules
 GLIDANTS/FILLER
Glidants are used to enhance the flow properties of the granules or powders so that granules
do not stick with each other. Mainly at present there are only two types of glidants used in the
tablet formulation:
a) Colloidal Silica (0.1-0.5%) – Most common and excellent glidant properties
b) Talc (1-2%)

 LUBRICANTS
Lubricants are used for the comfortable ejection of the tablet from punching machine without
sticking to the die walls. Lubricants used in the tablet formulation include-
a) Stearic acid
b) Liquid Paraffin (5%)
c) Na Benzoate (5%)
d) Na Lauryl sulphate (0.5-5%)
(For tablet and capsule chapter LACHMAN is the best book for GPAT so also refer the
LACHMAN once along with this study material)

MICROBIOLOGY
 Control of microorganisms
Reduction in numbers and / or activity of the total Achieved by
• Physical agents
• Chemical agents
• Chemotherapeutic agents
 Antimicrobial action is influenced by some factors:

• Environment: Effectiveness of heat is greater in presence of water, acid than in alkali,
consistency of the material (aqueous or viscous), and presence of organic matter.
• Kinds of microorganisms: Growing vegetative cells more susceptible than spore forms,
bacterial spores most resistant of all living organisms.
• Physiological state of cells: Young actively metabolizing cells more susceptible than old,
dormant cells.
 Mode of action of antimicrobial agents:

• Damage to the cell wall or inhibition of cell wall synthesis
• Alteration of the permeability of the cytoplasmic membrane
• Alteration of the physical or chemical state of proteins and nucleic acids
• Inhibition of enzyme action
• Inhibition of protein or nucleic acid synthesis
 Control by Physical agents:

• High temperature
• Low temperature
• Desication : Time of survival of microorganisms after desiccation depends upon factors –
kind of microorganisms, material on which the organisms are dried, completeness of drying
process, physical conditions to which the dried organisms are exposed – light, temperature,
humidity..
• Osmotic pressure
• Radiations – Ionising radiations: knock out electrons from molecules and ionize them
forming hydrogen radicals, hydroxyl radicals, peroxides.
• Non-ionising radiations: less energetic, absorbed specifically by different compounds
causing excitation of their electrons and raise them to higher energy levels.

• UV radiations are absorbed most specifically by nucleic acids – pyrimidine dimers thus
inhibiting DNA replication and resulting mutations.
• Filters – HEPA (high efficiency particulate air) filters.
Control by Chemical agents

General terms for use with various chemical agents of control:
• Sterilization: is a process in which all viable life forms are either killed or removed.
• Disinfectant: kills growing forms not necessarily the spores of disease producing organisms
• Disinfection: Process of killing infectious agents
• Antiseptic: that opposes sepsis. Usually associated with substances applied to the body
• Sanitizer: that reduces the microbial population to safe levels. Applied to equipment and
utensils used in food industries, restaurants etc.
• Germicide (microbicide): that kills vegetative forms but not necessarily the spores of
germs/microorganisms.
• Bactericide: that kills bacteria
• Bacteriostatic: A condition in which the growth of bacteria is prevented.
• Chemotherapeutic agents: used to treat infections.
Major groups of chemical antimicrobial agents:

Phenols and phenolic compounds:
Phenol was the first disinfectant used in 1880 by Joseph Lister to reduce the infection of
surgical incisions. Used as a standard against which other disinfectants are compared to
determine their antimicrobial activity. Cresol, phenyl phenol etc. are very effective
disinfectants. A 5% solution of phenol rapidly kills the vegetative cells of microorganisms.
• Mode of action:
Precipitation of proteins, inactivation of enzymes, leakage of amino acids from cells.
Phenol coefficient technique: Test organisms are Salmonella typhi or Staphylococcus
aureus. It is calculated by dividing the greatest dilution of the disinfectant killing the test
organism in 10 min but not in 5 min with the greatest dilution of the phenol showing the same
result.
Alcohols: Ethyl alcohol in concentrations between 50 and 90% is effective against
vegetative or non-spore forming cells. Methyl alcohol is less bactericidal, higher alcohols –
propyl, butyl, amyl are more germicidal than ethyl alcohol but since the alcohols higher than
propyl are not miscible with water, they are not commonly used in disinfectants.

• Mode of action: Protein denaturants, also damage the lipid complex in cell membrane.
Halogens:
Iodine is one of the oldest and most effective germicidal agents.
Tincture of iodine. Also used in the form of substances – iodophores –
Mixtures of iodine with surface-active agents – polyvinylpyrrolidone (PVP).
• Mode of action: Oxidises and inactivates essential metabolic compounds – Proteins with
sulfhydryl groups.
• Chlorine and chlorine compounds: Chlorine gas, hypochlorites, chloramines.
• Mode of action: when chlorine is added in water it forms hypochlorous acid which is
further decomposed to form nascent oxygen. Nascent oxygen being a strong oxidizing agent
denatures major cellular constituents. Chlorine can also combine directly with proteins of cell
membranes and enzymes.
Cl2 + H2O = HCl + HClO (hypochlorous acid)
HClO = HCl + O
 Heavy metals and their compounds:
Mercury, silver, copper. By combining with cellular proteins especially containing sulfhydryl
groups and inactivating them.
 Dyes:
• Triphenylmethane dyes - malachite green, brilliant green, crystal violet.
Gram +ve bacteria more susceptible than gram –ve. Interfere with cellular oxidation
processes.
• Acridine dyes – acriflavine, tryptoflavine. Selective inhibition against staphylococci and
gonococci.
Synthetic detergents:
Detergents are wetting agents, surface tension depressants.
• Anionic detergents – those with detergent property resident in the anion
Soap, Sodium lauryl sulphate (SLS).
• Cationic detergents – those with detergent property resident in cation
Cetylpyridinium chloride. Cationic detergents are more germicidal than anionic compounds.
• Quaternary ammonium compounds: Most of germicidal cationic-detergent
 Compounds are quaternary ammonium salts in which R1, R2, R3 and R4 groups are
 Carbon groups linked to the nitrogen atom.
 The bactericidal power is high againt Gram+ve bacteria.
Mode of action: denaturation of proteins, interference with glycolysis and Membrane damage.

Aldehydes:
Most effective are formaldehyde and gluteraldehyde. Highly reactive chemicals – combine
readily with vital nitrogen compounds – proteins, nucleic acids.
Gaseous agents:
Ethylene oxide – powerful sterilizing agent – liquid at <10.8oC – highly flammable.
• Mode of action – Alkylation reactions with organic compounds – enzymes and proteins.
Antibiotics and other chemotherapeutic agents:

• Inhibition of cell wall synthesis
• Damage to cytoplasmic membrane
• Inhibition of nucleic acid and protein synthesis
• Inhibition of specific enzyme systems
• Inhibition of cell wall synthesis: Penicillins, ampicillin, cephalosporins – interfere with

final stages of Peptidoglycan synthesis – inhibit transpeptidase reaction – cross-linking of the
two linear polymers.
Cycloserine, vancomycin - inhibits the enzymes involved in the synthesis of pentapeptide side chains.
• Damage to cytoplasmic membrane: Polymyxins, Gramicidins, Tyrocidines – act on
membrane having sterols – fungi and animal cells but not bacteria.
• Inhibition of nucleic acid and protein synthesis: Streptomycin, tetracycline – interfere
with binding of 30S ribosomes, chloramphenicol, erythromycin - binds with 50s ribosome.
• Inhibition of specific enzyme systems – Sulfonamides
Antifungal antibiotics – Nystatin, Griseofulvin
Synthetic chemotherapeutic agents: Nitrofurans – both g+ve and g-ve bacteria,
Nalidixic acid – Inhibition of DNA synthesis in g-ve bacteria.
 CONTROL OF MICROORGANISMS IN FOODS
Aseptic handling
High Temperature – Boiling, Steam under pressure, Pasteurization, Sterilization,
Aseptic processing
Low Temperature – Refrigeration, Freezing,
Dehydration
Osmotic pressure – In concentrated sugar, brine

Chemicals – Organic acids, SO2, substances developing during food processing, substances
contributed by microbial activity (acids)
Radiations – Ionizing radiations, non-ionizing radiations
High Temperature: One of the safest and most reliable methods. Steam under pressure
cooker, most effective as it destroys all vegetative cells and spores.
Canning – 100oC for high acid foods, 121oC for low acid foods.
Pasteurization: LTH T– 145oF (62.8oC) for 30 min, HTST – 161oF (71.7oC) for 15 sec.
This destroys all yeasts, Molds, gm-ve bacteria and most gram+ve bacteria.
Most heat resistant pathogen Coxiella Burnetti is also killed.
Sterilization: UHT -140-150oC for few seconds.
To understand thermal destruction of microorganisms for use in Food Preservation it is
necessary to understand certain basic concepts:
Thermal Death Time (TDT): Time necessary to destroy a given population of
microorganisms at a specified time.
Thermal Death Point (TDP): Temperature necessary to destroy a given population of
microorganisms in a fixed time, usually 10 min.
Decimal reduction Time (D Value): Time necessary to destroy 90% of the organisms at a
particular temperature.
Z Value: Temperature in oF required to vary D value by 90%.
D Value: Indicates resistance of microorganisms of to a specified temperature.
Z Value Indicates relative resistance to different temperatures.
Z value is used to construct equivalent thermal processes.
At 220oF, D value = 113 min
At 203.5oF, D value = 1130 min (If Z value is 17.5 oF)
At 237.5oF, D value = 11.3 min (If Z value is 17.5 oF)
Aseptic Packaging: In traditional canning methods non-sterile food is placed in a non-sterile

metal/glass container followed by container closure and sterilization.
In aseptic packaging sterile food is placed in a sterile container under aseptic conditions and
sealed under aseptic conditions.

Low temperature: Activities of spoilage organisms are lowered or stopped.
Dehydration: Drying reduces the aw and thus prevents the growth of microorganisms.
Osmotic pressure: NaCl and sugars exert drying effect – Plasmolysis – death.
Halodurics, halophiles, Osmophiles tolerate the high osmotic pressure.
Direct antimicrobials:
Benzoic acid and parabens:
C6H5COOH and its sodium salt –
C7H5NaO2 along with esters of p-Hydroxybenzoic acid (Parabens).
Antimicrobial activity of benzoate is affected by pH – Greatest activity at low pH –
Ineffective at neutral pH.
ANTIMICROBIAL ACTIVITY RESIDES IN UN-DISSOCIATED MOLECULE

 At pH 4.0 60% compound is un-dissociated.
 At pH 6.0 only 1.5% compound is un-dissociated.
Effective against yeasts and molds.
Generally employed in high acid foods – Apple juice, Soft drinks, Tomato ketchup and
Salads.
Max permissible limit is 0.1%
Common permissible parabens are heptyl-. Methyl-, propyl-, butyl-, ethyl-,
Parabens less sensitive to pH than benzoate – effective upto pH 8.0
Both benzoate, and parabens block oxidation of glucose to pyruvic acid.
Also inhibit uptake of substrate molecules.
SORBIC ACID:
CH3CH=CHCH+CHCOOH – usually employed as Ca, Na or K salt. Permissible limit is
0.2%
Like benzoate also active in acid foods than neutral foods
Generally in-effective at pH >6.5.
 At pH 4.0, 86% un-dissociated
 At pH 6.0, 6% compound is un-dissociated

Generally effective against molds and yeasts but also to certain bacteria.
Generally used in bakery products, cheese, fruit juices, beverages, salad dressings.
Inhibits dehydrogenase enzyme system.
Also inhibition of cellular uptake of substrate molecules – amino acids, phosphate, organic acids.
PROPIONIC ACID:
CH3CH2COOH as Ca and Na salts.
Mainly a mold inhibitor – used in breads, cakes, cheese.
At pH 4.0 88% is un-dissociated
At pH 6.0 6.7% is un-dissociated
Inhibits cellular uptake of substrate molecules
SULPHUR DIOXIDE AND SULPHITES:

SO2, Na or K salts of SO3 (sulphite), HSO3 (Bisulphite), S2O5 (metabisulphite).
Generally effective againt bacteria
Aerobes more sensitive than anaerobes
More active at acidic pH
SO2 < pH 3.0. HSO3 at pH 3.0-5.0, SO3 > pH 6.0.
At higher concentration yeasts and molds are also inhibited.
Permissible limit is 100-200 ppm
Effect is due to reducing power – reduces the O2 tension to a point at which aerobes are not
able to grow. Also act on enzyme systems – enzyme poison – generally act on disulphide
bonds.
Also used in dried foods to prevent enzymatic browning.
NITRITES AND NITRATES:

Many bacteria are capable of utilizing nitrate as electron acceptor which is reduced to nitrite
highly reactive and capable of serving both reducing and oxidizing agent.
Under acidic conditions it ionizes to form nitrous acid (HONO) – further decomposes to give
nitric oxide (NO) – capable of reacting with catalase, peroxidases, and cytochromes thus
inhibiting aerobic bacteria.

1. What is Regulatory Affairs?

Ans-Regulatory Affairs in a Pharmaceutical industry, is a profession which acts as the
interface between the pharmaceutical industry and Drug Regulatory authorities across the
world. It is mainly involved in the registration of the drug products in respective countries
prior to their marketing.
2. What are the goals of Regulatory Affairs Professionals?

Ans- Protection of human health Ensuring safety, efficacy and quality of drugs Ensuring
appropriateness and accuracy of product information
3. What are the Roles of Regulatory Affairs professionals?

Ans- Act as a liaison with regulatory agencies Preparation of organized and scientifically
valid NDA, ANDA,INDA ,MAA,DMF submissions Ensure adherence and compliance with
all the applicable cGMP, ICH, GCP, GLP guidelines, regulations and laws Providing
expertise and regulatory intelligence in translating regulatory requirements into practical
workable plans Advising the companies on regulatory aspects and climate that would affect
their proposed activities Apart from the above main roles, there are various other roles which
Regulatory Affairs professionals play.
4. What is an Investigational New Drug (IND) application?

Ans- It is an application which is filed with FDA to get approval for legally testing an
experimental drug on human subjects in the USA
5. What is a New Drug Application?

Ans- the NDA is the vehicle through which drug sponsors formally propose that the FDA
approve a new pharmaceutical for sale and marketing in the U.S. The data gathered during
the animal studies and human clinical trials of an Investigational new drug become part of the
NDA In simple words, “It is an application which is filed with FDA to market a new
Pharmaceutical for sale in USA”
6. What is an Abbreviated New Drug Application (ANDA)?

Ans- It is an application filed with FDA, for a U.S. generic drug approval for an existing
licensed medication or approved drug. In simple words, “It is an application for the approval
of Generic Drugs “

7. What is a Generic Drug Product?

Ans- A generic drug product is the one that is comparable to an innovator drug product in
dosage form, strength, route of administration, quality, performance characteristics and
intended use.
8. What is a DMF?
Ans- A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA)
that may be used to provide confidential detailed information about facilities, processes, or
articles used in the manufacturing, processing, packaging, and storing of one or more human
drugs.Important facts regarding DMFs It is submitted to FDA to provide confidential
informationIts submission is not required by law or regulationsIt is neither approved nor
disapprovedIt is filed with FDA to support NDA, IND, ANDA another DMF or amendments
and supplements to any of theseIt is provided for in the 21 CFR (Code of Federal
Regulations) 314. 420It is not required when applicant references its own information
9. What are the types of DMF’s?

Ans-Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel (No longer
accepted by FDA) Type II: Drug Substance, Drug Substance Intermediate, and Material Used
in Their Preparation, or Drug Product Type III: Packaging Material Type IV: Excipient,
Colorant, Flavour, Essence, or Material Used in Their Preparation Type V: FDA Accepted
Reference Information (FDA discourages its use)
10. What is a 505 (b) (2) application?

Ans- 505 (b)(2) application is a type of NDA for which one or more investigations relied on
by applicant for approval were not conducted by/for applicant and for which applicant has not
obtained a right of reference.
11. What kind of application can be submitted as a 505(b) (2) application?

Ans- New chemical entity (NCE)/new molecular entity (NME) Changes to previously
approved drugs
12. What are the examples of changes to approved drug products for which 505(b) (2)
application should be submitted?
 Ans- Change in dosage form.

 Change in strength
 Change in route of administration Substitution of an active ingredient in a formulation
product
 Change in formulation
 Change in dosing regimen
 Change in active ingredient new combination Product
 New indication
 Change from prescription indication to OTC indication
 Naturally derived or recombinant active ingredient
 Bioequivalence
13. What are the chemical classification codes for NDA?

 Number Meaning
 New molecular entity (NME)
 New ester, new salt, or other monovalent derivative
 New formulation
 New combination
 New manufacturer
 New indication
 Drug already marketed, but without an approved NDA
 OTC (over-the-counter) switch
14. What are the differences between NDA and 505 (b) (2) application?
Ans- S.No.New Drug Application (NDA) 505 (b) (2) Application
 All investigations relied on by applicant for approval were conducted by/for applicant
and for which applicant has right of reference One or more investigation relied on by
applicant for approval were not conducted by/for applicant and for which applicant
has not obtained a right of reference
 Generally, filed for newly invented pharmaceuticals. Generally, filed for new dosage
form, new route of administration, new indication etc for all already approved
pharmaceutical. Note: 505 (b) (2) application is a type of NDA.

15. What is a Marketing Authorization Application?

Ans- It is an application filed with the relevant authority in the Europe (typically, the UK's
MHRA or the EMA’s Committee for Medicinal Products for Human Use (CHMP)) to market
a drug or medicine. As per UK’s MHRA-Applications for new active substances are
described as 'full applications’. Applications for medicines containing existing active
substances are described as 'abbreviated’ or ‘abridged applications’.
16. What is an ASMF?

Ans-Active substance master file is a submission which is made to EMA, MHRA or any
other Drug Regulatory Authority in Europe to provide confidential intellectual property or
'know-how' of the manufacturer of the active substance. In simple words, “It is a submission
made to European Drug regulatory agencies on the confidential information of Active
Substance or Active pharmaceutical Ingredient (API)”.
17. What are the types of active substances for which ASMFs are submitted?
Ans-New active substances existing active substances not included in the European
Pharmacopoeia (Ph. Eur.) or the pharmacopoeia of an EU Member StatePharmacopeial active
substances included in the Ph. Eur. or in the pharmacopoeia of an EU Member State
18. What is the difference between DMF and ASMF (with respect to submission)?
Ans-ASMF is submitted as Applicant’s Part (Open Part) and Restricted Part (Closed Part)
there isn’t any differentiation of DMF’s into parts
19. What is ICH?

Ans-International Conference on Harmonisation of Technical Requirements for Registration
of Pharmaceuticals for Human Use (ICH): is a project that brings together the regulatory
authorities of Europe, Japan and the United States and experts from the pharmaceutical
industry in the three regions to discuss scientific and technical aspects of pharmaceutical
product registration.
20. What is CTD?

Ans-The Common Technical Document (CTD) is a set of specification for application
dossier, for the registration of Medicines and designed to be used across Europe, Japan and
the United States. Quality, Safety and Efficacy information is assembled in a common format

through CTD .The CTD is maintained by the International Conference on Harmonisation of

Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).CTD
format for submission of drug registration applications/dossiers is widely accepted by
regulatory authorities of other countries too like Canada, Australia etc.
21. What are the ICH guidelines to be referred for preparation of registration
dossiers/applications of medicines (With respect to format and contents in each
module)?
 M4 Guideline
 M4Q Guideline
 M4S Guideline
 M4E Guideline
22. What are the modules in CTD?

Ans- the Common Technical Document is divided into five modules:
 Module 1. Administrative information and prescribing information
 Module 2. Common Technical Document summaries
(Overview and summary of modules 3 to 5)
 Module 3. Quality
 Module 4. Nonclinical Study Reports (toxicology studies)
 Module 5. Clinical Study Reports (clinical studies)
22. What is Orange Book?

Ans-It is the commonly used name for the book “Approved Drug Products Equivalence
Evaluations”, which is published by USFDA.It contains the list of drug products, approved
on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under
the Federal Food, Drug, and Cosmetic Act.
23. What is Hatch-Waxman act?

Ans-It is the popular name for Drug Price Competition and Patent Term Restoration Act,
1984. It is considered as the landmark legislation which established the modern system of
generic drugs in USA. Hatch-Waxman amendment of the federal food, drug and cosmetics
act established the process by which, would be marketers of generic drugs can file

Abbreviated New Drug Application (ANDA) to seek FDA approval of generic drugs.
Paragraph IV of the act, allows 180 day exclusivity to companies that are the "first-to-file" an
ANDA against holders of patents for branded counterparts.In simple words “Hatch-Waxman
act is the amendment to Federal, Food, Drug and Cosmetics act which established the modern
system of approval of generics ”
24. What are the patent certifications under Hatch-Waxman act?

Ans-As per the Hatch and Waxman act, generic drug and 505 (b) (2) applicants should
include certifications in their applications for each patent listed in the “Orange Book” for the
innovator drug. This certification must state one of the following:(I) that the required patent
information relating to such patent has not been filed (Para I certification);(II) that such
patent has expired (Para II certification);(III) that the patent will expire on a particular date
(Para III certification); or(IV) that such patent is invalid or will not be infringed by the drug,
for which approval is being sought(Para IV certification).A certification under paragraph I or
II permits the ANDA to be approved immediately, if it is otherwise eligible. A certification
under paragraph III indicates that the ANDA may be approved when the patent expires.
25. What is meant by 180 day exclusivity?

Ans-The Hatch-Waxman Amendments provide an incentive of 180 days of market
exclusivity to the “first” generic applicant who challenges a listed patent by filing a paragraph
IV certification and thereby runs the risk of having to defend a patent infringement suit.180
Day Exclusivity could be granted to more than one applicant.
The recent example is- 180 day exclusivity was granted to Ranbaxy and Watson Laboratories
for marketing generic version of Lipitor (Atorvastatin calcium).
26. What are the procedures for Approval of Drug in EU?

 Centralised Procedure (CP)
 Decentralised Procedure (DCP)
 Mutual Recognition Procedure (MRP)
 National Procedure (NP)

27. What is the Full form of abbreviation, CEP?

Certificate of Suitability to the monographs of the European Pharmacopoeia (or) Certificate
of suitability of monographs of the European Pharmacopoeia (or) Certification of suitability
of European Pharmacopoeia monographs
It is also informally referred to as Certificate of Suitability (COS)
28. What is a CEP?

Ans. It is the certificate which is issued by Certification of Substances Division of European
Directorate for the Quality of Medicines (EDQM), when the manufacturer of a substance
provides proof that the quality of the substance is suitably controlled by the relevant
monographs of the European Pharmacopoeia.
29. What are the recently approved new Drugs by FDA (Under NDA Chemical Type 1)?
AS. NO. NDA NAME OF DRUG NAME OF ACTIVE INGREDIENT COMPANY
1203188 KALYDECOIVACAFT OR VERTEX PHARMS
2203388 ERIVEDGE VISMODEGIBGENEN TECH
3202324 INLYTA AXITINIBPFIZER
4202833 PICATOINGENOL MEBUTATELEO PHARMA AS
5202514 ZIOPTAN TAFLUPROSTMERCK SHARP DOHME
6021746 SURFAXINLUCINACTANT DISCOVERY LABORATORIES INC30.
FULL FORM
NDA New Drug Application
ANDA Abbreviated New Drug application
IND Investigational New Drug Application
DMF Drug Master File
ASMF Active Substance Master File
MAA Marketing Authorisation Application
Certificate of Suitability to the monographs of the European

CEP
Pharmacopoeia

The International Conference on Harmonisation of technical

ICH
requirements for registration of Pharmaceuticals for human use.
Common technical document for the registration of pharmaceuticals

CTD
for human use.
AP Applicant’s Part
RP Restricted Part
OP Open Part
CP Closed Part
NME New Molecular Entity
NCE New Chemical Entity
SmPC Summary of Product Characteristics
PL Packaging Leaflet
RMS Reference Member State
CMS Concerned Member State
CHMP The Committee for Medicinal Products for Human Use
CPMP Committee for Proprietary Medicinal Products
CVMP Committee for Medicinal Products for Veterinary Use
SUPAC Scale-up and post approval changes
BACPAC Bulk Active Chemicals Post approval Changes
cGMP Current good Manufacturing Practice
GCP Good clinical Practice
GLP Good Laboratory Practice
31. Well known Drug Regulatory Agencies across the world-

NAME OF COUNTRY REGULATORY AGENCIES
United States of America United States Food and Drug Administration (USFDA)
Medicines and Healthcare products Regulatory Agency
United Kingdom
(MHRA)

European Union European Medicines Agency (EMA)
European Union European Directorate for the Quality of Medicines (EDQM)
Australia Therapeutic Goods Administration (TGA)
Therapeutic Products Directorate (TPD) in Health Product

Canada
and food branch (HPFB) of Health Canada (HC)
Japan Pharmaceutical and Medical Devices Agency (PMDA)
Agence Francaise de Securite Sanitaire des Produits de Sante

France (AFSSAPS)Translated into English as- French Agency for the
Safety of Health Products
Bundesinstitut für Arzneimittel und Medizinprodukte,

Germany (BfArM) Tanslated into English as- Federal Institute for
Drugs and Medical Devices
Agência Nacional de Vigilância Sanitária (ANVISA)
Brazil Tanslated into English as- The National Health Surveillance
Agency
Drugs Controller General of India (DCGI) who heads Central

India
Drugs Standard Control Organisation (CDSCO)
Switzerland Swiss Agency for Therapeutic Products (SWISSMEDIC)
Singapore Health Sciences Authority (HSA)

D & C ACT (1940) LIST OF AMENDING ACTS AND ADAPTATION ORDER

1. The Repealing and Amending Act, 1949 (40 of 1949).
2. The Adaptation of Laws Order, 1950.
3. The Part B States (Laws) Act, 1951 (3 of 1951)
4. The Drugs (Amendment) Act, 1955 (11 of 1955)
7. The Drugs and Cosmetics (Amendment) Act, 1964 (13 of 1964)
8. The Drugs and Cosmetics (Amendment) Act, 1972 (19 of 1972).
THE DRUGS AND COSMETICS ACT, 1940

ARRANGEMENT OF SECTIONS
CHAPTER I
INTRODUCTORY
SECTIONS
1. Short title, extent and commencement.

2. Application of other laws not barred.
3. Definitions
3A. Construction of references to any law not in force or any functionary not in existence in
the State of Jammu and Kashmir.
4. Presumption as to poisonous substances.
CHAPTER II
THE DRUGS TECHNICAL ADVISORY BOARD, THE CENTRAL DRUGS
LABORTORY AND THE DRUGS CONSULTATIVE COMMITTEE
5. The Drugs Technical Advisory Board.

6. The Central Drugs Laboratory.
7. The Drugs Consultative Committee.
7A. Section 5 and 7 not to apply Ayurvedic, Siddha or Unani drugs.

CHAPTER III
IMPORT OF DRUGS AND COSMETICS
8. Standards of quality
9. Misbranded drugs
9A. Adulterated drugs
9B. Spurious drugs.
9C. Misbranded cosmetics.
9D. Spurious cosmetics
10 Prohibition of import of certain drugs or cosmetics.
10A. Power of Central Government to prohibit import of drugs and cosmetics in public interest.
11. Application of law relating to sea customs and powers of Customs officers.
12 Power of Central Government to make rules.
13 Offences.
14 Confiscation
15. Jurisdiction
CHAPTER IV
MANUFACTURE, SALE AND DISTRIBUTION OF DRUGS AND COSMETICS
SECTIONS
16. Standards of quality.
17. Misbranded drugs.
17A. Adulterated drugs.
17B. Spurious drugs.
17C. Misbranded cosmetics.
17D. Spurious cosmetics.
18. Prohibition of manufacture and sale of certain drugs and cosmetics.
18A. Disclosure of the name of the manufacturer, etc.
18B. Maintenance of records and furnishing of information.
19. Pleas .
20. Government Analysts.
21. Inspectors.
22. Powers of Inspectors.
23. Procedure of Inspectors.
24. Persons bound to disclose place where drugs or cosmetics are manufactured or kept.

25. Reports of Government Analysts.

26. Purchaser of drug or cosmetic enabled to obtain test or analysis.
26A. Power of Central Government to prohibit manufacture etc. of drug and cosmetic in
public interest.
27. Penalty for manufacture, sale, etc., of drugs in contravention of this Chapter.
27A. Penalty for manufacture, sale, etc., of cosmetics in contravention of this Chapter.
28. Penalty for non-disclosure of the name of the manufacturer, etc.
28A. Penalty for not keeping documents, etc., and for non-disclosure of information.
28B Penalty for manufacture, etc. of drugs or cosmetics in contravention of section 26A.
29. Penalty for use of Government Analyst’s report for advertising.
30. Penalty for subsequent offences.
31. Confiscation.
31A. Application of provisions to Government departments.
32. Cognizance of offences.
32A. Power of Court to implead the manufacturer, etc.
33. Power of Central Government to make rules .
33A. Chapter not to apply to Ayurvedic, Siddha or Unani drugs.
CHAPTER IVA
PROVISIONS RELATING TO AYURVEDIC SIDDHA AND UNANI DRUGS
SECTIONS
33B. Application of Chapter IVA.
33C. Ayurvedic, Siddha and Unani Drugs Technical Advisory Board.
33D. The Ayurvedic, Siddha and Unani Drugs Consultative Committee.
33E. Misbranded drugs.
33EE. Adulterated drugs.
33EEA. Spurious drugs.
33EEB. Regulation of manufacture for sale of Ayurvedic, Siddha and Unani drugs.
33EEC. Prohibition of manufacture and sale of certain Ayurvedic, Siddha and Unani drugs.
33EED. Power of Central Government to prohibit manufacture etc., of
Ayurvedic, Siddha or Unani drugs in public interest.
33F. Government Analysts.
33G. Inspectors .
33H. Application of provisions of sections 22, 23, 24 and 25.

33I. Penalty for manufacture, sale, etc., of Ayurvedic, Siddha or Unani drugs in
contravention of this Chapter.
33J. Penalty for subsequent offences.
33K. Confiscation.
33L. Application of provisions to Government departments.
33M. Cognizance of offences.
33N. Power of Central Government to make rules.
33O. Power to amend First Schedule.
CHAPTER V MISCELLANEOUS
33P. Power to give directions.
34. Offences by companies.
34A. Offences by Government departments.
34AA. Penalty vexatious search or seizure.
35. Publication of sentences passed under this Act.
36. Magistrate’s power to impose enhanced penalties.
36A. Certain offences to be tried summarily.
37. Protection of action taken in good faith.
38. Rules to be laid before Parliament.
YEAR AND ACT
1970 Indian Patents Act

1919 Poison Act
1948 Pharmacy Act
1940 Drug and Cosmetic Act
1930 Dangerous Drug Act
1857 Opium Act
1954 Drug and Magic Remedies Act
1971 Medical Termination of Pregnancy Act (MTP)
1989 First ICH Indian pharmacopoeias:
1955 1st Edition IP
1966 2nd Edition IP

1985 3rd Edition IP

1996 4th Edition IP
2007 5th Edition IP
2010 6th Edition IP
2014 7th Edition IP
TECHNIQUE FOR NANOPARTICLE PREPARATION:

 Desolvation, denaturation
 Emulsion & interfecial polymerization
 Emulsification diiffusion
 Salting out.
STRENGTHS
 HCl (IP)-36
 H2SO4-12 N
IMP CHARACTERS:
 Nutmeg-Aril
 Stropanthus- Arista (Awn)
 Cardamon- Arilode
 Colchicum- Strophiole
 Castor- Caruncle
WHITEFIELD OINTMENT
 6%benzoic acid
 3%salicylic acid.
 Used as keratolytic.
SMART POLYMER:
 Polylactic acid
 Polyglycolic acid
 Poly-lactide co-glycolide
 Poly (dl-lactide-co-caprolactone)
 N-isopropylacrylamide
Difference between Aldol condensation & Cannizaro reaction:
 If aldehyde & ketone have alpha proton than Aldol condensation occur.
 If not, than cannizaro reaction occurs.

 SOME IMPORTANT NOTES FOR GPAT EXAM

 Betonite - derivative of monmorillonite.
 Hydrocaprolic acid-cyclic unsat fatty acid.
 Glucose-No UV abs.
 Vitamin B6 deficiency- sideroblastic anemia
 Smell of acetophenone when lobelia leaves burn.
 Rauwolfia tetraphylla devoid of recinnamine.
 Bromhexin- semisynthetic from vasaka.
 All electron withdrawing functional group are generally Meta directing except halogen group
 Stability order of carbocation is 3>2>1...
 Herceptin is Antineoplastic agent which cause CHF.
 Rasagaline is free from amphetamine prop due 2 aminoindane metabolite
 Rheumatoid factor is usually Ig M.
 Ca. sandoz is product of NOVARTIS.
 Phosphate is salt of Codeine.
 Seed of Indrajav is kurchi
 Transferosome are liposome used to increase Transdermal Permeation, in this
deformability achieved by using surfactant in proper ratio.
 Abacavir, a nucleoside reverse transcriptse inhibitor NRTI is converted to which
active metabolite?? Ans is Carbovir triphosphate.
 Cholesterol used in liposomes because it fills gaps created by imperfect packing of
lipids when protein are embeded in membrane.
 Clenbutrol - anabolic drug uesd illicitly by athletes 2 improve performance
 For chest infection in asthma-clarithromycin used.
 Lotaustralin- isoleucin
 Squill, Manna, Psyllium Contain Trisaccharide.
 Diluents can be used in ratio 5-10% in tablet.
 In MRI max of 1.5 tesla magnetic field strength can be used.
 Lutrol is known as intelligent polymer.
 Chemical shift-independent of magnetic field
 Secondary structure of protein-alfa-beta helix
 1960-prevention of cruelty to animals act.
 1963-CPCSEA came into existence.
 1998-breeding of and experimentation on animals act.

 Hydrolysis of ethyl acetate is pseudo first order reaction

 Suspensions follow pseudo zero order reaction
 Cis form gives 5-12 delta value and trans form gives 12-18 delta value in NMR
 Polystyrene and water are both used as standard for calibration of IR
 B-cyclodextrin has max Solubility
 H-bond can detected by IR & NMR
 Free radicals are identified by E.S.R (electron spin resonance)
 TRIPS-trade related aspects of intellectual property rights
 TRIMS-trade related investment measures
 WIPO-world intellectual property organisation.
 Seliwanoffs reagent contain resorcinol + glacial acetic acid.
 Lucas reagent HCl+ZnCl2.
 Ames test to detect carcinogenicity
 Nitrocellulose is used as base in nail lacquers.
 Nucleosome contain DNA with histone protein in ratio 30:1
 Neumanns test is used for the identification of Casein.
 Gaultheria con. Methyl salicylate.
 PULSED FLOW IS THE disadvantage of reciprocating pump in HPLC.
 P.bracteatum do not contain morphine.
 BENTING & BEST founded insulin.
 H1N1-'N' stands for Neuramidase.
 Fiehls test is used for determination of sucrose
 Shinoda test for identification of flavanoids.
 Murexide test for caffeine.
 Bacteria need 0.5%NaCl for maintaining isotonicity not 0.9% NaCl.
 RITONAVIR IS also known as pharmacokinetic enhancer. Because it increases
bioavailability of antiviral drugs.
 Banana bond is the characteristic of cyclopropane.
 Caffine is Pseudo tannin.
 Rivastigmine is used in Alzheimer’s disease and it is a pseudo irreversible inhibitor of
cholinesterase enzyme.
 Carvedilol-a mixed adrenoceptor antagonist has antioxidant effect also.
 Minoxidil-K channel opener + release NO.
 Liquid Nitrogen temperature is -197 degree Celcius.

 Caco2, a cell line model is used to classify drug for its BCS
 Classification bleomycin & nitrosourea coming under cycle nonspecific anticancer Agent
 All xanthophylline act on Adenosine receptor except enrophylline.
 Omalizumab used in asthma, it is anti IgE antibody.
BIOCHEMISTRY IMPORTANT PINPOINTS

 A living cell is true representative of life with its own organization & specialized Functions.
 Accumulation of lipofuscin, a pigment rich in lipids and proteins, in the cell has been
Implicated in ageing process.
 Leakage of lysosomal enzymes into the cell degrades several functional
macromolecules and this may lead to certain disorders (e.g. arthritis).
 Zellweger syndrome is rare disease characterized by the absence of functional peroxisome.
 Lysosomes are the digestive bodies of the cell, actively involved in the degradation of
Cellular compounds. Peroxisomes contain the enzyme cataloes that protects the cell
from the toxic effects of H2O2.
 The cellular ground matrix is referred to as cytosol which, in fact, is composed of a
network of protein filaments, the cytoskeleton.
 Mutarotation: The  and  Anomers of glucose have different optical rotations.

The specific optical rotation of a freshly prepared glucose ( anomer) solution in
water is +112.2o which gradually changes and attains an equilibrium with a constant
value of +52.7 o. ln the presence of alkali, the decrease in optical rotation is rapid. The
optical rotation of p-glucose is +18.7o (19 o)
 Mutarotation of fructose: Fructose also exhibits Mutarotation. Ln case of fructose,
the pyranose ring (six-membered) is converted to furanose (five-membered) ring, till
an equilibrium is attained. And fructose has a specific optical rotation of -92o at
equilibrium
 von Gierke's disease (type ii): The incidence of type I glycogen storage disease
is 1 per 200,000 persons. It is transmitted by autosomal recessive trait. This disorder
results in various biochemical manifestation
 Anderson's disease (amylopectinosis): A rare disease, glycogen with only few
branches accumulate; cinhosis of liver, impairment in liver function.

 Pompe's disease: Glycogen accumulates in lysosomes in almost all the tissues; heart
is mostly involved; enlarged liver and heart, nervous system is also affected; death
occurs at an early age due to heart failure.
 Cori's disease: Branched chain glycogen accumulates; liver enlarged; clinical
manifestations are similar but milder compared to von Gierke's disease.
Distinct deficiency conditions of certain b-complex vitamins are known
VITAMIN DEFICIENCY
Thiamine Beriberi
Niacin Pellagra
Riboflavin Cheilosis, glossitis
Pyridoxine Peripheral neuropathy
Folic acid Macrocytic anemia
Cobalomin Pernicious anemia
 B-complex vitamin deficiencies are usually multiple rather than individual with
overlapping symptoms.
 A combined therapy of vitamin B12 and folic acid is commonly employed to treat the
patients of megaloblostic anaemias.
 Megodoses of niacin are useful in the treatment of hyperlipidemia.
 Long term use of isoniazid for the treatment of tuberculosis causes 86 deficiency.
 Folic acid supplementation reduces elevated plasma homocysteine level which is
Associated with atherosclerosis and thrombosis.
 Sulfonamides serve as antibacterial drugs by inhibiting the incorporation of PABA to
produce folic acid.
 Aminopterin and amethopterin, the structural analogues of folic acid, are employed in
the treatment of cancers.
 Lipoic acid is therapeutically useful as an antioxidant to present stroke, myocardial
infarction, etc.

Colour reactions of proteins/amino acids Reaction Specific group or amino acid
REACTION SPECIFIC GROUP OR AMINO ACID
Biuret reaction Two peptide linkages
Ninhydrin reaction -Amino acids
Xanthoproteic Reaction Benzene ring of aromatic amino acids (Phe, Tyr, Trp)
Millons reaction Phenolic group(Tyr)
Hopkins-Cole Reaction lndole ring (Trp)
Sakaguchi reaction Guanidino group (Arg)
Nitroprusside reaction Sulfhydryl groups (Cys)
Sulfur test Sulfhydryl groups (Cys)
Pauly’s test Imidazole ring (His)
Folin coicalteau's test Phenolic groups (Tyr)
DRUGS OF CHOICE
1. Paracetamol poisoning- acetyl cysteine
2. Acute bronchial asthma: - salbutamol
3. Acute gout: - NSAIDS
4. Acute hyperkalemia: - calcium gluconate
5. Severe DIGITALIS toxicity: - DIGIBIND
6. Acute migraine: - sumatriptan
7. Cheese reaction: - phentolamine
8. Atropine poisoning: - physostigmine
9. Cyanide poisoning: - amyl nitrite
10. Benzodiazepine poisoning: - flumazenil
11. Cholera: - tetracycline
12. KALA-AZAR:- lipozomal amphotericin- B
13. Iron poisoning: - desferrioxamine
14. MRSA: - vancomycin
15. VRSA: - LINEZOLID

16. Warfarin overdose: - vitamin-K (NIPER- 2009)

17. OCD: - fluoxetine
18. Alcohol poisoning: - fomepizole
19. Epilepsy in pregnency: - Phenobarbitone
20. Anaphylactic shock: - Adrenaline
21. MRSA Infection-Vancomycin
22. Malaria in Pregnancy-Chloroquine
23. Whooping Cough or Pertussis- Erythromycin
24. Kawasaki disease-IV Ig
25. Warfarin Overdose-Vit-K
26. Heparin Overdose-Protamine
27. Hairy Cell Leukemia-Cladirabine
28. Multiple Myeloma- Melphalan
29. CML-Imatinib
30. Wegner's granulomatosis-Cyclophosphamide
31. HOCM- Propranolol
32. Delirium Tremens-Diazepam
33. Drug Induced Parkinsonism-Benzhexol
34. Diacumarol Poisoning-Vit-K
35. Type-1 Lepra Reaction-Steroids
36. Type- 2 Lepra Reaction-Thalidomide
37. Allergic Contect Dermatitis-Steroids
38. PSVT- 1st-Adenosine, 2nd-Verapamil, 3rd-Digoxin
39. Z-E Syndrome- Proton Pump Inhibitor
40. Chancroid-Cotrimoxazole
41. Dermatitis Herpetiformis-Dapsone
42. Spastic Type of Cerebral Palsy-Diazepam
43. Herpis Simplex Keratitis-Trifluridine
44. Herpes Simplex Orolabialis-Pancyclovir
45. Neonatal Herpes Simplex-Acyclovir
46. Pneumocystis carinii Pneumonia- Cotrimoxazole for Nodulo
47. Cystic Acne- Retinoic acid
48. Trigeminal Neuralgia-Carbamezapine
49. Actinomycosis-Penicillin

50. Plague- Streptomycin

51. Opioid Withdrawal- Methadone 2nd-Clonidine
52. Alcohol Withdrawal- Chlordiazepoxide 2nd-Diazepam
53. Post Herpetic Neuralgia- Fluphenazine
54. WEST Syndrome-ACTH
55. Diabetic Diarrhoea- Clonidine
56. Lithium Induced Neuropathy-Amiloride Communicable Disease:
57. Tetanus: PEN G Na; TETRACYCLINE; (DIAZEPAM
58. Diphteria: PEN G K; ERYTHROMYCIN
59. Pertusis: ERYTHROMYCIN; AMPICILLIN
60. Meningitis: MANNITOL (osmotic diuretic); DEXAMETHASONE (anti-inflammatory);
DILANTIN/PHENYTOIN (anti-convulsive); PYRETINOL/ENCEPHABOL (CNS stimulant)
61. Cholera: TETRACYCLINE
62. Amoebic Dysentery: METRONIDAZOLE
63. Shigellosis: CO-TRIMOXAZOLE
64. Typhoid: CHORAMPHENICOL
65. Rabies: LYSSAVAC, VERORAB
66. Immunoglobulins: ERIG or HRIg
67. Malaria: CHLOROQUINE
68. Schistosomiasis: PRAZIQUANTEL
69. Felariasis: DIETHYLCARBAMAZINE CITRATE
70. Scabies: EURAX/ CROTAMITON
71. Chicken pox: ACYCLOVIR/ZOVIRAX
72. Leptospirosis: PENICILLIN; TETRACYCLINE;
ERYTHROMYCIN
73. Leprosy: DAPSONE, RIFAMPICIN
74. Anthrax: PENICILLIN
75. Tuberculosis: R.I.P.E.S.
76. Pneumonia: COTRIMOXAZOLE; Procaine, Penicillin
77. Helminths: MEBENDAZOLE; PYRANTEL, PAMOATE
78. Meningitis: MANNITOL (dec. ICP); DEXAMETHASONE (relieve cerebral edema);
DIAZEPAM (anticonvulsant); PENICILLIN
79. Syphilis: PENICILLIN
80. Gonorrhoea: PENICILLIN

Classification of antimicrobial agents: On the basis of their mechanism of action

Antimicrobial agents are used for the treatment of the microbial infections in the body and
the treatment is termed as chemotherapy. Paul Ehlrich is known as the father of
Chemotherapy who used Arsphenamine for the treatment of Syphilis. Chemotherapy is an
important perspective for the student’s GPAT preparation as lots of questions are asked from
this section. Here, we are introducing the classification of antimicrobial agents on the basis of
their mechanism of action.
Classification of antimicrobial agents

1. Antibiotics that inhibits Bacterial Cell Wall synthesis
 Pencillins,
 Cephalosporins
 Carbepenam
 Monobactam
Mechanism:
These drugs inhibit the transpeptidase enzyme used in the bacterial cell wall synthesis.
 Vancomycin
Mechanism:
This drug makes complex with C-terminal D-alanine residues of peptidoglycan precursors.
 Cycloserine
Mechanism:
It inhibits alanine racemase and D-alanyl-D-alanine synthetase.
2. Antibiotics that inhibit Ribosome function and prevent protein synthesis

a) Aminoglycosides: It causes misreading in mRNA
b) Tetracyclines: This class of drug binds with 30S ribosomes and inhibits the binding of
aminoacyl-tRNA into the A site of the bacterial ribosome.
c) Chloramphenicol: It binds with the peptidyl transferase enzyme on the 50S ribosome and
inhibits protein synthesis.
d) Spectinomycin
e) Azithromycin and Clarithromycin: Inhibits translocation which leads the protein
synthesis inhibition.

3. Antibiotics that affect the function of cytoplasmic membranes

a) Antifungal drugs:
 Amphotericin B
 Ketoconazole
 Clotrimazole
 Fluconazole
 Miconazole
 Nystatin.
b) Bacitracin & Polymyxin B & E:
They cause the leaking of nuclear material which leads to the cell death.
c) Gramicidin: It produces aqueous pores in the cell membrane.
4. Antibiotics that inhibit Nucleic acid synthesis
a) Agents that interfere with Nucleotide synthesis:

 Zidovudine: DNA polymerase inhibition.
 Acyclovir: Thymidine kinase and DNA polymerase inhibition of Herpes virus.
 Flucytosine: Thymidylate synthetase inhibition.
b) Agents that interfere with DNA replication:
 Metronidazole: DNA strand breakage by the reduced Nitro group.
 Quinolones: DNA gyrase inhibition
c) Agents that inhibit RNA polymerase:
 Rifamycin
d) Agents that interfere with the precursor synthesis:
Sulfonamides: Inhibit the conversion of Pteridine & p-Amino Benzoic acid (PABA) into
dihydrofolic acid.
Trimethoprim: Inhibits the conversion dihydrofolic acid into tetrahydrofolic acid.
e) Agents that interfere with the Template function of DNA:
ALL THE BEST

DO THIS FIST MATERIAL WELL ALL IMP POINTS ARE INCLUDED
REVISE THEM DAILY: AMAR RAVAL

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 PHARMAROCLOGY MASTER GPAT NOTES
PHARMACOLOGY GPAT NOTES PHARMAROCKS

Pharmacodynamics : - What drug does to body.
Pharmacokinetics : - What body does to the drug.
Pharmacotherapeutics : - Use of drugs in prevention & treatment of disease.
Clinical pharmacology : - Scientific study of drugs in man.
Toxicology : - Aspect of pharmacology deals with adverse effects of

Drugs.
Pharmacodynamic agents : - Designed to have pharmacodynamic effects in the

recipient.
Chemotherapeutic agents : - Designed to inhibit/kill parasites/malignant cells & does not

have or with minimal pharmacodynamic effects in recipient.
Orphan drugs : - Drugs or Biological Products for diagnosis/treatment/

Prevention of a rare disease.
E.g.:- Liothyronine (T3), Desmopressin, Baclofen, Digoxin Antibody.
Routes of drug Administration

1) Oral 2) Parentral
Injections:-
A) Intradermal: - given in to layers of skin. E.g.:- BCG vaccine, for testing drug
sensitivity.
B) S.C:- Only non-irritant drug are given absorption can be enhanced by enzyme
Hyalurinase S.C.drug implants can act as depot therapy. E.g.:- steroid hormones.
In children saline is injected in large quantities – Hypodermalysis.
C) I.M:- Mild irritants, suspensions & colloids can be injected by this route.
D) I.V:- Directly to vein.
E) Intra arterial: - Only used for diagnostic studies. E.g.:- Angiograms, embolism
therapy.
F) Intrathecal: - Spinal anaesthetics in to subarachinoid space.
G) Intra medullary: - Drug introduced to Bone marrow.
H) Intra articular & Intra tensional: - Drug administered into joints. E.g.:- Hydrocortisone
acetate in rheumatoid arthritis.

PHARMACOKINETICS
Absorption of Drugs:-
A) Simple diffusion: - Bidirectional process rate of transfer across the membrane is

proportional to concn gradient. E.g.:- H20 soluble drugs with low mol-wt, lipid
soluble drugs.
B) Active transport: - requires energy – independent of physical properties of
membrane. E.g.:- H20 soluble drugs with high mol-wt.
Carrier mediated transport: - E.g.:- Intestinal absorption of Ca2+.
C) Pinocytosis: - Important in unicellular organisms like Amoeba.
Bioavailability: - Amount of drug reaches systemic circulation following a non-vascular

drug administration.
AUC Oral
F = AUC IV
Barriers:-
B.B.B:- made up of choroid cells (strong Barrier).
Testis Barrier: - made up of seroid cells.
Placental Barrier: - made up of sertoli cells (weak Barrier).
Endothelial Barrier: - in all blood cells (very weak).
For absorption of vitB12, IF factor is required which is synthesized by parietal cells?
Solubility of drugs:-
Ionized form – soluble
Unionized form – more absorbed
Distribution of drugs:-
Plasma protein binding: - many drugs have affinity towards plasma proteins, Acidic drugs
towards Albumin, Basic drugs towards acid Glycoprotein, Prothrombin, and Thromboplastin.
Radioligand binding: - is used to determine drug in protein complex.
1
PPB Vd
Tissue storage of drugs:-
Skeletal muscle, Heart: - Digoxin, emetine
Liver: - Chloroquine, tetracycline’s, digoxin
Kidney: - Chloroquine, digoxin, emetine
Thyroid: - Iodine
Brain: - CPZ, Acetazolamide, Isoniazid
Retina: - Chloroquine
Iris: - Ephedrine, Atropine
Bone & Teeth: - Heavymetals, Tetracycline’s
Adipose tissue: - Phenoxy Benzamine, Minocycline, ether, Thiopentane.
Metabolism of drugs :- ( Biotransformation / Detoxification)

Chemical alteration of drug in physiological system
1. Inactive form
2. Active metabolite, E.g.:- Codeine to morphine
3. Prodrug to active drug, E.g.:- L-Dopa to Dopamine

Phase I metabolism: - Nonsynthetic
Reaction Enzyme Examples

Oxdn Monooxygenases cytp450 in lives Drugs with “OH” & “COOH”groups
Redn Reductases Halothane, trichloroethand
Hydrolysis Esterases Lidocaine procainide Benzocaine

Cyclisation Proguanil to cycloguanil
Decyclisation Phenobarbitone & Phenytoin
Phase II Metabolism: - Synthetic or Conjugation
Conjugation Endogenous substrate Examples

1. Glucouronide Glucouronic acid (glucose) “Oh” & “COOH” group drugs
2. Acetylation Acetyl co-A (Citric acid “NH2” & Hydrazine group drugs
cycle)
3. Methylation Methionine “NH2” & Phenol group drugs
4. Sulphate Sulfokinases Phenolic compds & Steroids
5. Glycine(rarely Glycine Salicylates & “COOH” group drugs
occur)
6. Glutathione Paracetamol
7. Ribonucleotide Purine & Pyrimidine
antimetabolites
Prodrug Active form Active drug Active Metabolite

Levodopa Dopamine Chloralhydrate Trichloroethanol
Enalpril Enalaprilat Phenacetin Paracetamol
L-Methyldopa L- Primidone Phenobarbitone
Methylnorepinephrine
Dipivefrine Epinephrine Digitoxin Digoxin

Benorylate Aspirin+Paracetamal Codeine Morphine
Proguanil Proguanil triazine Spironolactone Canrenone
Prednisone Prednisolone Amitryptiline Nor-tryptiline
Becampicillion Ampicillin Diazepam Desmethyl diazepam,
oxazepam
Sulphasalazine 5-amino salicylic acid Trimethadione Dimethadione

Microsomal enzymes: - These are inducible by drugs, diet E.g.:- cytP450, Monooxygenases,
Glucouronyl transferase etc.
Catalyses many oxdn, redn, Hydrolysis & glucouronide conjugations.
Non Microsomal enzymes: - E.g.:- Flavoprotein oxidases, esterases, amidases & conjugases.
Catalyses some oxdn & redn, many hydrolytic reactions & all conjugations except
glucouronidation.
Hofmann elimination: - Inactivation of drug in body fluids by spontaneous molecular

rearrangement without enzymes. E.g.:- Atracurium.
Enzyme inducers: - Phenytoin, Barbiturates, Rifampicin, Carbamazepine.
Enzyme Inhibitors: - Cimetidine, erythromycin, chloramphenicol, ciprofloxacin, MAO

inhibitors, sulfonamides, verapamil, INH, Disulfiram etc.
Excretion of drugs: - elimination of drug in inactive form,

Urine – H20 soluble drugs, Feces – Unabsorbed drugs (complex drugs insoluble drugs),
Swets – salts & heavy metals,
Saliva – Hm, Lead, SCN, Lithium, & Tetracycline’s,
Lungs – gaseous drugs, Alcohol paraldehyde etc.,
Lacrimal – drugs applied to eye.
Rate of elimination
Clearance = plasma concn of drug
PHARMACODYNAMICS
Drug produces action by stimulation, depression, irritation, replacements cytotoxic action.

Mechanism of drug action:-
Properties Drugs
Physical Mass of drug Bulk laxatives, protectives
Adsorptive property charcoal, kaolin
Osmotic activity mgso4, mannitol
Radioactivity I131 & other isotope
Radio opacity Baso4, urografin
Chemical Neutralizing Antacids
germicidal Knmo4, I2
chelating EDTA, Penicillamine
Through enzymes: - Drugs may also increase or decrease rate of enzymatically mediated
reactions.
Stimulation: - e.g.:- Adrenaline stimulates Adenyl cyclase pyridoxine increases
decarboxylase activity.
a) Inhibition :-
1) Non specific inhibition: - Many drugs act by denaturing proteins. E.g.:- Hm, Acid &
Alkalies, Alcohol, Formaldehyde, Phenol etc.

2) Specific inhibition :-
i) Competitive: - Physostigmine & neostigmine with Ach for sulfonamides with
PABA for folatesynthetase Allopurinol with Hypoxanthine for xanthine oxidase
carbidopa & methyldopa with L – Dopa for dopa decorboxylase.
ii) Non-competitive:- Ach & Papaverine on smooth muscles Ach & Decamethionine
on NmJ.
Through receptors:-
1) Clark-Arheneous theory (occupation theory):- The effect of drug is proportional to

fraction of receptors occupied by drug & maximum effect results when all receptors
are occupied.
2) Raton’s theory (Rate theory):- The effect of drug is a function of receptor occupation
& the rate of drug receptor combination. Here response depends on rate of
Association between drug molecule & receptor.
G proteins are Heterotrimeric proteins involved in receptor transduction it has 3 subunits.
PAx = - log (A) x,

PA2 = - log (A) 2,
PD2 = - log (a) 2,
Where (A) = molar concn of antagonist, where (a) = molar concn of against.
Eudismic ratio: - ratio of the activities of active enantiomer (eutomer) and inactive
enantiomer (distomer) in chiral pharmocodynamics.
AUTONOMIC NERVOUS SYSTEM
Sympathetic or Adrenergic system enables the individual to adjust to stress & prepares the
body for ‘Fight or Flight’ response.
Parasympathetic or Cholinergic mainly participate in tissue building reactions.
Both sympathetic & parasympathetic nervous system consists of myelinated preganglionic
fibre which forms a synapse with the cell body of non-myelinated post ganglionic fibre.
Synapse: - It is the structure formed by the close opposition of a neuron either with another
neuron or with effector cells.
The synapse b/w preganglionic & postganglionic fibres is termed as Ganglion
The synapse b/w postganglionic &receptors is termed as Neuroeffector junction.
Neurohumoral transmission: - The transmission of an impulse across the synapse in central

& peripheral nervous system occurs as a result of release of a neurohumoral transmitter
substance in to the synaptic cleft.
Junctional transmission: - The arrival of an action potential at the axonal terminals initiates
the series of events that put in to effect neurohumoral transmission of an excitatory/inhibitory
impulse across the synapse / neuroeffector junction.

ADRENERGIC RECEPTORS:-
Receptor Agonist Antagonist Tissue Response Molecular

mechanism
a1 Methoxamine Quinazoline Blood vessel Vasoconstriction Stimulation of

derivatives Smooth muscle Contraction phospholipase-
( Prazosin) Liver Increased blood C & formation
glucose level of IP3 /DAG
a2 Clonidine Yohimbine. Islet cells Decreased insulin Inhibition of

Raulosine Platelets Aggregation Adenylcyclase
Vascular Contraction & neuronal
smooth muscles ca2+ channels
b1 Dobutamine Atenolol, Heart +ve Inotropic Activation of

Acebutolol, Juxta actions Adenylcyclase
Bisoprolol, glomerular cells Increased rennin
Metoprolol release
b2 Terbutaline, Butoxamine Smooth Relaxation Activation of

salbutamol Methyl muscles Adenylcyclase
Propranalol
b3 Sibutramine -------------- Adipose tissue Lipolysis Activation of

(Antiobesity) Adenylcyclase
Adrenergic receptors are membrane bound G- Protein coupled receptors which function
primarily by increasing/decreasing the intracellular production of secondary messengers’
cAMP/IP3- DAG. In some cases the activated G-Protein itself operates K+/Ca2+ channels or
increases prostaglandin production.
Classification of Adrenergic drugs:-
A. Therapeutic classification-
1. Pressor drugs: - Adrenaline, NA, Metarminol
2. Inotropic agents: - Dopamine, Dobutamine, Isoprenaline& Xamoterol
3. CNS Stimulants:-Amphetamine
4. Smooth muscle relaxants:-Adrenaline, Isoprenaline, Isoxsuprine& b2 stimulants
(Salbutamol)
5. Drugs used in allergy: - Adrenaline & ephedrine
6. Local vasoconstrictor effect:-Adrenaline, Naphozoline, Phenylephrine
7. Nasal decongestants: - Oxymetazoline, Tuaminoheptanesulfate
8. Anorectics: - Fenfluramine, dexfenfluramine&Phenteramine
9. Antiobesity: - Sibutramine

B.Chemical classification:-
1. Catecholamines – Adrenaline, NA, Dopamine, 5-HT & Isoprenaline
2. Non-Catecholamines – Amphetamine, Ephedrine, Isoxsuprine, Mephentamine
Pharmacological Actions:-
1. Heart: - Due to its stimulant action on b1 receptors causes +ve inotropic actions. This is
associated with increased metabolism of myocardium & increased O2 consumption, thus
decreasing cardiac efficiency.
2. Blood vessels: - Raises systolic B.P. by its cardiac actions lowers diastolic B.P. by its
peripheral actions & hence not suitable in Hypotensive shock
 In moderate doses rise in B.P. is followed by a fall as it activates both the receptors.
This is called as ‘Biphasic response’.
 By prior administration of a blockers (ergot) leads to stimulation of only b2 receptors
& thus causes a fall in B.p. This phenomenon is called as ‘Dale’s vasomotor reversal’
Compared to Adrenaline, the NA has feeble actions on b2 receptors.
3. Smooth muscles: - relaxes bronchial muscles

Produce contraction of spleemic capsule producing a release of erythrocytes in to the
Peripheral circulation. This serves as protective mechanism during stress such as hypoxia &
Hemorrhage
4. Eye: - Mydriasis due to contraction of radial muscle fibres of IRIS. On topical application
do not produce Mydriasis but cause reduction in intraocular tension.
5. Respiration: - Bronchodilator & weak stimulant
6. Metabolic effects: - Increases Blood glucose, Blood lactate, free fatty acids. Inhibits
insulin release.
7. CNS: - Catecholamines cannot cross BBB
8. Miscellaneous: - Skeletal muscle contraction, Accelerates Blood coagulation, Platelet

aggregation, Leucocytosis& Eosonopenia. Inhibit cellular anaphylactic mechanism& prevent
release of allergic mediators (Histamine from mast cells)
Major excretory products are Vanillin mandelic acid
Therapeutic Uses:-
1. Na in elevating B.P. in shock
2. In glaucoma. To control hemorrhage
3. Cardiac resuscitation
4. Bronchial asthma
5. First line drug in Hypersensitivity
6. Along with Local anaesthetics to prolong their action.
Note: - Metyltyrosine/Metyrosine/2-methyl p-tyrosine inhibits Tyrosine hydroxylase in
synthesis of catecholamines & used in treatment of Pheocytochroma.

Catecholamines Non-catecholamines
Not effective orally Orally effective
Do not cross BBB Crosses BBB
Susceptible to MAO Relatively resistant to MAO
Nasal decongestants: - Most of the Sympathetic amines on topical application produce Local
vasoconstriction & used as Decongestants
E.g. Oxymetazoline, Zylometazoline, Naphozoline.tuaminoheptanesulfate
Potency of agonists at a&b receptors are-

a- Adrenaline > NA > Isoprenaline
b- Isoprenaline > Adrenaline > NA
b2 selective receptor stimulants: -

 Isoprenaline used in Asthma will cause adverse cardiac effects due to action on b1
 Therefore selective b2 stimulants are used in Asthma & as Tocolytics
 E.g.Nylidrin.Isoxsuprine
Drugs used in CCF:-

 Dopamine& Dopexamine acts on a & b receptors as well as D1 &D2 receptor.
 Dobutamine acts only on a &b receptor
 Xamoterol has selective b1 agonist action.
ADRENERGIC BLOCKING AGENTS:-
Classification:-
-Blockers:-
1. - Haloalkylamines- Dibenamine& Phenoxybenzamine

2. Imidazoline derivatives- Tolazoline& Phentolamine
3. Quinazolines- Prazosin, terazosin, tremazosin
4. Natural & dehydrogenated ergot alkaloids
5. Miscellaneous- yohimbine, Indoramine, Cpz
The receptor blockade produced by Dibenamine& Phenoxybenzamine is ir-reversible type.

Phenoxybenzamine is 6-10 times more potent than Dibenamine but has be converted to active
metabolite.
Therapeutics Uses: - In pheocytochroma, Hypertension, Secondary shock, CHF, BHP, Male

sexual dysfunction, Scorpion Bite.
-Blockers:-
1. Specific b- Blockers- Timolol, Nadolol

2. Blockers with membrane stabilizing action: - Propranalol, Oxyprenolol, Pindolol
3. Blockers with cardioselective action: - Atenolol, Acebutolol, Metoprolol&Esmolol
4. Both a &b blockers: - Labetolol, Carvedilol, Dilevilol&Medroxolol
Atenolol with poor lipid solubility does not cross BBB at all.

 Propranolol, Alprenolol&Metoprolol are metabolized by liver, Practolol is largely

excreted unchanged by kidneys.
 Pindolol, Atenolol, Acebutolol& Timolol by both the routes.
 They are contraindicated in the myocardial insufficiency, Bradycardia, Asthma,
Heartblock& Insulin dependent diabetes.
T.Uses:-Anginapectoris, MI, Cardiac arrhythmia, Hypertension, Thyrotoxicosis,

Pheocytochroma, to decrease cardiac symptoms prior to important speech/meetings.
Propranalol is useful in prevention of Migrane & treatment of Essential tumor.
CHOLINERGIC DRUGS
Ach produces its dual actions as Muscarinic actions on Muscarinic & Nicotinic actions on
nicotinic receptors.
Muscarinic receptors (mol, wt-80,000) belong to g-Protein coupled receptors. Nicotinic
receptors are Pentameric proteins.
Receptors Agonist Antagonist Tissue Response Molecular

Mechanism
Nm Phenyl D-Tc NMJ End plate Opening of
trimethyl a- Bangarotoxin depolarization cation channels
ammonia
Nn Dimethyl Trimethophan Autonomic Depolarization& Opening of
phenyl Hexamethonium Ganglia firing of Post cation channels
piperazinum Succinylcholine ganglionic neurons.
Adrenal Secretion of
medulla catecholamines
M1 Oxytremonium Pirenzepine Autonomic Depolarisation & Stimulation of
Telenzepine Ganglia Late EPSP. phospholipase-
Atropine Gastric Histamine release C & formation
Glands of IP3 /DAG
M2 Methacholine Methocrotamine Heart Negative Inotropic Inhibition of
Atropine effect Adenylcyclase
M3 Bethnecol Atropine Smooth Contraction Stimulation of
Hexahydrosilede Muscles phospholipase-
nifol Secretory Increased secretion C & formation
Glands of IP3 /DAG
CLASSIFICATION:-
1. Esters of Choline – Ach, Methacholine, Carbachol& Bethnechol
2. Cholinomimetic Alkaloids – Pilocarpine, Muscarine&Arecholine
3. Cholinesterase inhibitors –
a) Reversible: - Physostigmine (Natural), Neostigmine.Pyridostigmine, demecarium Tacrine

(Acridine) used in Alzhmeir’s disease.
b) Ir-reversible: - Di-isopropylflurophosphate (therapeutically useful), OMPP, Malathion,

Parathion, Nerve gases (Tabun, sarin& Soman) Propoxur (carbamates)

Pharmacological actions:- Undergoes Hydrolysis in Neutral or Alkaline medium & hence

preserved in Acidic medium.
On oral administration gets destroyed by GIT & hence given by I.v.
There is no circulating Ach in the Blood.
Muscarinic actions –
1. CVS: - Negative Inotropic actions, Dilates Blood vessels, Coronary arteries&veins.
Increases tone & rhythmic activity of smooth muscles of GIT & enhance Peristalsis.
2. Secretions: - Increases Nasal, Bronchial, Gastric, salivary, Pancreatic & Intestinal

secretions.
3. Eye: - on instillation no effect. But on injection to carotid arteries produces-

Constriction of Pupil (Miosis) – By contracting circular fibres of sphincter pupillae
Spasm of accommodation – Due to contraction of ciliary muscle, resulting in relaxation of
suspensory ligament of lens.
Nicotinic actions –
1. Increases output of Ach&NA from Post ganglionic sympathetic & Parasympathetic nerve
endings & increases B.p.
2. Produce paralysis of skeletal muscles at NMJ
Contraindications of choline esters: - Hyperthyroidism, Bronchial asthma, Peptic ulcer& MI
T.Uses: - Glaucoma, Post operative paralytic ileus & abdominal distension
Anticholinesterases: - they act by inhibiting true & Pseudo cholinesterases, thus causing
accumulation of Ach at various sites.
MOA: - Ach is inactivated by combination of 2 sites on enzyme Cholinesterase.

Anionic site bearing –ve charge attracts Quaternary nitrogen atom of Ach
Esteratic site which attracts carboxylic acid group of Ach. As a result of union of Ach with
cholinesterase the esteratic site of enzyme is acetylated & this results in splitting of choline.
The acetyl group in combination with esteratic site is However immediately removed as a
result of combination with water forming Acetic acid.
This sets esteratic site of enzyme free for further inactivation of Ach.
Reversible Anticholinesterases: - These are structurally similar to Ach & combine with
Anionic & esteratic sites of cholinesterase as well as with Ach receptor. However the
complex with esteratic site is much readily hydrolysed compared to Ach. This produces
temporary inhibition of the enzyme.
Uses – Glaucoma, Myasthenia gravis, Snake venomPoisonimg, Curare Poisoning&
Alzhmeir’s disease.
Ir-reversible: - These organophosphorous compounds combine only with esteratic site of

cholinesterase & consequently esteratic site is phosphorylated. The hydrolysis of esteratic site
is extremely slow /does not occur at all.
This will lead to Morbidity & Mortality, to overcome this we use cholinesterase reactivators
like Pralidoxime, Diacetylmonoxime&Obidoxime chloride.

Note: - Edrophonium forms reversible complex only with Anionic site & Hence shorter
duration of action.
Echothiopate forms complex with both Anionic & esteratic sites & hence is much more
potent than other compounds.
ANTI-CHOLINERGIC DRUGS
They Block only Muscarinic actions but not the Ganglionic & skeletal neuromuscular actions
of Ach.
Classification:-
1. Natural alkaloids – Atropine, Scopalamine
2. Semisynthetic derivatives – Homatropine, Ipatropium
3. Synthetic compounds – a) Mydriatics: - Cyclopentolate, Tropicamide
B) Antisecretory: - Propantheine, Pirenzepine
MOA: - Belladonna alkaloids block muscarinic effects of Ach. The antagonism is of

competitive type which is reversed by an increase in Ach concentration at the cholinergic
nerve endings
P.actions:- Atropine & scopolamine have qualitatively similar actions except that Atropine is
CNS stimulant While Scopalamine is CNS Depressant.
1. Secretions – Decreases gastric secretions including total acidity & enzymes, leading to
decreased motility
Decreases Nasal, Bronchial & other secretions
2. Smooth muscles – Relaxation,

Causes Urinary retention
3. Eye - Mydriatic (1%), ciliary smooth muscle is paralyzed& produces tightening of

suspensory ligament resulting in flattening of lens with consequent increase in focal length.
Thus individual is able to see only at long distance (paralysis of accommodation/cycloplegia)
Because of sphincter paralysis he cannot constrict the pupils for viewing near objects clearly
in response to Bright light (Photophobia).
4. CNS – Atropine due to stimulation of medullary vagal nuclei & higher cerebral centers
produces bradycardia, increase rate & depth of respiration produced by Anticholinesterases.
Scopolamine by S.C.depresses RAS & Produces euphoria, Amnesia & dreamless sleep.
Therapeutic uses:-
 To control hypermotility, Colicky pain
 Organophosphorous compound poisoning
 As Antisecretory in Pre anaesthetic medication, Peptic ulcer& pulmonary embolism
 Motion sickness (scopolamine)
 Parkinsonism
 As Mydriatic& cycloplegic
 As Antispasmodic in drug induced diarrhoea, Spastic constipation,
Gastritis&Dysmenorrhoea.

Contraindications:-
 May cause Congestive glaucoma in patients over 40yrs
 CCF with tachycardia
 Pyloric obstruction, pylorospasm&Cardiospasm
Ganglionic Stimulants: -
1. Nicotine, lobeline
2. Synthetic compounds (TMA, DMPP)
Activation of Nicotinic receptors facilitate the release of Ach, NA, dopamine, 5-HT & b Endorphin
 Nicotine releases GH, Prolactin & ACTH
 Increases muscle twitching followed by paralysis of myoneuronal transmission
 Induces Hepatic microsomal enzymes
 Increases BMR, reduces body weight & Appetite
 Causes lipolysis & releases free fatty acids Excessive release of cortisol affect mood
& contribute to Osteoporosis
 Vomitting due to action on CTZ, releases ADH by stimulating Supraoptic nuclei of
Hypothalamus
 Acidic urine Increases excretion of free nicotine, TMA & DMPP are excreted unchanged
 A.R:- Bronchitis, Emphysema, Tobacco Amlobia
Cigarette contains – Nicotine, Pyridine.CO, Furfural, Volatile acids& polycyclic hydrocarbons
Antidepressant like Bupropion is used to quit smoking in some individuals.
Note: - Mydriatics – Homatropine, Eucatropine & cyclopentolate

Other Antimuscarinics – Atropine methanitrate, Methoscopalmine bromide/Nitrates
Propantheline (probanthine) – used in peptic ulcer
Methantheline (Banthine), Dicyclomine
Pirenzepine (Gastrozepin) – in duodenal ulcer
Flavoxate (Uripas) & Oxybutynine (Ditropan) – In Dysurea,
In urinary frequencies Tolteridine – M3 antagonist in Urinary incontinence.
Ganglionic Blocking agents: - Blocks transmission across Autonomic ganglia (Both

sympathetic & Parasympathetic)
E.g.Hexamethonium, trimethomine&Hexamylamine
Skeletal muscle relaxants: - Used to treat spasm/spasicity

 Spasm – Involuntary contraction of muscle or group of muscles usually accompanied
by pain & limited function.
 Spasticity – due to increased skeletal muscle tone associated with decrease in skeletal
muscle power due to damage to the corticonotoneuronic pathways as in CNS injury,
cerebral palsy, stroke or Multiple sclerosis.
Classification:-
1. Drugs acting centrally – diazepam, Baclofen& Mephenesin
2. Drugs acting peripherally at NMJ –
a) Competitive Blockers: - D-TC,
b) Depolarization blockers: - Succinyl choline
c) Inhibitors of release of Ach from the motor nerve terminals: - Botulinum
Toxin – A & Antibiotics (Tetracycline& Aminoglycosides)
3. Drugs directly acting on Skeletal muscles: - Dantrolene

PHYSIOLOGY OF SKELETAL MUSCLE CONTRACTION:-
1. Due to nerve action potential releases Ach from synaptic vesicles of motor nerve in to
synaptic cleft in large quantities, While in absence of NAP Ach is released due to miniature
end plate potential ( MEPP ) in small quantities.
2. The released Ach binds to nicotinic receptors on the motor endplate resulting in Localised
depolarization & development of End plate polarization (EPP). Depolarization is due to
influx of Na+ & Efflux of K+ ions from motor endplate.
3. When EPP is achieved the surround area of muscle fibre gets excited resulting in
development of muscle action potential (MAP) which initiates contraction of a muscle as a
result of release of ca2+ in to the Sarcoplasm.
4. Ach is metabolized enabling repolarisation of motor endplate& muscle fibre membrane.

This is achieved by reversal of ionic fluxes. The polarized muscle is now capable of
responding to fresh nerve impulse.
Skeletal muscle contraction can be blocked as follows –
1. Blocking transmission of impulse across the motor nerve – local anaesthetics

2. Inhibit the synthesis of Ach in motor nerve – Hemicholinum
3. Inhibit the release of Ach – Botulinum Toxin-A & antibiotics (tetracyclines& Aminoglycosides)
4. Modifying the motor endplate so that it does not respond to Ach – dantrolene
D-Tc: - dextrorotatory, quaternary ammonium alkaloid from Chondrodendron Tomentosum

Relaxes smooth muscles, Releases Histamine
On repeated Administration produces cumulative toxicity. Do not cross BBB & Placental Barrier.
Di-Methyl Tubocurarine has slightly longer duration of action
Other drugs: - Alcuranium Chloride- Similar to D-Tc

Pancuranium & Atracuranium – 5 times more potent than D-Tc
Vercuranium Similar to Pancuranium but duration of action is less.
Gallamine – Similar to D-TC, less potent completely excreted by Kidneys in Unchanged form.
DRUGS USED IN PARKINSONISM
Extra pyramidal motor disorder characterized by Rigidity, tremor & Akinesia.

Here Dopamine level decreases (responsible for Akinesia) & Ach level increases (Rigidity, Tremor).
Pathology: - There is a degeneration of neurons in substantial nigra & Nigrostatial

(Dopaminergic) Tract. The cause for this degeneration is due to the formation of free radical
(Metabolism of Dopamine by MAO-B). In normal Protective mechanisms Free radical are
quenched by glutathione & other protective mechanisms. If this fails the free radical will
cause DNA damage.
A synthetic toxin n-methyl 4-phenyl tetrahydropyridine is responsible for damage to
Nigrostatial tract.

CLASSIFICATION:-
A. Drugs acting on dopaminergic system:-
1. Precursors of dopamine – L-Dopa

2. Drugs inhibit Dopamine Metabolism – A) Mao inhibitors: - Selelegine
B) Comt inhibitors:-Tolcapone& Entacapone
3. Drugs that release dopamine – Amantidine
4. Dopamine agonists – Bromocryptine, Lysuride, ropinrole, Pergolide, Pirebedil
B. Anticholinergics: - Trihexyphenidyl, Benzohexol, Benzatropine

C. Antihistaminics: - Promethazine
L-Dopa:-
 Pharmacologically inert, while its metabolite is active.
 Only 1% enters CNS, Most of the drugs get decarboxylated in GIT& liver
 It is excreted in urine partly unchanged& partly as Homovanilic acid.
 Gives Positive Comb’s test even though hemolytic anemia is not reported.
 Blood urea nitrogen & SGOT show a transient rise.
Contraindications:-
 Pyridoxine accelerates Peripheral decarboxylation of L-DOPA.
 Reserpine & Phenothiazines block the effects of dopamine to which L-Dopa is converted.
 Methyldopa intensifies the adverse effects of L-Dopa.
 Anticholinergics increase the stay of L-dopa in stomach & increase its degradation &
hence if needed must be taken 2hrs before taking L-Dopa.
Dopa decarboxylase inhibitors (DCI):-

 Pharmacologically inactive but on combined administration with L-Dopa they do not
enter BBB But decreases peripheral decarboxylation Of L-Dopa
E.g. Carbidopa, Benserazide
L-dopa – Carbidopa combination results in control of symptoms smoother, dose of L-

dopa Can be reduced up to 75%, Pyridoxine does not antagonize the actions of L- Dopa.
Selelegine (Deprenyl):- Inhibits MAO-B (responsible for dopamine metabolism)

L-dopa – Carbidopa – Selelegine combination must be avoided.
Note – MAO-A is responsible for Oxidative deamination of NA & 5-HT.
Amantidine: - Liberate dopamine from residual intact nerve endings & produces rapid
response than L-Dopa.
Dopamine Agonists: - Crosses BBB & need not to be converted to active metabolite.
Causes nausea& severe neuropsychatric adverse effects.

CENTRAL NERVOUS SYSTEM
Drugs act on CNS in following ways:-

1. They may act directly on neurons & modify neuronal functions.
2. They may act reflexly by sending afferent impulses to the CNS via chemoreceptors,
Baroreceptors & peripheral nerves.
3. They may affect the nutrition & oxygen supply of the CNS by altering its Blood
supply or affecting its metabolism.
Neurotransmitters: - Which stimulate/Inhibit the post synaptic neurons after a brief latency
& have short duration of action.
Amines – Ach, NA, 5-HT, Histamine& Dopamine
Aminoacids – l-Glutamic acid, Aspartic acid, GABA &Glycine
Peptides – Substance-P, Cholecytokinin
Note: - Glutamate & Aspartate are excitatory amino acids. While GABA is inhibitory aminoacid.
Neuromodulators: - which act on the post synaptic neurons with a longer latency, have a
longer duration of action & modify the responsiveness of the target neurons to the action of
the neurotransmitters.
Aliphatic Alcohols:-
 Ethanol in 70% acts as antiseptic, in 40-50% as rubifacient & mild irritant action
 By dissolving in the lipid membrane of the neurons & altering the functions of ion
channels & other proteins. It increases GABA-mediated synaptic inhibition. It also
inhibits NMDA glutamate receptors. & depress CNS in descending order.
 Impairs Gluconeogenesis, Reduces synthesis of Albumin & Transferrin, Increases synthesis
of VLDL with consequent Hypertriglyceredemia&Diminishes fatty acid oxidation.
 Alcohol causes liver damage & cause Cirrhosis. Elevated Gamma glutamyl
transpeptidase (GGTP) is the most sensitive indication of Alcohol liver disease.
 Uses: - Appetizer, in methanol poisoning.
Treatment of Acute alcohol poisoning: - I.v glucose 50%,

I.v. Thiamine 100mg (Bolus), I.v. MgSo4 2-4gm
Treatment of Chronic alcoholism: - Disulfiram (Antabuse) & Citrated calcium cyanamide

(Carbimide)
Disulfiram – It interferes with the oxidation of acetaldehyde formed during the metabolism
of alcohol. It also inhibits dopamine-b Oxidase & thus interferes with the synthesis of NA.
This causes depletion of catecholamines.
4-Methyl pyrazole (inhibitor of alcohol dehydrogenase) used in treatment of methanol &
ethylene glycol poisoning.

GENERAL ANAESTHETICS
They bring about loss of all Modalities of sensation in particularly pain along with a
reversible loss of consciousness.
Minimum Alveolar concentration: - It is the minimum amount of the anaesthetic in
pulmonary alveoli required to produce immobility in response to a painful stimuli, used in
dose fixation& Capacity of anaesthetic is measured.
Classification:-
A.Inhalational Anaesthetics –
1. Volatile liquids:-Chloroform, Diethyl ether, Trichloroethylene, Halothane, Enflurane
& Isoflurane
2. Gases: - Cyclopropane, Nitrous oxide, chloroform & Cyclopropane
B. Non – volatile (I.v.) Anaesthetics –

1. Inducing agents: - Thiopentone sodium, Propafol, Etomidate
2. Slower acting drugs: - a) Benzodiazepines – Diazepam, Lorazepam&Midazolam
b) Dissociative Anaesthetics: - Ketamine
c) Neurolept Analgesia: - Fentanyl + Droperdiol
(Analgesic) (Butyrophenone)
M.O.A.:- Most of the general anaesthetics acts by blocking synaptic transmission but some
act by blocking excitatory transmission but some act by prolonging the synaptic inhibition (
Potentiaion of GABA-A ) thus depressing all the functional elements of CNS.
Inhalational anaesthetics, Barbiturates & Benzodiazepines act by potentiating the action of
the inhibitory neurotransmitter GABA at GABAA receptor.
Ketamine selectively inhibits the excitatory NMDA type of glutamate receptor.
Stages of Analgesia:-
1. Stage of analgesia – Minor surgical procedures such as incision of Abcess, dental
extraction
Are carried successfully in this stage.
2. Stage of delirium – must be avoided.
3. Stage of surgical anaesthesia – Includes 4 Planes.
4. Stage of respiratory Paralysis –
Pre-Anaesthetic medication: - Term applied to the use of drugs prior to the administration
of an anaesthetic agent, with the objective of making anaesthesia safer & more agreeable to
the patient.
1. Opoid analgesics – Morphine, Pethidine, Buprenorphine to reduce anxiety &
apprehension of the patient.
2. Sedative & Tranquilizers – Benzodiazepines& Barbiturates
3. Anticholinergics – Atropine or Scopalamine
4. Antiemetics – Phenothiazines(Promethazine & trimeprazine), Metoclopramide
5. H2 Blockers – Ranitidine & famotidine to avoid gastric regurgitation & aspiration
pneumonia
6. Neuroleptics – Cpz, triflupromazine
Alphaxolone is a steroidal drug having anaesthetic property.

SEDATIVE & HYPNOTICS
Sedative reduces excitement & is commonly used as an Anxiolytic

Hypnotic produces sleep resembling natural sleep.
CLASSIFICATION:-
1. Barbiturates – Long acting (Phenobarbitone & mephobarbitone)

Short acting (Butobarbitone, Secobarbitone, and Pentobarbitone)
Ultra short acting (Thiopentone, Methohexitone& Hexobarbitone)
2. Benzodiazepines – Anticonvulsant (Diazepam, Clonazepam& Clobazepam)
Antianxiety (Diazepam, oxazepam, lorazepam, alprazolam, Chlordiazepoxide)
Hypnotics (Diazepam, nitrazepam, flurazepam, temazepam, midazolam)
3. Alcohols – chloralhydrate, Ethchlorvynol
4. Aldehydes – Paraldehyde
5. Acetylated carbinols – Ethinamate, Meprobamate
6. Imidazopyridine – zolpidem
7. Cyclopyralone – Zopiclone
8. Oxazolidine Diones – Paramethadione & Trimethadione
9. Miscellaneous – Methaqualone, antihistaminics & scopolamine
M.O.A.:-
Barbiturates – They act primarily at the GABA: BZD receptor – Cl- channel complex &
they potentiate GABAergic inhibition by inducing the opening of the chloride channel.
Benzodiazepines – They act by enhancing presynaptic/postsynaptic inhibition through a

specific BZD receptor, which is an integral part of the GABAA receptor – Cl- channel
complex. The binding site for GABA is located in the b subunit while the a subunit contains
the BZD binding site. The modulatory BZD receptor increases the frequency of cl- channel
opening.
DRUGS AFFECTING GABAA RECEPTOR- CL- CHANNEL COMPLEX ARE
GABAA GABAB BZD site(a site)

Endogenous agonist GABA GABA
Agonist Muscimol Baclofen BZD
Competitive Bicculine Saclofen Flumenazil
antagonist
Inverse agonist b carboline

ANTI – CONVULSANTS
These are the agents used to treat convulsions
Agents that produce convulsions are Bicculine, Pentylene tetrazole, Strychnine& Picrotoxin
CLASSIFICATION:-
1. Hydantoin derivatives – Phenytoin,Methatoin & ethatoin
2. Barbiturates – Phenobarbitone & Primidone
3. Iminostilbines – Carbamazepine
4. Succinimides – Ethosuximide & Methsuximide
5. GABA Transaminase inhibitors – Sodium Valproate, Vigabatrin
6. GABA reuptake inhibitors – Tiagabin
7. GABA Agonists – Gabapentin
8. Benzodiazepines – Diazepam,Clonazepam&Clobazepam
9. Miscellaneous– Lamotrigine,Acetazolamide,Sultiame(Sulphonamide), Amphetamine
1. Hydantoin derivatives:-
M.O.A. – It acts by inhibiting the spread of seizure discharges in the Brain & Shortens the
duration of after discharge. The drug causes dose-dependent block of sodium channels, thus
reducing the neuronal sodium concentration leading to a reduction in Post titanic potentiation
(PTP) & to increase the neuronal Potassium concentration.
AR – Hyperplasia, Hypertropy of gums, Osteomalacia, Hyperosmolar&non-Ketotic Coma.
Uses – Grandmal, Focal cortical epilepsy. Psychomotor seizures & Neuralgia
2. Barbiturates;-
M.O.A. – Potentiates GABAergic inhibition
AR – Vit-K depletion, Megaloblastic Anaemia & osteomalacia
USE: They are used in the treatment of resistant grandmal, cortical seizures.
Primidone is a Deoxy Barbiturate converted in the liver to 2 active metabolites

Phenobarbitone & Phenyl ethyl malonamide.
3. Iminostilbines: - It increases threshold to PTZ & Electroshock convulsions

AR – Peripheral neuritis, Agranulocytosis, Obstructive jaundice, Aplastic anaemia &
Thrombocytosis, Diplopia, Vertiga, Ataxia & Lupus like Syndrome.
Uses – Temporal lobe & Grandmal epilepsy, Trigeminal neuralgia, Diabetes insipidus &
Alternative to Lithium CO3 in Mania.
4. Succinimides: - It acts by suppressing T-Current

AR – Blood dyscrasiasis, SLE, Psychic disturbances & GIT disturbances.
Used in Temporal lobe epilepsy
5. GABA transaminase Inhibitors: - Potentiates Post synaptic GABA activity & decrease
brain levels of EAA.
6. Oxazolidine Diones: - Raises threshold to Seizures

AR – Hemeralopia, Kidney damage Used in Petitmal epilepsy
7. Miscellaneous:-
Lamotrigine – blocks voltage sensitive sodium channel
Acetazolamide – Inhibits CA & acts by increasing CO2 levels in the Brain or by decreasing
sodium there by increasing Seizure threshold.

ANTIPSYCHOTICS
Antipsychotics/ Tranquilizers/ Ataractics are the drugs reduce Apomorphine induced

Sterotype & Amphetamine induced Hyperactivity & also inhibit conditional avoidance
response and cause some Ataxia.
CLASSIFICATION:-
1. Phenothiazine derivatives –
a) Aliphatic side chain: - CPZ, triflupromazine

b) Piperidine side chain: - Thioridazine & Mesoridazine
c) Piperazine side chain: - trifluperazine, Fluphenazine&thioproperazine
2. Butyrophenones – Haloperidol, Trifluperidol, Droperdiol&Penfluridol

3. Rauwolfia Alkaloids – Reserpine
4. Thioxanthines – Chlorprethixene, Thiothixene& Flupenthixol
5. Indole derivatives – Molindone
6. Substituted Benzamides – Sulpiride
7. Atypical neuroleptics – Clozapine (Dibenzodiazepines), Reserpidone
8. Miscellaneous – Oxypertine, Loxapine, Pimozide
M.O.A:-
Most of them act by following 3 ways-
1. Cause Blockade mainly of post synaptic Dopaminergic (D2) receptors & to a small extent
5-HT receptors.
2. Modify functions of Mesolimbic system.
3. Reduce incoming sensory stimuli by acting on the brain stem reticular formation.
All Antipsychotics except clozapine have potent Dopamine (D2) blocking action.
Dopamine acts as an excitatory neurotransmitter at D1 & D5 while Dopamine acts as an
inhibitory neurotransmitter at D2 , D3& D4 receptors.
Clozapine acts by 5-HT2 as well as a1 Blockade.
Reserpidone acts by 5-HT2 as well as D2 Blockade.
AR- Anticholinergic effect, Extrapyrimidal effects, Weight gain
ANTI-ANXIETY AGENTS
Elevated plus Maze test is used to evaluate Anti-anxiety agents.
Class Drugs M.O.A.

Benzodiazepines Diazepam,Alprozolam,Oxazepam, Potentiates GABAergic
Lorazepam,Chlordiazepoxide Inhibition.
Azapirone Buspirone,Gepirone,Ipsapirone Stimulates Presynaptic 5-HT1A
Autoreceptors.
Others Meprobamate,Hydroxyzine Antihistaminic with sedative,
antimuscarinic & Spasmolytic
actions.
b- blockers Propranolol By reducing B.p. tremor &
palpitation.

AFFECTIVE DISORDERS
Refers to pathological change in mood state. The 2 Extremes are Mania & Depression.
Drugs like Antidepressants & Antimanics (Mood stabilizers) are used.
Anti-Depressants:-
A.MAO Inhibitors
1. Non-selective
a) Hydrazines: - Phenelzine, Isocarboxazid& iproniazid Irreversible
B) Non-Hydrazine:- Tranylcypromine
c) Reversible: - Moclobemide
2. Isoenzyme Selective
a) MAO-A Inhibitor: - Clorgiline, Moclobemide
b) MAO-B Inhibitor: - Selelegine (Deprenyl)
B. Tricyclic Antidepressants
1. Nor-Adrenaline & 5-HT reuptake Inhibitors
Imipramine, Amitryptiline, Trimipramine, Doxepin, Clomipramine, Dothiepin & Venlaflexin
2. Nor-Adrenaline reuptake Inhibitors

Nortryptyline, Desipramine, Protryptiline, Amoxapine
3. Selective 5-HT reuptake Inhibitors

Fluoxetine, Fluvoxamine, Paroxetine, sertraline & Alpacrolate
4. Atypical Antidepressants
Trazodone, Bupropion, Mianserin, Tianeptine
M.O.A:-
MAO Inhibitors act by inhibiting MAO (Enzyme responsible for degradation of Catecholamines).
Tricyclic Antidepressants Inhibit active uptake of Biogenic amines NA & 5-HT in to their
respective neurons & thus potentiate them.
ANTIMANICS/ MOOD STABILIZING DRUGS:-
Lithium carbonate – They act by replacing Na+ by Li+ this affects ionic fluxes across Brain
cells or modify the property of cellular membranes.
They decrease the release of NA & dopamine in the Brain with out affecting 5-HT release.
They inhibit action of ADH on distal tubules & causes diabetes insipidus like state.
Alternatives used as Antimanics – Carbamazepine, Sodium valproate.
Hallucinogens: - (Psychomimetics/ Psychedelics/ Psychodysleptics/ Psychotogens)
These drugs alter mood, behavior, thought & perception in a manner similar to that seen in
Psychosis.

Classification:-
1. Indole amines: - LSD, Psilocybin, Harmine, Bufotenine & dimethyltyrptamine
2. Phenyl alkylamines: - Mescaline
3. ArylcycloHexylamines: - Phencyclidine
4. Cannabinoids: - Tetrahydro Cannabinol
Phencyclidine is a Hallucinogen structurally similar to Ketamine.
Psychomotor stimulants: -
Caffeine, Amphetamine & Piperidyl derivatives (Pipradrol & Methyl phenidate).
Used in Narcolepsy, Catoplexy & Attention deficit Hyperactivity disorder (ADHD).
OPIOID ANALGESICS
 The opioid drugs produce their effects by combining with opioid receptors which are
widely distributed in CNS & other tissues.
 Opiods & their Antagonists act at Mu receptors.
 The side effects such as vomiting, Sweating & Hallucinations are due to action of
drugs on subtype of Kappa receptors.
m j k
Endogenous Endomorphin 1&2 Leu/Meth Dynorphin A
agonists b-Endorphin (31a.a) Enkephalein (5a.a)
Exogenous agonists Morphine Morphine Ketocyclazocine
Selective agonists b-Funaltrexamine Norbinaltorphimine
m1-naloxanazine
B-Endorphin is a pain modulator in the CNS derived from Pro-opio-Melanocortin
Opium alkaloids are divided as

1. Phenanthrene group
2. Benzyl isoquinoline – Papaverine, Noscapine
Devoid of analgesic activity, Intracarvenosal injection of papaverine causes penile
errection. Noscapine is a potent releaser of Histamine. & large doses cause Hypotension.
Morphine – Used as sulfate/HCl salt

Produces Analgesia, Euphoria, sedation& Hypnosis.
Causes direct depressant action on Brain stem respiratory centre & reduce the sensitivity of
medullary respiratory centre to increased plasma CO2 concentration. With toxic doses
breathing is entirely maintained by ‘Hypoxic Drive’ mediated through the carotid & aortic
body chemoreceptors & results in ‘Cheyne Stokes Respiration’.
Causes Miosis, Nausea Cough suppression, Stimulates Vagus nuclei, Excites spinal cord &
raises CSF.It also releases ADH.
GIT: - spasms followed by increase in intrabiliary pressure.
T.uses – Powerful analgesic, sedative, Pre-anaesthetic medication, general anaesthetic

Contraindications- In, hypopitutarism, Addison’s disease, Head injuries, impaired kidney &
liver functions.

Codeine – Devoid of respiratory depression, enhances analgesic effect in combination with Aspirin.
Note: - All the 3 types of receptors are antagonized by Opioid antagonists such as Naloxone
& Naltrexone.
The drugs which act as partial agonist-antagonists at the opioid receptors are Nalorphine,
Levallorphan, and Pentazocine&Nalbuphine.
NSAIDS: - Extensively protein bound drugs.

Classification –
1. Salicylates:-
2. p-Aminophenol derivatives: - Phenacetin, Paracetamol, & Acetanilide
3. Pyrazolone derivatives: - Phenyl Butazone
4. Indole & related drugs: - Indomethacin, Sulindac
5. Heterocyclic Aryl acetic acid derivatives: - Diclofenac, Tolmetin&Keterolac
6. Propionic acid derivatives: - Ibuprofen, fenoprofen, Naproxen, Ketoprofen
7. Fenamates: - Flufenamic acid, & Mefenamic acid
8. Oxicams: - piroxicam
9. Sulfonanilides: - Nimesulide
M.O.A:- Cox-1 is present in Stomach, Kidney& Blood vessels. Where as Cox-2 in

inflammatory cells& activated leucocytes.NSAIDS act by inhibiting COX, responsible for the
conversion of arachidonic acid to Prostaglandins.
Salicylates: - prevent the release of Histamine, Lowers ESR (erythrocyte sedimentation rate)
Inhibits platelet aggregation. In small doses elevate plasma urate levels while in large doses
causes uricosuria. Induces release of adrenaline from adrenal medulla.
In case of salicylate poisoning supplement of Vit-k is given along with other formalities.
Trusses – Antirheumatic,
Antiplatelet, Analgesic, Antipyretic, Counterirritant, Keratolytic, fungistatic, Antiseptic,

Antiinflammatory.
Selective Cox-2 inhibitors: - Nimesulide, celecoxib, rofecoxib, meloxicam
GASTROINTESTINAL DRUGS
Achlorhydria: - Absence in production of HCL leading to improper digestion. It can be

treated by 10ml of 10% HCL diluted 100ml H20.
Hypochlorhydria: - decreased production of HCL.
Sialorrhoea: - increased salivary production
ORS: - Oral rehydration solution. Glucose – 20g, Nacl – 3.5g, Kcl – 1.5g, NaHCo3 (2.5g) or
tri sodium citrate (2.9g) – distilled water (1-L).
Mumps: - infectious, inflammatory swelling of paratoid & other salivary glands.
Hydragogue: - Drug which produces watery stools.
Dyspepsia: - disorder of abdomen or chest with flatulence, nausea etc.

Achyliagestrica: - Absence of HCL.
Bitters: - They increase appetite by promoting gastric acid secretion. E.g.:- gentian, chirata,
picrorrhiza Alcohol & 2 other Antihistaminics (cyproheptidine, Buclizine) also acts as
appetite stimulants.
Anorexia nervosa: - Chronic disease characterized by loss of appetite, weight loss,

physiological & psychological alterations.
Digestants: - which aid in digestion in GIT.

E.g.:- Diastase & Taka diastase – Amylolytic,
Papain – Proteolytic,
Pancreatin – Amylolytic & Proteolytic,
Bromelain – Amylolytic, lipolytic & proteolytic,
Lipase – Lipolytic.
Carminatives: - expels gas with relaxation of sphincters. E.g.:- Volatile oils & Spices.
Gall stone dissolving drugs: - Ursodiol & chenodiol

Bile salts are essential for digestion of cholesterol, when the amount of cholesterol in body
increases, they form gall stones, and thereby bile acids are used for dissolving gall stones.
Bile acids: - Chenodiol (cholic acid) & Ursodiol (taurocholic acid) both inhibit absorption
of cholesterol.
Bile salts: - Sodium glycocholate & sodium taurocholate.
Bile pigments: - Bilurubin, Biliverdin, Stercobilin & Stercobilinogen.
Peptic ulcer: - due to imbalance between aggressive factors (acid, pepsin & H-pylori) &
defensive factors (gastric mucus & bicarbonate secretions, PG’S innate resistance of the
mucosal cells).
METHODS OF TREATING PEPTIC ULCER:-

1. By reducing gastric acid secretion :-
Class Drugs M.O.A A.R.

H2 Blockers Cimetidine Blacks H2 receptors Cimetidine causes
ranitidine gynacomastia &
Roxatidine inhibiting cytp450
famotidine
Proton pump Omeprazole H+K+ inhibits Atpase Nausea headache loose
inhibitors Lansoprazole present in parietal cells stools
Pantoprazole
Anticholinergies pirenzepine Decreases cholinergic Intolerable side effects
Propantheline secretions
PG Analogues Misoprostol Inhibit acid secretion & Contraindicated in
Rioprostil Enprostil promote mucus & pregnancy
bicarbonate secretion
Inhibit gastrin production

Cimetidine Produces Anti Androgen Effect by displacing the Dihydro testosterone from the
cytoplasmic receptors, Increases plasma prolactin level & inhibits the metabolism of Estrogens.
2. Neutralization of gastric acid: - Systemic antacids – NaHco3, Non Systemic antacids –

Al (oH)3, Mg (oH)2.
MAGALDRATE – Hydrated complex of Hydroxy Magnesium Aluminate.
Acid neutralizing capacity: - Number of milli equivalents of 1N HCL that is brought to PH

3.5 in 15 mins by unit dose of the preparation.
3. Ulcer protectives :-
Sucralfate – Aluminium salt of sulfated sucrose at pH – 4 it polymerizes to form a gel & gets
deposited on the wall of stomach.
Colloidal Bismuth Sub citrate – increases Pg synthesis. They also destroy H.Pylori
4. Ulcer healing drugs: - Carbenoxolone sodium, Deglycyrrhizinised licorice.
5. Anti.H.Pylori:- Metronidazole, Tinidazole.
Combination therapy = Clarithromycin + Amoxycillin + Omeprazole.
Polymethyl siloxane: - Collapes froth, improves dispersion of Antacid, reduces gastro

esophageal reflux & thus relieves Heart Burn.
Drug contraindicated in peptic ulcer: Caffeine, reserpine, Aminophylline, glucocorticoids, NSAIDS.
EMETICS
Emetine, Apomorphine, Hypertonic saline solution, mustard (sinigrin)

Anti emetics:-
Anticholinergies – Hyoscine, Dicyclomine
H1 Antihistaminics – Promethazine, Diphenhydramine, Cyclizine, Cinnarazine
Neuroleptics – CPZ, Haloperidol, Prochlorperazine
Prokinetic drugs – Metoclopramide, Domperidone,
5HT3 antagonists – Ondansetron, granisetron
DRUGS ACTING ON RESPIRATORY SYSTEM
Respiratory quotient: - ratio of oxygen consumed to the carbondioxide evolved.
1. Pharyngeal demulcents: - sooth the throat directly as well as by promoting salivation

E.g.:- Lozenges, Glycerine, Liquorice.
2. Expectorants (mucokinetics):-
Directly acting:- eucalyptus & lemon oil, Guainaphenesin, Vasaka.
3. Reflexly acting: - saline expectorants (NH4cl, KI, K-citrate)
4. Antitussives :-
 Opioids – Codeine, morphine.
 Non-Opioids – Noscapine, Dextrometrorphan, Clophedianol, Carbetopentane
& Oxeladin

5. Antihistaminics – Chlorpheniramine, diphenhydramine,Promethazine

6. Mucolytic agents: - decreases viscosity of sputum. E.g.:- Acetylcysteine, bromohexine,
Ambroxol pancreatic dornase.
7. Nasal decongestants: - ephedrine, phenyl ephrine Naphazoline & Oxymetazoline.
Bronchodilators:-
1. Sympathominetics – ephedrine, adrenaline, salmeterol

2. Methyl xanthines – Theophylline
3. Anticholinergics – Ipratropium bromide Atropine methonitrate.
 Cromolyn sodium is a prophylactic agent that stabilizes most cells in asthma.

 Prednisolone is life saving in serve status asthamaticus & inhibitor of
phospholipase A2.
 Ipratropium is bronchodilator in chronic obstructive pulmonary disease with
least cardiac effects.
 Ketotifen – Orally active, Prophylactic agent in Bronchial Asthma & Allergic
disorders.
 Inhalational Steroids – Beclomethasone, dipropionate& Budesonide.
Catarrh: - state of irritation of mucous membranes associated with a copious secretion of mucus.
DRUGS ACTING ON C.V.S
Cardiac glycosides: - These glycosides have cardiac inotropic activity. They increase
myocardial contractility & output without proportionate increase in O2 consumption. E.g.:-
Digitoxin, Digoxin, Lanatoside – C, quabain
M.O.A:- Cardiac glycosides selectively bind to membrane bound Na+/K+ ATPase pump.
This results in accumulation of Na+ intracellularly and this indirectly results in intracellular
accumulation of Ca2+, this leads to increased myocardial contractility.
Therapeutic index = 1.5 – 3.0 (Digitalis)
Properties Digitoxin Digoxin Lanatoride – c Quabain

Oral absorption Excellent Good Low Low
PPB 95 % 25% 25% Poor
2plasma t1/2 7 days 2 days 2 days 1 day
Potency Less Intermediate Intermediate High
Elimination Hepatic Renal Renal Renal
Uses: - CCF, cardiac arrhytmias such as atrial flutter & atrial fibrillation.
Cardiac arrhythmias: - refers to changes in Cardiac rhythm.

Antiarrhythmic drugs:-
I – Sodium channel Blockers
Class M.O.A Examples

IA Prolongs repolarisation Quinidine, Procainamide Disopyramide.
IB Shortens repolarisation Lidocaine, Phenytoin tocainide.
IC Slows conduction Encainide, Flecainide Propafenone.
Affinity towards Na+channel = class IC > class IA > class IB
II – B Blockers E.g.:- propranalol

M.O.A:- slows conduction & suppresses automaticity.
III – K+ channel blocker E.g.:- Amiadarone, Bretylium, Sotalol

M.O.A:- prolongs refraction
IV – ca2+ channel blocker E.g.:- verpamil, Diltiazem blocks inward ca2+ current.
V – Digitalis.
Cardiac arrhythmic disorders First line drugs/ Drug of choise

PSVT Adenosine/Verpamil
Av Block Atropine
Atrial extra systole Quinidine
Atrial flutter/Atrial fibrillation Verapamil
Ventricular extra systole/ventricular tachycardia Lidocaine
Wolf Parkinson white syndrome Amiodarone/Flecainide
ANTI-ANGINAL DRUGS
Used to treat Angina pectoris
Angina pectoris: - where the O2 demand of the myocardium exceeds that of the supply.
Stable angina: - generally caused due to stress
Unstable angina: - due to occlusion of coronary arteries by plague.
Variant / Prinzmetal angina: - It occurs at rest due to recurrent localized coronary

vasospasms.

Classification:-
A. Organic nitrates: - i) short acting: - glyceryl trinitrate.

ii) Long acting: - ISDN, ISMN.
B. B – Blockers: - Propranalol.
C. Ca2+ channel Blockers: - Verapamil, Nifedepine, Diltiazem.
D. K+ channel openers: - Nicorandil, minoxidil.
E. Antiplatelet drugs: - Aspirin, Dipyridamole.
F. Cytoprotectives: - Trimetazidine.
Nitric oxide (EDRF) is synthesized in body from L-arginine as follows –
 L-arginine N.O.synthetase N.O. +citrulline
 Organic nitrates are rapidly denitrated in the smooth muscle cell to release the
reactive free radical N.O. that activates guanyl cyclase, which causes the formation of
CGMP from GTP. CGMP causes desphorphorylation of MLCK through CGMP
dependent proteinkinase. Reduced availability of phosphorylated MLCK interferes
with activation of myosin & it fails to interact with actin & this leads to relaxation.
 Nitrates are also used to treat cyanide poisoning as nitrates form methemoglobin with
Hb. So that cyanide cannot act on methemoglobin.
Potassium channel openers: - since intracellular concn of K+ is much higher compared to

extra cellular region, K+ channel opening results in outflow of K+ ions & hyperpolarisation.
Uses: - Angina pectoris, Hypertension, CHF.
AR: - Hirsutism.
Desferrioxamine: - A high affinity iron cheater used as a protective in ischemic myocardial

injury through its anti-free radical effect.
Vasodilators: - They are used in Hypertension, myocardial infarction, angina attacks etc.
1) Arteriolar vasodilators: - Hydralazine, minoxidil, nifedepine, diazoxide, nicorandil.
2) Venous vasodilators: - Glyceryl trinitrate, ISDN.
3) Mixed vasodilators: - Losartan, sodium nitroprusside, prazosin.
Selective phosphodiesterase inhibitor: - Amrinone is an inotropic agent. It is a bipyridine

derivative & inhibits PDE – III.
Milrinone (derivative of Amrinone) & 10 times more potent than Amrinone.
Drotavarin inhibits PDE – V.
Non-selective PD inhibitor: - Cilastazole & Theophylline dithiothreol is used to stop the

action of nitrates by removing nitrate groups attached to ‘SH’.

ANTIHYPERTENSIVE DRUGS:
 These are drugs used to lower BP in Hypertension.
 Blood pressure is the product of cardiac output and peripheral resistance.
 Cardiac output is the amount of blood pumped by the heart in one minute and is
therefore the product of stroke volume and the heart rate. Stroke volume refers to the
volume of blood pumped during each contraction.
 B.P = C.O * T.P.R, C.O = stroke volume * Heart rate.
 Thus it can be observed that most of the antihypertensive drugs act by either
decreasing peripheral resistance or by decreasing cardiac output.
MECHANISM OF
CLASS DRUGS ADVERSE EFFECTS
ACTION MOA
Enalpril,
(prodrug)
They inhibit ACE
Lisinorpril,
essential for the
(prodrug)
conversion of AT-I to AT- Dry cough, angioedema,
Ramipril
ACE inhibitor II, Urticaria and taste
(prodrug)
disturbance.
Captopril
which is a potent
(nonprodrug)
vasoconstrictor
Saralasin
Losartan,
irbesatran
valsartan,
Angiotensin They antagonize the
telmisatran
receptor action of AT-II at the Usually well tolerated.
candesartan
antagonist angiotensin receptor.
(Peptide
analogue).
Verapamil,
Calcium They lower b.p by Agents such as
nifedepine,
channel decreasing peripheral diltiazem/verapamil have
amlodipine
blockers resistance negative inotropic action.
They induce diuresis that Thiazide diuretics cause

Chlorthiazide,
reduces plasma volume hypokalemia and also
Diuretics furosemide,
which in turn reduces C.O hyperglycemia in
spironolactone.
leading to a drop in b.p. diabetics.
They decrease sinus Myocardial insufficiency
rhythm, which leads to a Bradycardia Asthma
Metoprolol,
 Blockers decrease in heart rate, Heart block.
propranolol
which leads to a drop in Insulin dependent
b.p. diabetics.

They block the action of

adrenaline at the a
 Adrenergic Prazosin, Impotence postural hypo
receptor present in blood
blockers terazosin tension
vessels thereby leading to
vasodilatation
The-nor methyl adrenaline
formed from methyldopa
Methyldopa
Central acts as false neuro Sedation, lethargy and
clonidine
sympatholytics transmitter on a2 and reduced mental capacity.
(h2 agonist)
decreases efferent
sympathetic activity.
Displaces N.T. from
Neurotransmitt Guanethedine
synapse increases
er depletors reserpine
N.T.metabolism
Hydralazine on prolonged
Vasodilatation leads to a use causes SLE
Hydralazine, decrease in peripheral (Systematic lupus
Vasodilators
minoxidil resistance, which in turn erythrematosus),
leads to fall in b.p. hirsustism, peripheral
pooling of blood.
Ethacyranic acid is contraindicated in Angina in Asthma B2 blockers is avoided.
ANTIHYPERLIPIDEMIC DRUGS:
These drugs lower the levels of lipoproteins and lipids in blood. The different types of
hyperlipoproteinemia are:
Elevated plasma
Type Disorder Elevated plasma lipids
lipoprotein
Cholesterol &
I Lipoprotein lipase deficiency Chylomicron
triglycerides
Familial
IIa LDL Cholesterol
hypercholesterolemia
Polygenic Cholesterol (moderate
IIb LDL (B-lipoprotein)
hypercholesterolemia increase)
Familial IDL, Cholesterol &
III
Dysbetalipoproteinemia chylomicron remnants triglycerides
VLDL
IV Hypertriglycereridemia Triglycerides
(pre-B lipoprotein)
Cholesterol &
V Hyperlipedemia VLDL, LDL
triglycerides

THE CLASSIFICATION OF HYPOLIPEDEMIC DRUG IS AS FOLLOWS:
Class Drugs Mechanism of action Adverse effects

They inhibit the enzyme HMG-
HMG-CoA Lovastatin, CoA Reductase essential for the Headache, rise in
Reductase atorvastatin, conversion of HMG-CoA to serum transaminase,
inhibitors simvastatin mevalonate and thus inhibit rise in CPK levels.
synthesis of cholesterol.
These are ion exchange resins that
bind bile acids in the intestine Unpalatable and may
Bile acid Cholestyramine, inhibit their enterohepatic cause nausea,
sequestrants colestipol circulation. Cholesterol is absorbed flatulence, heartburn,
with the help of bile acids and in constipation.
their absence, it is excreted.
Increased appetite
They activate lipoprotein lipase
Clofibrate, and weight gain,
Fibric acid which is essential for the
Gemfibrozil, myalgia and
derivatives degradation VLDL resulting in
fenofibrate increased incidence
lowering of TG’s.
of gallstones.
Neomycin lowers LDL-CH by Neomycin may
Neomycin,
complexing with bile acids in the however damage
Others gugulipid
intestine. Guggul lipid probucol intestinal mucosa.
probucol
acts as Antioxidant Loose stools.
 Comniphora molmol – myrh (antiseptic),

 Comniphora mukul – guggul (antihyperlipedemic).
 Dromotropic – Drug affects conductivity of impulses in neuronal cells.
HORMONES
 They are mediator molecules act as chemical messengers.

 They are released in one part of the body & regulates activity of cells in other ports of Body.
 Hormones are secreted by endocrine or ductless glands.
 Most hormones enter interstitial fluid & then the Bloodstream.
M.O.A:- Hormones like, neurotransmitters, influence their target cells by chemically binding
to specific protein or glycoprotein receptors.
SITE OF ACTION:-
At cell membrane receptors – E.g.:- Adrenaline, glucagons, FSH, LH, TSH, ACTH
calcitonin, vasopressin, oxytocin, insulin etc.
At cytoplasmic receptors – E.g.:- steroidal Hormones.
At nuclear receptors – Thyroid Hormones.

Down regulation: - when hormone is present in excess, the no. of target cells receptors
decreases. This makes target cells less responsive to the hormone.
Up regulation:- when there is a deficiency in hormone is the no. of receptors may increase.
This makes target cells more sensitive to hormone
Classification of hormones: - The endocrine glands include pituitary, Thyroid, Parathyroid,

Adrenal and pineal glands.
Water soluble hormones: - protein eicosanoid hormones.
Lipid soluble hormones: - Steroid, Thyroid & gaseous hormone (Nitric oxide).
Placental hormones: - Chronic gonadotropin – Prolactin, Estrogens – Progesterone,
Placental lactogen – Chorionic thyrotropin.
Hormones of the Anterior & Posterior Pituitary:-
Inhibiting
Releasing Hormone hormone
Hormone Secreted by
(stimulates secretion) (suppresses
secretion)
Growth harmone-
Human growth hormone Growth hormone-releasing inhibiting
(hGH) or somatotropin Somatotrophs hormone (GHRH) or hormone (GHIH)
(191aminoacid) somatocrinin (44A.A) or somatostain
(14AA)
Growth hormone-
Thyroid-stimulating
Thyrotropin releasing inhibiting
hormone (TSH) or Thyrotrophs
hormone(tripeptide) hormone
thyrotropin
somatostatin
Follicle-stimulating Gonadotrophic releasing
Gonadotrophs ---------
harmone (FSH) harmone(decapeptide)
Luteinizing harmone Gonadotrophic releasing
Gonadotrophs ---------
(LH) harmone
Prolactin
Prolactin (PRL)
Lactotrophs Prolactin releasing harmone inhibiting harmone
(198aminoacid)
or dopamine
Adrenocorticotropic
Corticotropin releasing
harmone (ACTH) or Corticotrophs ----------
harmone(41aminoacids)
corticotrophin
Mealanocyte-stimulating Corticotropin releasing

Corticotrophs Dopamine
harmone (191aminoacid) harmone
 Leuprolide is a synthetic non-peptide of GTRH.

 Dropamine antagonist not given in lactating women because it inhibits prolactin.
 Enuresis – Bed wetting (Desmopressin)
 Melatonin – (responsible for normal sleep)
 Posterior pituitary or neurohypophysis does not synthesize harmones; it stores and
releases two harmones oxytocin and antidiuretic harmones (vasopressin).

HORMONE PRINCIPAL ACTIONS

Stimulates liver, muscle, cartilage, bone, and other tissues to
Human growth harmone synthesize and secrete insulin like growth factors. (IGF’s);
(hGH) or somatotropin IGFs promote growth of body cells, protein synthesis, tissue
repair, lipolysis, and elevation of blood glucose concentration.
Thyroid-stimulating
Stimulates synthesis and secretion of thyroid harmones by
harmone (TSH) or
thyroid gland
thyrotropin
In females, initiates development of oocytes and induces
Follicle-stimulating
ovarian secretion of estrogens. In males stimulates testes to
harmone (FSH)
produce sperm.
In females, stimulates secretion of estrogens and progesterone,
ovulation and formulation of corpus luteum. In males,
Luteinizing harmone (LH)
stimulates interstitial cells in testes to develop and produce
testosterone.
Prolactin (PRL) more
Together with other harmones, promotes milk secretion by the
active in presence of
mammary glands.
oxytocin
Adrenocorticotropic
Stimulates secretion of glucocorticoids (mainly coritsol) by
harmone (ACTH) or
adrenal cortex.
corticotrophin
Melanocyte-stimulating Exact role in humans is unknown but may influence brain
harmone activity, when present in excess, can cause darkening of skin.
Stimulates contraction of smooth muscle cells of uterus during
Oxytocin (OT) childbirth; stimulates contraction of myoepithelial cells in
mammary glands to cause milk ejection.
Conserves body water by decreasing urine volume; decreases
Antidiuretic harmone
water loss through perspiration; raises blood pressure by
(ADH) or vasopressin
constricting arterioles.
Pitutary harmone derivates:-
ANALOGUE USES
Bromocriptine Prolactin inhibitor Cancer therapy
Desmopressin ADH Diabetes insipidus
Gasrelin, coryntropin, Leuprolide ACTH Infantile spasms
Menotropins, urofollitin FSH, LH Infertility

Naferelin GNRH Cancer, Infertility
Ocreolide Somatostatin Inhibits glandular

GONADAL HARMONES USES

Tamoxifen Breast cancer
Diethylstilbesterol After contraception
Estrogen & progesterone Oral contraception
Norgesterol & medroxyprogesterone chronic contraception
Mifepristone Abortifacient
Oxandralone Anabolic
THYROID GLAND
The follicular cells produce two harmones; thyroxine (tetraiodothyronine) and tri-
iodothyronine, which are known as thyroid harmones.
Synthesis and secretion of T3 and T4 occurs as follows:
a. Iodine trapping: Follicular cells trap iodine ions by an active transport

mechanism.
b. Synthesis of thyroglobulin: While the follicular cells are trapping iodide
ions, they are also producing thyroglobulin (TGB).
c. Oxidation of iodide: Iodine ions are oxidized by peroxidase to form iodine
(I2).
d. Iodination of tyrosine: as iodine molecules form, they react with tyrosines
that are part of thyroglobulin molecules. Binding of one iodine atom with
tyrosine yields mono-iodotyrosine (T1), while two iodine atoms yields di-
iodotyrosine (T2),
e. Coupling of T1 and T2: two T2 molecules combine to form T4 while one T1
and one T2 combine to form T3 in the presence of peroxidase.
Calcitonin: - It is a harmone produced by the parafollicular cells of the thyroid gland. It

decreases the level of calcium in blood by inhibiting the action of osteoclasts, the cells that
break down bone matrix.
Parathormone: - It is secreted by the parathyroid glands and it increases blood calcium and
magnesium levels, while it decreases phosphate levels.
The harmones produced by the adrenal cortex are of three types:

a. Mineral corticoids : Aldosterone
b. Glucocorticoids: Cortisol, Coorticosterone & Cortisone.
c. Androgens: Dehydroepidandrosterone.
The harmones produced by the chromaffin cell of the adrenal medulla are Epinephrine and
nor epinephrine.

The four types of pancreatic islets that produce harmones are:-

1. A cells secrete glucagons.
2. B cells secrete insulin.
3. D cells secrete somatostatin.
4. F cells secrete pancreatic polypeptide.
Hormone Control of secretion Principal actions

Thyroid harmone Secretion is increased by Increase basal metabolic rate,
thyrotopin-releasing harmone stimulate synthesis of proteins, and
and high thyroid iodine levels increase use of glucose.
suppresses secretion.
Calcitonin High blood calcium levels Lowers blood levels of ionic calcium
stimulates secretion, low levels and phosphate.
suppresses secretion.
Parathyroid Low blood calcium levels Increases blood calcium and
hormone stimulate secretion; High blood magnesium levels and decreases
calcium levels inhibit secretion. phosphate levels.
Mineral corticoids Increased blood K+ level and Increases blood levels of Na+ and
angiotensin II stimulates water and decrease blood level of K+.
secretion.
Glucocorticoids ACTH stimulates release. Increase protein breakdown stimulate
gluconeogenesis.
Androgens ACTH stimulates release. Assist in early growth of axillary and
public hair.
Epinephrine and Sympathetic preganglionic Produce effects that enhance those of
Nor epinephrine neurons release acetylcholine, the sympathetic division of the
which stimulates secretion. automatic nervous system during
stress.
Glucagon Decreased blood level of Raises blood glucose level by
glucose, exercise and mainly accelerating breakdown of glycogen
protein meals stimulate into glucose in liver.
secretion.
Insulin Increased blood level of glucose, Lowers blood glucose level by
acetylcholine, arginine and accelerating transport of glucose into
leucine, glucagon, GIP, hGH, cells, converting glucose into
and ACTH stimulate secretion. glycogen and stimulates protein
synthesis.
Somatostatin Pancreatic polypeptide inhibits Inhibits secretion of insulin and
secretion. glucagon and slows absorption of
nutrients from the gastrointestinal
tract.
Pancreatic Meals containing protein, Inhibits somatostatin secretion,
polypeptide fasting, exercise, and acute gallbladder contraction, and secretion
hypoglycemia stimulate of pancreatic digestive enzyme.
secretion.

Hormones affecting calcium homeostasis:-

 Calciferol (25 Hydroxy Vit-D3)
 Calcitrol (1, 25 dihydroxy Vit-D3)
 Cholecalciferol (Vit-D3)
 Secalcifediol (24, 25 dihydroxy vitD3)
 Ergocalciferol (VitD2)
 Androgens: - Testosterone, Oxandrolone, Stanozolol.
 Antiandrogens: - Finasteride (synthetic inhibitors).
 Antiprogestins: - Mifepristone.
USEFUL TIPS
 WELCOME TO PHARMAROCKS
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PHARMACOLOGY
 IT COVER GENERAL PHARMACOLOGY, ANS, CNS AND CVS
 REVISE THIS DAILY FOR THE PROPER PREPARATION
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UNDER THIS
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YOUR SEMESTER EXAMS U CAN PREPARE FROM THIS.
 IF POSSIBLE TAKE THE PRINT OUT THIS AND REVISE
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PHARMACOLOGY

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 PHARMAROCLOGY MASTER GPAT NOTES CHEMOTHERAPY
CHEMOTHERAPY MASTER GPAT NOTES

It deals with the use of chemical agent to arrest the progress of infectious diseases by destroying infective parasites or microbes without
damaging the host tissues.
M.O.A:-
1. INHIBITING PROTEIN SYNTHESIS BY BINDING TO RIBOSOMAL SUBUNIT & DESTROYING THE BACTERIAL CELL.
E.g.:- Gentamycin & streptomycin.
2. REVERSIBLE INHIBITION OF PROTEIN SYNTHESIS BY ACTION ON RIBOSOME.

E.g.:- Broad spectrum Antibiotics.
3. BY DETERGENT ACTION (LEAKAGE OF CELL CONSTITUENTS)

A. Direct cell membrane. E.g.:- Colistin, Polymyxin
B. Drug binding to cell wall sterols. E.g.:- Nystatin, Amphotercin.
4. INHIBITION OF CELL WALL SYNTHESIS: -

E.g.:- Penicillins, Cephalosporins, sulphonamides.
5. DRUGS AFFECTING NUCLEICACID METABOLISM:-

A. Inhibition of DNA dependent RNA polymerase. E.g.:- Refampicin.
B. Inhibition of DNA supercoiling & DNA synthesis. E.g.:- Quinolones & Fluoroquinolones.
PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com WEBSITE:http;//pharmarocks.webnode.in/ 1

DRUG RESISTANCE:-
1. Natural: - Organisms do not have target sit for drugs to act. E.g.:- Antifungals in Bacterial infections.
2. Acquired: - Organisms are exposed to the drug in such a manner that it develops resistance.
Cross resistance: -
Development of resistance to one substance may also show resistance to another substance to which the organism has not been exposed.
E.g.:- resistance between Sulphonamides, resistance between Tetracycline’s, resistance between Tetracycline’s & Chloramphenicol.
There is no cross resistance between Animoglycosides.
Super infection/Supra infection: -

 It is due to the use of Broad spectrum antibiotics.
 There is no. of microorganisms inhabiting GIT & these organisms constitute the microbial flora. They are called as “commensals” under
normal conditions; these organisms compete with another for nutrients. & therefore they are unable to proliferate rapidly.
 When a Broad spectrum antibiotic such as chloramphenical / tetracycline is administered, it might kill most of the microbial flora barring
a few organisms. Now these few microbes are free to proliferate rapidly in the absence of competition & they multiply, spread all over
the body & cause infections called super infections.
Antimicrobial agent: - An agent which kills M.O. or suppresses their growth. The susceptibility of AMA is determined by
1. Radiometric method
2. Resistance ratio method (Traditional).
Sulfonamides & Sulfones
These are derived from prontosil red (dye) & are effective against pyogenic Bacterial Infections.

CLASSIFICATION:-
1. Short acting: - Sulfadiazine, Sulfisoxazole.
2. Intermediate: - Sulfamethoxazole.
3. Long acting: - Sulfadoxine, Sulfamethopyrazine.
4. In intestinal infections: - Sulfasalazine.
5. In Burn therapy: - Silver sulfadiazine, mafenide.
6. In ophthalmic infection: - Sulfacetamide.
M.O.A:-
Guanosine…………> PABA _______> Dihydropteroic acid

Several steps (-) Sulfonamides (-) Trimethoprim <……………___________Dihydrofolic acid folate reductase folic acid
DIHYDRO FOLATE REDUCTASE

 Tetrahydrofolic acid ------------N5, N10 methylene FAH4
 N5formylFaH4 -------- N10 formyl FAH4
 N5formylFAH4, N5N10 methylene FAH4, N10formyl FAH4 is very essential for several Biosynthetic pathways in humans & Bacteria.
 The growth and cell division in bacteria can be stopped if any drug blocks Biosynthesis of folate co-enzymes.
 Folate co-enzymes are biosynthesized from dietary folic acid in humans & other animals.
 Sulfonamides act as competitive inhibitors for the incorporation of PABA to form Dihydropteroic acid.
 Trimethoprim is an inhibitor of dihydrofolate reductase required for the conversion of dihydrofolic acid in to tetrahydrofolic acid in
bacteria.

Mechanism of resistance: - It may be due to

1. Increased production of PABA by resistant bacteria
2. Decrease the affinity of folate synthetase enzyme for sulfonamides.
3. Adopts an alternative pathway in folate metabolism. E.g.:- gonococci, pneumococci, E.coli, S.aureus etc
Cotrimoxazole: - fixed dose combination of trimethoprim and sulfamethoxazole in a ratio of (1:5). As this inhibits 2 different steps in pathway,
the development of resistance is reduced.
Adverse reactions:-
1. Stevens Johnson’s syndrome
2. Hemolytic anemia
3. Kernicterus (neonatal Hyperbilirubinemia)
4. Skinrash, Urticaria
5. Crystalluria is due to crystals of sulfanilamide, This can be presented by
i) Alkalanizing the urine
ii) By increasing the urine flow
iii) By reducing PKa of drug.
Metabolism: - It occurs by acetylation at N4 they are excreted as mixtures of unmetabolised drugs, N4 acetates & glucouronides.
Sulfones: - less active than sulfonamides
M.O.A:- similar to sulfonamides. E.g.:- Dapsone

QUINOLONES
E.g.:- Nalidixic acid

Fluoroquinolones: - These are more potent than quinolones.
First generation: Norfloxacin, Ofloxacin, Ciprofloxacin, Perfloxacin.
Second generation: Sparfloxacin, Lomefloxacin.
M.O.A:- They inhibit Bacterial DNA gyrase (An enzyme responsible for introducing negative supercoiling in to circular duplex DNA.)
Negative super coiling relieves the tortional stress of unwinding helical DNA & thereby allows transcription & replication to occur. Humans
have Topoisamerase II in place of gyrase & this accounts for the low toxicity of FQ’s to the host cells.
Resistance: - Due to chromosomal mutation producing a DNA gyrase with reduced affinity for FQ's.
AR: - Hypersensitivity reactions, Hemolytic anemia GI disturbances.
Uses: - Typhoid, soft tissue infection, UTI.
B Lactam Antibiotics
E.g.:- Pencillins & Cephalosporins
M.O.A:- microorganism synthesize two pentapeptides –

1. UDP-N-acetyl muramic acid (NAMA)
2. UDP-N-acetyl glucosamine (NAGA)

These peptidoglycon residues are linked together in forming long strands & the UDP is split off. The final step is cleavage of the terminal D-
Alanine by ‘transpeptidase’. The energy released is utilized for establishment of crosslinkages between peptide chains of the neighbouring
strands.
Beta lactam Antibiotics inhibit the enzyme ‘transpeptidase’ so that crosslinking does not take place. These enzymes constitute the pencillin
binding proteins which are located in the bacterial cell membrane. When Bacteria divide in presence of a B-lactam antibiotic cell wall deficient
forms are produced & these forms burst resulting in cell lysis.
Blood, pus & tissues fluids do not interfere with the antibacterial action of B-lactam Antibiotics.


CLASSIFICATION OF PENICILLIN’S:-
 Natural: - Penicillin-G, procaine penicillinG
 Acid resistant: - Penicillin V (phenoxymethyl penicillin)
 Broad spectrum: - Ampicillin, Amoxicillin, Piperacillin Methicillin
 B lactamase inhibitors: - clavulonic acid, sulbactam
 Monobactams: - Aztreonam
 Carbapenems: - Imipenam, Thienamycin
BACTERIAL RESISTANCE: -
Gram positive organisms develop resistance by producing B-lactamases. (Opens B lactam ring & inactivates) In methicillin resistant S.aureus the
penicillin Binding proteins has been mutated. So that it does not binds methicillin efficiently.
AR: - penicillin allergy due to formation of Antigenic penicilloyl proteins.
Jarisch-Herxhemier reaction is Syphilis patient.
Degradation of penicillin can be controlled by adjusting the PH of aq-solutions between 6.0 – 6.8.
USES: -
Gonorrhea, Syphilis, Diphtheria & coccal infections.
Augmentin = Clavulanic acid + Amoxicillin
Unasyn = Sulbactam + Ampicillin

CLASSIFICATION OF CEPHALASPORINS:-
Cephalosporin = B lactam ring + dihydrothiazine ring
Penicillin = B lactam ring + thiazolidine ring.
I II III IV
Oral Cephalexin Axetal Cefaclor Cefuroxime Cefixime Cefpodoxime ---
Parentral Cephadroxil Cefomandole Cefonacid Cefotoxime Ceftriaxone Cefepime
Antipseudomonal Cephalosporins: -
Cefoperazone, Moxalactam, Cefotaxime, Ceftizoxime & Ceftriaxone.
Disulfiram effect: -
Cefomandole, cefoperazone, cefometazone, cefotetan & moxolactam due to tetrazole group produce Disulfiram effect when taken with alcohol.
Aztreonam is used to treat hospital acquired infections (Nosocomical infections).
Tetracyclines, Chloramphenicol, Aminoglycoside and Macrolide antibiotics

In order to understand the mechanism of the above antibiotics it is essential to understand the process of protein synthesis:
 On a specific signal from the cytoplasm, the DNA in the nucleus unwinds itself with the help of the enzyme DNA gyrate or
topoisomerase (humans).

 One of the strands of the DNA acts a template for the synthesis of a complimentary strand of mRNA in the presence of RNA
polymerase. The synthesis of mRNA from DNA is called transcription.
 The mRNA which now contains the code for protein synthesis comes out of the nucleus and attaches itself to the 30’s ribosomal subunit.
 This is followed by the attachment of the 50’s ribosomal subunit to the mRNA-ribosomal complex.
 There are two sites present on the 50’s ribosomal subunit, the acceptor site and the peptidyl site.
 Protein synthesis does not begin until the mRNA has the initiator codon AUG (codes for formylmethionine) on it.
 Once the mRNA exposes the initiator codon AUG, a specific tRNA carrying the amino acid formylmethionine will arrive at the
acceptor site of 50’s subunit.
 The tRNA carrying the amino acid is now transferred to the peptidyl site where the tRNA dissociates leaving the amino acid at
the peptidyl site.
 The ribosome now moves along the mRNA to expose the next coon.
 Depending upon the codon the corresponding amino acid is brought to the acceptor site by a specific tRNA.
 The tRNA carrying the amino acid is now transferred to the peptidyl site where the tRNA dissociates leaving the amino acid at
the peptidyl site.
 Again, the ribosome now moves along the mRNA to expose the next codon and this process continues until the mRNA shows one
of the terminatory codons UAA or UAG or UGA. These terminatory codons are called non-sense codons, as they do not code for
any particular amino acid.
 The transfer of data contained in the mRNA to form proteins is called translation.
 When only one ribosome is attached to the mRNA it is called monosome when there are more than one ribosome attached to the
mRNA it is called polysome.

Antibiotic Tetracycline Chloramphenicol Aminoglycoside Macrolide
Soil actinomycetes
Source Streptomyces Venezuelae Streptomycin- S.griseus Erythromycin- S.erythreus
S.aureofaciens
Spectrum of Active only against aerobes. Active against mainly gram +
Broad spectrum Broad Spectrum
activity Bactericidal organisms.
It binds to the 30’s subunit,
the 50’s subunit as well to the
30s-50s interface. They
freeze initiation of protein It combines with 50s ribosomal
It acts by interfering with the
synthesis, prevent polysome subunit and interferes with
Binds to the 30’s transfer of the elongating peptide
formation. Binding to the translocation of the elongated
ribosomal subunit and chain to the newly attached
30s-50s interface causes peptide chain back to the
Mechanism inhibits the attachment amino acid at the ribosome
distortion of the mRNA peptidyl site. The ribosome fails
of action of aminoacid-tRNA mRNA complex. Therefore, it
codon resulting in wrong to move along the mRNA to
complex to the mRNA- inhibits peptide bond formation.
amino acids entering the expose the next codon and thus
ribosomal complex. It specifically attaches to 50’s
peptide chain and these protein synthesis is terminated
ribosome.
defective proteins affect the prematurely.
integrity of the cell
membrane resulting in cell
death.

A. Inactivating enzymes
Due to plasma mediated that adenylate/acetylate or
synthesis of a phosphorylate the Resistant organisms produce
Resistant organisms produce
protection protein that antibiotic. erythromycin esterase that
Mechanism Chloramphenicol acetyl
protects the ribosomal B. Decrease in the affinity inactivates the drug or the
of Resistance transferase, which inactivates the
binding site from TC’s. of the ribosomal protein organisms become less
drug.
Posess cross resistance that binds the antibiotic. permeable to the drug.
with chloramphenicol. C. Porins become less
permeable to the drug.
TC’s have chelating

property- form
Oral form is Chloramphenicol All ionize in solution and are Erythromycin is acid labile. To
Pharmacokin insoluble and
palmitate. Parenteral form is not absorbed orally. Excreted protect it from the gastric acid it
etics unabsorbable
Chloramphenicol Succinate. unchanged in urine. is given an enteric coat.
complexes with calcium
and other metals.
Adverse a. Liver damage a. Gray baby syndrome: seen in a. Ototoxicity a.Gastrointestinal distress
Effects b. Kidney damage infants because they lack the  Cochlear damage
Fanchony c. Photo toxicity glucoronic acid required for  Vestibular damage a. Hepatitis.
syndrome. d. Deposition of conjugation with b. Nephrotoxicity

Shown by calcium tetracycline Chloramphenicol. c. Neuromuscular

only chelate in bones and b. Super infections blockade
doxycycline teeth. c. Bonemarrow depression-
e. Vestibular toxicity- aplasticanemia,
Ataxia, vertigo and agranulocytosis,
nystagmus thrombocytopenia.
(involuntary eye
ball moment).
f. Diabetes insipidus-
Demeclocyclin
a. Used to treat
infections, when the a. Tuberculosis
a. Typhoid (enteric fever) a. Atypical pneumonia caused by
causative organism is b. SABE
b. H.influenzae meningitis mycoplasma pneumoniae
Uses unknown. c. Plague
c. Anaerobic infections b. Diphtheria, tetanus, Syphilis,
b. venereal diseases d. Tularemia sub acute
D.Intraocular infections. etc...
c. Cholera, plague, Bacterial endocarditis (sabe)
Brucellosis, etc.

Tetracyclines:-
More stable & long acting ------ 6-deoxy tetracycline, methacycline, doxycline minocycline.
Miscellaneous Antibiotics:-
1) Lincosamide antibiotics: - clindamycin M.O.A & spectrum of activity is similar to erythromycin & also exhibits partial cross resistance.
2) Glycopeptide Antibiotics: - E.g.:- Vancomycin acts by inhibiting cell wall synthesis. It binds to the terminal dipeptide sequence of
peptidoglycon units at the cell membrane & their cross linking to form the cell wall does not take place.
Uses: - In MRSA infections.
3. Polypeptide Antibiotics: - Bactericidal agents have detergent like action on cell membrane. They have high affinity for phospholipids &
thus they orient between phospholipid & the protein layers in gram negative organisms, resulting in formation of pseudopore. As a result
aminoacids leak out leading to cell death. E.g.:- Polymyxin B, Bacitracin, Colistin, Thyrotricin, Capreomycin, Nespirocin.
Urinary Antiseptics: - Nitrofurantoin, Hexamine

Urinary Analgesic: - Phenazopyridine HCL.
ANTITUBERCULAR AGENTS
Tuberculosis is caused by mycobacterium tuberculosis.

First line drugs: - INH, Rifampicin, Pyrazinamide, Ethambutol.
Second line drugs: - Ciprofloxacin, Azithromycin.

DRUG M.O.A PHARMACOKINETICS A.R
It undergoes Acetylation At lowPH-

P-amino salicylic
Prevents incorporation of PABA decarboxylation Hypersensitivity reactions
acid
At highPH-oxidation
Inhibits the synthesis of mycolic acid

Peripheral neuritis due to renal excretion of
INH (imp component of mycobacterial cell Acetylated by liver.
vit B6 ,Hepatitis
wall)
Hepatitis respiratory syndrome, Cutaneous

Inhibits DNA dependent RNA Metabolized in liver to an active
Rifampicin syndrome, Flu syndrome, Abdominal
polymerase deacteylated metabolite.
syndrome.
Not known penetrates inflamed

Hepatatoxicity, Hyperuricaemia (due to
Pyrazinamide meninges in treatment of tuberculosis Penetrates CSF & metabolised in liver.
inhibition of uric acid tubular secretion)
meningitis.
Ethambutol Interferes with mycolic acid

75% of oral dose is absorbed & Loss of visual acuity, field effects due to
(d isomer is more incorporation in cell wall & inhibits
temporarily stored in R.B.C. optic neuritis.
patent) RNA synthesis.

Antitubercular Antibiotics: - Cycloserine, Capreomycin, Viomycin, Rifampicin.
Effective treatment :- (Sterilization period).

INH 300mg, Rifampicin 600mg, Pyrazinamide 25mg/kg (for 8 weeks)
(Maintainance period) INH & Rifampicin (for 16 weeks)
ANTILEPROTIC AGENTS
Leprosy is called by Mycobacterium leprae.
Drug M.O.A Pharmacokinetics A.R
Completely absorbed orally, gets Mild Hemolytic anemia,

Dapsone Inhibits incorporation of PABA in to folic acid
concentrated in skin, liver & kidney. gastric intolerance.
Inhibits bacterial cell wall synthesis by inhibiting the

Cycloserine enzyme that racemises h-alanine and links two D-
Alanine residues.
Binds with nucleic acids & concentrate in Well tolerated reddish

Clofazimine Gets accumulated in tissues
reticuloendothelial tissue & interfere with template Block discolouration of
(dye) especially in crystalline form.
function of DNA. skin

ANTIFUNGAL AGENTS
Classification:-
1. Azoles: - Clotrimazole, Ketaconazole, Miconazole.
2. Allylamine & related compounds: - Tolnafate, Terbinafine.
3. Fatty acids: - Propionic acid, Triacetin, Salicylic acid.
4. Phenol & their derivatives: - Haloprogin, Cyclopirox.
5. Nucleosides: - Flucytosine.
6. Antibiotics: - Nystatin, Amphotericin, Candidicin.
7. Heterocyclic Benzofuran: - Griseofulvum.
Drug Amphotericin B Griseofulvin Imidazoles & triazoles. Flucytosine Tolnafate

Mechanism Has high affinity for It interferes with They inhibit the fungal It is taken up by fungal Interfere with fungal
of action ergosterol present in mitosis and causes cytochrome P450 enzyme cells and then converted ergosterol Biosynthesis
fungal cell membrane. abnormal metaphase lanosterol 14- into 5-FU and then to 5- by epoxidation of
Binds to it forming a configurations. The demethylase required for fluorodeoxyuridylic acid squalene by the enzyme
micropore, through daughter nuclei fail to conversion of lanosterol which is an inhibitor of squalene epoxidase.
which amino acids move apart and thus to ergosterol. This thymidylate synthetase
leak out leading to cell cell division is arrested results in membrane required for the
death. at metaphase. abnormalities in the synthesis of thymidylic
fungus. acid, which is a
component of DNA.

Spectrum Candida albicans, Dermatophytes such as Dermatophytes, candida Cryptococcus Dermatophytes candida.
of activity Histoplasma Epidermophyton, albicans, nocardia, neoformans, candida,
capsulatum, etc. Trichophyton, leishmania, etc. torula, aspergilllus,
microsporum, etc. chromoblastomyces.
Pharmacoki Administered both Gets deposited in the Administered orally
netics orally and Keratin forming cells of
prarenterally. skin, hair and nails.
Absorption is enhanced
by micronisation.
Adverse Nephrotoxicity- Peripheral neuritis, Inhibits CYP3A4, Leucopenia,
effects azotemia, reduced transient leukopenia, thereby raising the blood thrombocytopenia.
g.f.r acidosis. albuminuria. levels of drugs like
warfarin, terfenadine.
Uses Systemic mycoses and Dermatophytosis. Systematic and topical Chromoblastomycosis. Athlete’s foot
Leishmaniasis. infections. ringworm.
Antiviral agents: Infectious virus particle is called virion. DNA containing virus
Adenovirus Many types Respiratory tract & eye infections
Herpes virus H.simplex I & II vercilla zoster Herpes zoster Encephalitis chicken pox shingles
Papora virus Human wart virus polyoma virus Human wart salivary gland infection
Pox virus Vaccine Small pox, chicken pox, cow pox, eczema.

RNA CONTAINING VIRUS:-
Orthomyxovirus Influenza A,B,D Influenza A,B,D
Picornovirus Rhinovirus Respiratory disease poliomyletis
Retrovirus Type C Leukemia

Type B Mammary tumor
Type D Monkey Aids
HIV AIDS
Rhabdovirus Rabies virus Rabies
Togavirus Rubella virus Rubella
Unclassified virus Hepatitis A,B,&C viruses Hepatitis
CLASSIFICATION:-
A. Anti-herpes virus. Most of the antiviral drugs of this class act by inhibiting DNA polymerase. E.g.:- Idoxuridine, acyclovir,
Ganciclovir, Foscarnet.
B. Anti-retro virus. Non-nucleoside reverse transcriptase inhibitors. E.g.:- Zidovudine (AZT), Didanosine, and Zalcitabine.
Nevirapine, Delaviridine.
Protease inhibitors. E.g.:- Saquinavir, Indinavir.
C. Anti-influenza virus. E.g.:- amantadine.
D. Others. E.g.:- interferons, ribavirin.

Drug Mechanism of action Mechanism of resistance Adverse effects Uses
It is phosphorylated by viral
thymidylate kinase to monophosphate, Resistant viruses decrease
then to triphosphate. The triphosphate the amount of thymidylate
is an inhibitor of viral DNA kinase required for the 1. H.simplex
Idoxuridine polymerase, causing inhibition of viral activation of the drug. keratoconjuctivities.
DNA synthesis and it is also Decrease in the affinity of (Cytomegalblasto virus)
incorporated in the DNA resulting in DNA polymerase for the
faulty DNA, which code for wrong drug.
proteins.
A phosphonoformate derivative binds

to the pyrophosphate binding sites of Hypokalemia,
CMV retinitis, varicella
Foscarnet viral DNA polymerase and reverse hypomagnesia, renal
zoster infections.
transcriptase to prevent the toxicity.
incorporation of nucleotides into DNA.
On phosphorylation in the body into

zidovudine triphosphate, it inhibits the Decrease in the affinity of Anaemia,
Zidovudine,
enzyme viral reverse transcriptase reverse transcriptase for the neutropenia, AIDS
Stavudine
which is required for the synthesis of drug. myopathy.
DNA from viral RNA.

An aspartic enzyme protease encoded

by HIV is involved in the production of G.i.t intolerance,
structural protein and enzymes of the asthenia, paresthesia Used to treat later stages
Saquinavir
virus. Inhibition of the aspartic enzyme and exacerbation of of AIDS infections.
by Saquinavir will deprive the virus of diabetes.
the essential proteins.
It acts on an ion channel M2 and Insomnia, dizziness,
Amantadine influenzaA2, Parkinson’s.
interferes with the step of uncoating. hallucination.
Its mono and triphosphate derivatives
Ribavirn InfluenzaA & B, measles.
inhibit GTP and viral RNA synthesis.
Converted to monophosphate by viral
Acylclovir Herpes infections.
thymidine kinase.
Interferons: - are the cytokines produced by the body in response to viral infections. They bind to cell specific receptors and interfere with
various stages of viral replication such as uncoating, penetration of virus into the host cell, synthesis of viral protein. Interferon’s bind to
receptors and induce production of Interferon induced protein that has antiviral effects. They are active against both DNA & RNA viruses. They
are host specific. They are indicated for:-
 Chronic hepatitis B & C
 AIDS related Kaposi sarcoma (cancer & aids)
 Hairy cell leukemia.
 Rhinoviral cold.
Adverse effects include myelosupression, neurotoxicity, etc.

ANTIMALARIAL AGENTS
Malaria is caused by four species namely

1. plasmodium vivax,
2. P.falciparum,
3. P.malariae and P.ovale.
4. P.falciparum does not have secondary Schizontic stage.
CLASSIFICATION:-
1. Cinchona Alkaloids: - Quinine

2. 4 Amino quinoline: - Chloroquine, Amodiaquine
3. 8 Amino quinoline: - Primaquine, pamaquine
4. 9 Amino Acridines: - Quinacrine
5. Biguanides & dihydrotriazines: - Chlorguanide
6. Pyrimidines: - Pyrimethamine
7. Sulfonamides: - Sulfadoxine, Dapsone, Sulfamethopyrazine
8. Quinoline methanol: - Mefloquine
9. Phenanthrene methanol: - Halofantrine
10. Miscellaneous: - Qinghaosu, tetracycline’s.

DRUG CHLOROQUINE MEFLOQUINE QUININE CHLOROGUANIDE

PROGUANIL
Mechanism It moves into acidic vesicles of Inhibits the enzyme haem Inhibits the enzyme It is cyclised in the body to a
of action the parasite, raises pH and polymerase. haempolymerase. triazine derivative, which inhibits
inhibits the degradation of plasmodial dihydrofolate
Hemoglobin by Iysosomal reductase, which is essential for
products. It inhibits the enzyme the synthesis of folate
haempolymerase that coenzymes.
polymerizes toxic free haem to
nontoxic haemzoin.
Resistance Increased expression of
It occurs due to the increased Increased expression of an It occurs by mutation resulting in
efflux of the drug from the an efflux transporter efflux transporter similar to decrease in the affinity of the
parasitic vesicles. similar to human human transporter, P- DHFRase for drug.
transporter, P- glycoprotein.
glycoprotein.
Spectrum of Erythrocytic stages of all the Blood Schizonticide Blood schizonticide on all the Slow acting Erythrocytic
activity four plasmodial species. Against P.Falciparum & four plasmodial species. Schizonticide.
P.vivax.
Adverse Liver damage. Gastrointestinal Cinchonism-tinnitus, Mild abdominal upset, hematuria.
effects disturbance, giddiness, paraplegia, metallic taste.
insomnia. Prolongation Cardiac arrhytmias, blood
of QT intervals leading to dyscriasis can also occur.(bone
arrhythmias. marrow depression)
Uses Also active Entamoeba Treatment of an acute Resistant falciparum malaria, Prophlaxis of malaria.
histolytica & Giardia lamblia. attack. cerebral malaria.

 Pyrimethamine also acts by inhibiting plasmodial dihydrofolate reductase and it is a more potent than chlorguanide.
 Primaquine acts on the exoerythrocytic stages and is highly active against the gametocytes and hypnozoites.
 It causes hemolytic anemia in patients with G6-PD deficiency.
 Halofantrine, a blood schizonticidal agent is active against multiresistant.
 P.falciparum. Cross-resistance is seen between Halofantrine and mefloquine.
 Artemesinin, a sesquiterpine lactone is active against multiresistant.
 P.falciparum. It acts by interacting with haem and generated free radicals that binds to the membrane proteins and damages the parasite.
ANTIAMOEBIC DRUGS
Ameobiasis is a protozoal disease caused by Entamoeba Histolytica.

Intestinal amoebiasis: - Here E.Histolytica invade the intestinal wall of the colon.
Extra intestinal amoebiasis: - It affects liver, lungs & Brain.
E.Histolytica exists in two forms
1. Cysts: - inactive form
2. Trophozite: - active form
CLASSIFICATION:-
A. Tissue amoebicides
 For both intestinal and extra intestinal amoebiasis. Nitroimidazoles. E.g.: Metronidazole, tinidozole rhimostrozole. Alkaloids. E.g. :
emetine
 For extra intestinal amoebiasis only. E.g. : chloroquine

B. Luminal amoebicides
 Amide. E.g. : Diloxanide furoate
 8-Hydroxyquinolines. E.g.: Quiniodochlor, Diiodohydroxyquin clioquinol.
 Antibiotics. E.g.: Tetracycline’s.
Drug Metronidazole, tinidozole Emetine Diloxanide furoate Quiniodochlor, Diiodohydroxyquin
Mechanism The nitro group of the compound It inhibits protein by It prevents the formation Kill the cyst forming trophozoites in
of action is reduced to intermediate arresting the intraribosomal of cysts. From the intestinal tract by chelating ferrous
compounds that cause cytotoxicity translocation of peptidyl trophozoites. Interferes ions which are essential for protozoal
by damaging DNA. tRNA aminoacid complex. with protein synthesis. metabolism.
Spectrum Anaerobic organisms. Kills trophozoites but has no Kills trophozoites Active against entamoeba, Giardia
of activity action on cysts. responsible for cyst trichomonas and some fungi.
formation.
Adverse G.i.t disturbances, CNS Hypo tension, tachycardia, Flatulence, itching is Iodism. Prolonged use caused ‘sub
effects symptoms. ECG changes and occasional. acute myelopatic neuropathy’
myocarditis. (SMON).
Uses Amoebiasis, Giardiasis, Liver fluke infestation Asymptomatic amoebiasis. Amoebiasis, Giardiasis, monolial
Ulcerative gingivitis, H.Pylori vaginitis, fungal infections.
infections.

Suramin sodium: - anionic in nature & binds with cationic sites in proteins & enzymes in glycolytic pathway.
Sodium stilbogluconate: - These pentavalent antimonials get converted to trivalent antimonials, which inhibit phosphofructokinase, an enzyme
catalyses a limiting step in glycolysis.
Leishmaniasis is caused by Leishmania donovani and the drugs used to treat are Sodium Stilbogluconate, Meglumine, pentamidine,
Amphotericin B, Ketoconazole and allopurinol. Severe form of leishmaniasis is Kala-azar.
ANTHELMINTICS
These agents destroy or eliminate parasitic worms (helmints) from GIT/body tissues.
Anthelmintic may act as:-

1) Vermifuge :- expels worms by paralyzing them
2) Vermicide :- kill worms in the body
3) Some may also impair the egg production process in worms.

Drug Mebendazole/Albendazole Pyrantel pamoate Piperazine Diethyl carbamazine

Inhibit glucose uptake, It causes activation of nicotinic It causes neuromuscular
Alteration of the
thereby depleting glycogen cholinergic receptors in the worm blockade by antagonizing Ach
Microfilariae (MF)
Mechanism stores. Bind with affinity to resulting in persistent action and causes
membrane so that they are
of action micro tubular protein B- depolarization, which leads to hyperpolarisation, which leads
readily phagocytosed by
tubulin and inhibit its paralysis. Worms are then to paralysis. Worms are then
tissue fixed monocytes.
polymerization. expelled. expelled.
Round worm, hook worm,

Spectrum of Hook worm Round worm, thread Mf of Wuchereria bancrofti,
tirichuriasis, pinworm & Round worm,
activity worm. Brugia malayi, o.volvulus.
guinea worm.
Drug Levamisole Niclosamide Praziquantel Ivermectin

Causes leakage of intracellular
It inhibits oxidative
calcium from the membranes Potentiation of GABAergic
Mechanism It is an immunomodulator- phosphorylationin mitochondria
leading to paralysis. The lose transmission in worms
of action restores T-cell function and thereby interferes with
grip of the intestine and are leading to paralysis.
anaerobic generation of ATP.
expelled.
Spectrum of Ascaris & stronglyloides Taenia saginata, T. solium, Onchocerca volvulus, which
Tape worms schistosomiasis.
activity larvae. hymenlepsis nana. causes river blindness.
Thiabendazole acts by inhibiting fumarate reductase. In T.C.A. cycle useful in strongylodias.

ANTICANCER AGENTS
These are cytotoxic drugs either kill cancer cells or modify their growth cell cycle:
G1 (pre-synthetic phase)

S – Synthesis of DNA

G2 – Post synthetic phase

M - Mitosis phase
 
G1 G1 (daughter cells)

G0 – Resting phase
 The cells in resting stage are those that are non-proliferating.

 These remain quiescent, but they can be recruited in the cell cycle when stimulated later.
 Cytotoxic drugs are either cell cycle specific or cell cycle non-specific (they kill both resting as well as dividing cells).
o Cytotoxic drugs that are cell cycle specific include drugs like Methotrexate, Cytarabine, 6-Mercaptopurine, 6-Thioguanine,
Mitomycin, Doxorubicin act on the S phase, drugs like Daunorubicin, Bleomycin, etoposide that act on the G2, drugs like
vincristine, Vinblastine and paclitaxel that act on the M phase.
o Cytotoxic drugs that are cell cycle nonspecific include nitrogen mustards, cyclophosphomide, Chlorambucil, 5-FU, L-asparginine,
Cisplatin, Procarbazine, Dacarbazine, etc.

CLASSIFICATION:
A. Alkylating agents: These can be further classified into:
a. Nitrogen mustards. E.g.: Mustine, Cyclophosphamide, Ifosfamide, chlorambucil
b. Ethyleneimine. E.g.: Thiotepa
c. Alkylsulfonate. E.g.: Busulphan
d. Nitrosourea. E.g.: Carmustine, Lomustine (they cross B.B.B & used in Brain tumors)
e. Triazine. E.g.: Dacarbazine.
f. Hydrazine. E.g.: Procarbazine
B. Antimetabolites
a. Folate antagonist. E.g.: Methotrexate (amethopterin)
b. Purine antagonist. E.g.: 6-Mercaptopurine, Azathiopurine, 6-Thioguanine
c. Pyrimidine antagonist. E.g.: 5-Fluorouracil, Cytarabine.
C. Vinca alkaloids. E.g.: Vincristine (oncovin), Vinblastine.
D. Taxanes. E.g.: paclitaxel, Taxotere.
E. Epipodophyllotoxin. E.g.: etoposide, Teniposide Daunorubicin.
F. Antibiotics. E.g.: Actinomycin D (Dactinomycin), Doxorubicin Bleomycins, Mitomycin.
G.Miscellaneous. E.g.: cisplatin, L-asparaginase.

TOXICITY OF ANTICANCER DRUGS:-

They have a profound effect on rapidly proliferating cells, the most important target of action are the nucleic acids and their precursors; rapid
nucleic acid synthesis occurs during cell division. The different Toxicities that arise from Anticancer agents are:-
1. Bone marrow depression (Myelo suppression / Blood dyscriasis) resulting in granulocytopenia, agranulocytosis, thrombocytopenia,
Aplastic anemia
2. Lymphocytopenia and the suppression of Humoral & Cell mediated immunity.
3. Stomatitis, diaarohea, shedding of mucosa, hemmorages
4. Skin: Alopecia
5. Inhibition of gonadal cells causes oligozoospermia& impotence in males.
6. Teratogenic in nature.
7. Hyperuricaemia
Virus: - Epstein barr virus is responsible for production of cancer

Genes: - Oncogene is responsible for production of cancer
ALKYLATING AGENTS: -
 These compounds produce highly reactive carbonium intermediates, which transfer alkyl groups to cellular macromolecules by forming
covalent bonds. The position 7 of guanine residues in DNA is highly susceptible because it is highly nucleophilic.
 This results in cross linking / abnormal base pairing / scission of DNA strand.
 Crosslinking of nucleic acids can also take place.
 In case of Meclorethamine (mustine), Aziridinium is the intermediate formed.
 In case of Cyclophosphamide, Phosphoramide & Acrolein are the intermediates formed.

 Phosphoramide is the active metabolite; While Acrolein is toxic to the Urinary bladder.
 (Mercapto sulphonic acid is given to avoid damage of urinary bladder due to Acrolein)
 Ifosfamide is the congener of Cyclophosphamide.
 Thiotepa produces Aziridinium as an intermediate.
 Alkyl sulfonates undergo a process known as “Sulphur Stripping” to react with cellular macromolecules & is used in Myeloid Leukemia.
 Carmustine & Lomustine crosses B.B.B. and hence used in treatment of Brain Tumors
ANTIMETABOLITES: - These compounds prevent biosynthesis or utilization of normal cellular macromolecules.
FOLATE ANTAGONISTS: -
 Methotrexate (Amethopterine) / Aminopterine act by inhibiting dihydrofolate reductase (DHFR), which is essential for the conversion of
Dihydrofolic acid to Tetrahydrofolic acid, & step which has to occur if synthesis of folate co-enzymes has to proceed.
 Thus, they inhibit the synthesis of thymidilic acid, which is a component of the DNA.
 Administration of Folinic acid counteracts toxicity of Methotrexate.
 Methotrexate acts on S phase of the cell division.
PURINE ANTAGONISTS: -
 6-mercaptopurine, 6-thioguanine are converted to monoribonucleotide by Hypoxanthine guanine phosphoribosyl transferase (HGPRT).
 Tumor cells lack the enzyme HGPRT develop resistance to the above drugs.Monoribonucleotides inhibit the conversion of 5-
Phosphoribosylpyrophosphate to 5-phosphoribosylamine, which is required for the synthesis of purines.

PYRIMIDINE ANTAGONISTS: -
 5-fluorouracil is converted in the body to the corresponding nucleotide.
 5-fluro-2-deoxyuridine monophosphate, which inhibits thymidilate synthetase & blocks the conversion of deoxyuridilic acid to deoxy
thymidilic acid. Thus, it inhibits the synthesis of DNA.
 Fluorouracil itself gets incorporated in to nucleic acids and this may contribute to its toxicity.
Cytarabine: -
 It is phosphorylated in the body to the corresponding nucleotide, which inhibits DNA synthesis.
 The triphosphate of cytarabine is an inhibitor of DNA polymerase & blocks the generation of cytidilic acid.
Vinca alkaloids: -
 These are mitotic inhibitors that bind to the micro tubular protein “tubulin”, prevent its polymerization & assembly of microtubules &
thus cause disruption of mitotic spindle &interfere with cytoskeletal function.
 Therefore the chromosomes fail to move apart during mitosis.
 They are cell cycle specific and they act in metaphase phase. E.g.: vincristine & vinblastine
Taxanes: -
 Paclitaxel enhances polymerization of tubulin. As a result, the microtubules are stabilized & their depolymerisation is prevented.
 This stability results IU inhibition of normal dynamic reorganization of the microtubule network that is essential for vital interphase &
mitotic functions. Abnormal arrays or bundles of microtubules are produced throughout the cell cycle.
 The major adverse effects seen are “stocking & glove” neuropathy.
 Epipodophyllotoxins such as etoposide arrest cells in the G2 Phase & causes DNA breaks by stimulating DNA topoisomerase-2

DRUG MECHANISM OF ACTION
Actinomycin D ( Dactinomycin ) It inhibits DNA topoisomerase-2 & also interrelates in DNA, causing DNA breaks
Daunorubicin(Rubidomycin),Doxorubicin It inhibits DNA topoisomerase-2& generates quinone type free radicals.
Mitomycin It is converted in the body to act as an alkylating agent.
It blocks the conversion of ribonucleotides to deoxy ribonucleotides by inhibiting the

Hydroxyurea
enzyme ribonucleoside diphosphate reductase & thus interferes with DNA synthesis.
After metabolic activation, it depolymerises DNA & causes chromosomal damage.

Procarbazine
Inhibition of DNA synthesis occurs.
The enzyme L-Asparginase degrades l-asparginase to L- aspartic acid, depriving leukemic

L-asparginase
cells of an essential metabolite & this may cause cell death.
A platinum co-ordination complex is hydrolysed intracellularly to produce a highly reactive

Cisplatin
moiety that causes cross-linking of DNA.

DIAGNOSTIC TESTS OF DISEASES:-
Diseases Test Deficiency disorder Drug given

1.Diptheria Shick test 1.Hypocalcaemia Calcium gluconate i.v.
2.Haemophilus Ducrey test 2.Addisons disease Corticosteroid
3.Leprosy Lepromin test 3.Anaemia Ferrous sulphate
4.Scarlet fever Dick test
5.Syphilus VDRL & Widal test
6.Tuberculosis Tuberculin test
7.Typhoid Widal test
Toxicity Drugs
1.Paracetamol, Chloroform Acetyl cysteine
2.Copper,Gold Penicillamine
3.Arsenic Dimercaprol
4.Lead Calcium EDTA
5.Iron Desferroxamine
6.Benzodiazepines Flumenazil
7.CO,CO2 Oxygen
8.Caffeine, Theophylline Esmolol

PHARMAROCKS
GPAT STUDY MATERIAL
ANTIBIOTICS & CHEMOTHERAPY

PHARMACOLOGY
PHARMAROCKS GPAT SUCCESS TEST SERIES

ORGANISE BY MR. AMAR RAVAL
PHARMAROCKS GPAT SUCCESS TEST SERIES-2016: THE WAY OF SUCCESS IMP STUDY MATERIAL
ANTIBIOTICS BY CLASS
GENERIC NAME BRAND NAMES COMMON USE POSSIBLE SIDE EFFECT MECHANISM OF ACTION
AMINOGLYCOSIDES
Amikacin Amikin Infections caused by Hearing loss Binding to the
Gentamicin Garamycin Gram-negative bacteria, such as Vertigo bacterial 30S ribosomal subuni
Kanamycin Kantrex Escherichia coli and Klebsiella Kidney damage t (some work by binding to
Neomycin Neo-Fradin particularly Pseudomonas the 50S subunit), inhibiting the
Netilmicin Netromycin aeruginosa. translocation of the peptidyl-
Tobramycin Nebcin Effective against Aerobic bacteria tRNA from the A-site to the P-
Paromomycin Humatin (not obligate/ facultative anaerobes) site and also causing
andtularemia. misreading of mRNA, leaving
the bacterium unable to
synthesize proteins vital to its
growth.
ANSAMYCINS
Geldanamycin Experimental,
Herbimycin As antitumor antibiotics
CARBACEPHEM
Loracarbef Lorabid Discontinued Prevents bacterial cell division by
inhibiting cell wall synthesis.

CARBAPENEMS
Ertapenem Invanz Bactericidal for both Gastrointestinal upset and Inhibition of cell wall
Doripenem Doribax Gram-positive and Gram-negative diarrhea synthesis
Imipenem Cilastatin Primaxin organisms and therefore useful for Nausea
Meropenem Merrem empiric broad-spectrum antibacterial Seizures
coverage. (Note MRSA resistance to Headache
this class.) Rash and allergic reactions
CEPHALOSPORINS (FIRST GENERATION)
Cefadroxil Duricef Good coverage against Gastrointestinal upset Same mode of action as
Cefazolin Ancef Gram positive infections. and diarrhea other beta-lactam antibiotics:
(discontinued) Nausea disrupt the synthesis of
Cefalotin or Cefal Keflin (if alcohol taken thepeptidoglycan layer of
othin (discontinued) concurrently) bacterial cell walls.
Cefalexin Keflex Allergic reactions
CEPHALOSPORINS (SECOND GENERATION)
Cefaclor Distaclor Less gram positive cover, improved Gastrointestinal upset and Same mode of action as
Cefamandole Mandol gram negative cover. diarrhea, Nausea other beta-lactam antibiotics:
(discontinued) (if alcohol taken disrupt the synthesis of
Cefoxitin Mefoxin concurrently) thepeptidoglycan layer of
(discontinued) Allergic reactions bacterial cell walls.

Cefprozil Cefzil
Cefuroxime Ceftin, Zinnat
(UK)
CEPHALOSPORINS (THIRD GENERATION)
Cefixime Suprax Improved coverage of Gastrointestinal upset and Same mode of action as
Cefdinir Omnicef, Gram negative organisms, except diarrhea Nausea other beta-lactam antibiotics:
Cefdiel Pseudomonas. Reduced Gram (if alcohol taken Disrupt the synthesis of
Cefditoren Spectracef positive cover. concurrently) thepeptidoglycan layer of
Cefoperazone Cefobid Allergic reactions bacterial cell walls.
(discontinued)
Cefotaxime Claforan
Cefpodoxime Vantin
Ceftazidime Fortaz
Ceftibuten Cedax
Ceftizoxime Cefizox
(discontinued)
Ceftriaxone Rocephin

CEPHALOSPORINS (FOURTH GENERATION)
Cefepime Maxipime Covers pseudomonal infections. Gastrointestinal upset Same mode of action as
and diarrhea other beta-lactam antibiotics:
Nausea (if alcohol taken disrupt the synthesis of
concurrently) thepeptidoglycan layer of
Allergic reactions bacterial cell walls.
CEPHALOSPORINS (FIFTH GENERATION)
Ceftaroline Teflaro Used to treat MRSA Gastrointestinal upset Same mode of action as
fosamil and diarrhea other beta-lactam antibiotics:
Allergic reaction Disrupt the synthesis of
thepeptidoglycan layer of
bacterial cell walls.
Ceftobiprole Zeftera Used to treat MRSA Gastrointestinal upset Same mode of action as
and diarrhea other beta-lactam antibiotics:
Nausea (if alcohol taken Disrupt the synthesis of
concurrently) thepeptidoglycan layer of
Allergic reactions bacterial cell walls.

GLYCOPEPTIDES
Teicoplanin Targocid (UK) Active agaist aerobic and anaerobic Inhibiting peptidoglycan
Vancomycin Vancocin Gram positive bacteria including synthesis
Telavancin Vibativ MRSA;
Vancomycin is used orally for the
treatment of C. difficile
LINCOSAMIDES
Clindamycin Cleocin Serious staph-, pneumo-, and Possible C. difficile- Bind to 50S subunit of
Lincomycin Lincocin streptococcal infections in penicillin- related pseudomembranous bacterial
allergic patients, also anaerobic enterocolitis ribosomal RNAthereby
infections; clindamycin topically inhibiting protein synthesis
for acne
LIPOPEPTIDE
Daptomycin Cubicin Gram-positive organisms Bind to the membrane and
cause rapid depolarization,
resulting in a loss of
membrane potential leading to
inhibition of protein, DNA and
RNA synthesis

MACROLIDES
Azithromycin Zithromax, Streptococcal infections, Nausea, Inhibition of bacterial protein
Sumamed, syphilis, vomiting biosynthesis by binding
Xithrone upper respiratory tract infections, diarrhea reversibly to the
Clarithromycin Biaxin lower respiratory tract infections, (especially at high doses) subunit 50S of the
Dirithromycin Dynabac mycoplasmal infections, bacterial ribosome,
(discontinued) Lyme disease Prolonged QT interval There by inhibiting
Erythromycin Erythocin,Erythr (especially erythromycin) translocation of
oped Jaundice peptidyl tRNA.
Roxithromycin
Troleandomycin Tao
(discontinued)
Telithromycin Ketek Pneumonia Visual Disturbance,
Liver Toxicity.[4]
Spectinomycin Trobicin Gonorrhea
Spiramycin Rovamycine Mouth infections
MONOBACTAMS
Aztreonam Azactam Same mode of action as other beta-

lactam antibiotics:
Disrupt the synthesis of

thepeptidoglycan layer of
bacterial cell walls.
Nitrofurans
Furazolidone Furoxone Bacterial
or protozoal diarrhea orenteritis
Nitrofurantoin Macrodantin, Urinary tract infections
Macrobid
PENICILLINS
Amoxicillin Novamox, Wide range of infections; penicillin Gastrointestinal upset Same mode of action as
Amoxil used for streptococcal infections, and diarrhea other beta-lactam antibiotics:
Ampicillin Principen syphilis, Allergy with Disrupt the synthesis of
(discontinued) Lyme disease seriousanaphylactic thepeptidoglycan layer of
Azlocillin reactions bacterial cell walls.
Carbenicillin Geocillin Brain and kidney damage
(discontinued) (rare)
Cloxacillin Tegopen
(discontinued)
Dicloxacillin Dynapen
(discontinued)
Flucloxacillin Floxapen(Sold to
European

generics Actavis
Group)
Mezlocillin Mezlin
(discontinued)
Methicillin Staphcillin
(discontinued)
Nafcillin Unipen
(discontinued)
Oxacillin Prostaphlin
(discontinued)
Penicillin G Pentids
(discontinued)
Penicillin V Veetids
(Pen-Vee-K)
(discontinued)
Piperacillin Pipracil
(discontinued)
Penicillin G Pfizerpen
Temocillin Negaban (UK)
(discontinued)

Ticarcillin Ticar
(discontinued)
PENICILLIN COMBINATIONS
Amoxicillin Augmentin The second component
clavulanate prevents bacterialresistance to
Ampicillin Unasyn the first component
sulbactam
Piperacillin Zosyn
tazobactam
Ticarcillin Timentin
clavulanate
POLYPEPTIDES
Bacitracin Eye, ear or bladder infections; Kidney and nerve Inhibits isoprenyl
usually applied directly to the eye or damage (when given by pyrophosphate,
inhaled into the lungs; rarely given injection) a molecule that carries the
by injection, although the use of building blocks of
intravenous colistin is experiencing a the peptidoglycanbacterial
resurgence due to the emergence cell wall outside of the inner
of multi drug resistant organisms. membrane
Colistin Coly-Mycin-S Interact with the gram

Polymyxin B negative bacterial outer

membrane and cytoplasmic
membrane.
It displaces bacterial counter
ions, which destabilizes the
outer membrane.
They act like a detergent
against the cytoplasmic
membrane, which alters its
permeability.
Polymyxin B and E are
bactericidal even in an
isosmotic solution.
QUINOLONES
Ciprofloxacin Cipro,Ciproxin, Urinary tract infections, Nausea (rare), Inhibit the bacterial DNA
Ciprobay bacterial prostatitis, irreversible damage gyrase or thetopoisomerase IV
Enoxacin Penetrex community-acquiredpneumonia, to central nervous enzyme,
Gatifloxacin Tequin bacterial diarrhea, system(uncommon), There by inhibiting DNA
Levofloxacin Levaquin mycoplasmal infections, tendinosis (rare) replication and transcription.
Lomefloxacin Maxaquin gonorrhea

Moxifloxacin Avelox
Nalidixic acid NegGram
Norfloxacin Noroxin
Ofloxacin Floxin, Ocuflox
Trovafloxacin Trovan Withdrawn
Grepafloxacin Raxar Withdrawn
Sparfloxacin Zagam Withdrawn
Temafloxacin Omniflox Withdrawn
SULFONAMIDES
Mafenide Sulfamylon Urinary tract infections Nausea, vomiting, and Folate synthesis inhibition.
Sulfonamidochrys Prontosil (except sulfacetamide, used for eye diarrhea They are competitive
oidine(archaic) infections, and mafenide and silver Allergy(including skin inhibitors of the
Sulfacetamide Sulamyd, Bleph- sulfadiazine, used topically forburns) rashes) enzyme dihydropteroate
10 Crystals in urine synthetase,
Sulfadiazine Micro-Sulfon Kidney failure DHPS. DHPS catalyses the
Silver sulfadiazine Silvadene Decrease inwhite blood conversion of PABA
Sulfamethizole Thiosulfil Forte cellcount (para-aminobenzoate)
Sulfamethoxazole Gantanol Sensitivity to sunlight to dihydropteroate, a key step
Sulfanilimide (arc in folate synthesis. Folate is
haic) necessary for the cell to

Sulfasalazine Azulfidine synthesize nucleic

Sulfisoxazole Gantrisin acids (nucleic acids are
Trimethoprim- Bactrim, Septra essential building blocks
Sulfamethoxazole of DNA andRNA), and in its
(Co-trimoxazole) absence cells will be unable to
(TMP-SMX) divide.
TETRACYCLINES
Demeclocycline Declomycin Syphilis, Gastrointestinal upset Inhibiting the binding
Doxycycline Vibramycin chlamydial infections, Sensitivity to sunlight of aminoacyl-tRNA to them
Minocycline Minocin Lyme disease, Potential toxicity to mother RNA-ribosome complex.
Oxytetracycline Terramycin Mycoplasmal infections, and fetus during pregnancy
Tetracycline Sumycin,Achro Acne rickettsialinfections, Enamel hypoplasia They do so mainly by binding
mycin V,Steclin * malaria (staining of teeth; potentially to the 30S ribosomal
* Note: Malaria is caused by permanent) subunit in the mRNA
a protist and not a bacterium. transient depression of bone translation complex.
growth
DRUGS AGAINST MYCOBACTERIA

Clofazimine Lamprene Antileprotic
Dapsone Avlosulfon Antileprotic

Capreomycin Capastat Antituberculosis

Cycloserine Seromycin Antituberculosis, urinary tract
infections
Ethambutol Myambutol Antituberculosis
Ethionamide Trecator Antituberculosis Inhibits peptide synthesis
Isoniazid I.N.H. Antituberculosis

Pyrazinamide Aldinamide Antituberculosis
Rifampicin Rifadin, mostly Gram- Reddish-orange sweat, tears, Binds to the β subunit of RNA
(Rifampin in US) Rimactane positive andmycobacteria and urine polymerase to inhibit
transcription
Rifabutin Mycobutin Mycobacterium avium complex rash, discolored urine,
GI symptoms
Rifapentine Priftin Antituberculosis
Streptomycin Antituberculosis Neurotoxicity,ototoxicity As other aminoglycosides
OTHERS
Arsphenamine Salvarsan Spirochaetal infections (obsolete)
Chloramphenicol Chloromycetin Meningitis, MRSA, topical use, or Rarely: Inhibits bacterial protein
for low cost internal treatment. aplastic anemia. synthesis by binding to the
Historic: typhus, cholera. gram 50S subunit of the ribosome
negative, gram positive, anaerobes

Fosfomycin Monurol Acute cystitis in women Inactivates enolpyruvyl

transferase, thereby
blocking cell wall synthesis
Fusidic acid Fucidin
Linezolid Zyvox VRSA Thrombocytopenia
Metronidazole Flagyl Infections caused by anaerobic Discolored urine,headache, Produces toxic free
bacteria; metallic taste, radicals which disrupt DNA
also amoebiasis, nausea ; and proteins.
trichomoniasis, alcohol is contraindicated This non-specific mechanism
Giardiasis is responsible for its activity
against a variety of bacteria,
Amoebae, and protozoa.
Mupirocin Bactroban Ointment for impetigo, cream for Inhibits isoleucine t-RNA
infected cuts synthetase (IleRS) causing
inhibition of protein synthesis
Platensimycin
Quinupristin/Dalf Synercid
opristin
Rifaximin Xifaxan Traveler's diarrhea caused by
E. coli

Thiamphenicol Gram-negative, Gram-positive, Lacks known anemic side- A chloramphenicol analog.

anaerobes. Widely used in veterinary effects. May inhibit bacterial protein
medicine. synthesis by binding to the
50S subunit of the ribosome
Tigecycline Tigacyl
Tinidazole Tindamax protozoan infections upset stomach, bitter taste,
Fasigyn and itchiness
Trimethoprim Proloprim, Urinary Tract Infections
Trimpex
 HI FRIENDS HERE ALL THE DRUGS ARE COVER FROM ANTIBIOTIC SECTION OF PHARMACOLOGY
 MUST PREPARE THIS ALL TABLES
 THEY HELS DURING YOUR GPAT EXAM AS WELL AS IN THE FINAL YEAR OF B.PHARM
 PREPARE WELL ABOUT DRUG AND THEIR SIDE EFFECTS AND MOA.
 ALL THE BEST
 KEEP ROCKING WITH PHARMAROCKS
AMAR M. RAVAL
OWNER: PHARMAROCKS

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 SOLID DOSAGE FORM TABLETS
SOLID DOSAGE FORMS  TABLETS
Syllabus:
Types of tablets
Tablet ingredients: Diluents, binders, disintegrating agents, lubricants, colorants, flavoring and sweeteners.
Principles, materials and equipment involved in drying and mixing of powders, granulation and compression
of tablets.
Layout of a tableting section. Principles of refrigeration-air conditioning, humidification and dehumidification
and fluidization as applied to the manufacturing of tablets.
Principles, processes, materials and equipment involved in coating of dosage forms with sugar, enteric coating
materials and film-formers.
Quality control and standards of coated dosage forms.
Questions:
1. Short note on tablet coatings.
2. Explain the advantages of tablet dosage forms
3. Describe the different methods of preparation of tablets
4. Write a brief note on tablet additives with examples
5. Discuss the different classes of pharmaceutical excipients that go into tablet formulation giving examples
to each class.
6. Draw a sketch of the layout of a tablet manufacturing unit.
7. Differentiate between capsule unit and this. Short note on proper drying of granules.
8. Write an account on the phenomena, processing and importance of enteric coating.
9. Discuss the details of manufacturing of ascorbic acid tablets, explaining each step in the manufacture.
DEFINITION
Tablets may be defined as solid pharmaceutical dosage forms containing drug substances with or
without suitable diluents and prepared either by compression or moulding methods.
This dosage form is intended to be administered through oral route.
Definition according to Indian Pharmacopoeia
“Pharmaceutical tablets are flat or bi-convex discs prepared by compressing a drug or a mixture of
drugs with or without suitable diluents.”
Advantages of tablet dosage form over other oral drug delivery systems:
From patients stand point?
1. They are easy to carry.
2. They are easy to swallow.
3. They are attractive in appearance.
4. Unpleasant taste can be masked by sugar coating.
5. They do not require any measurement of dose. The strip or blister packing has further facilitated
the process of taking the dose by the patient. Moreover, it provides a sealed covering which
protects the tablets from atmospheric conditions like air, moisture and light etc.
6. Some of the tablets are divided into halves and quarters by drawing lines during manufacturing to
facilitate breakage whenever a fractional dose is required.
From the standpoint of manufacturer:
7. An accurate amount of medicament, even if very small, can be incorporated.
8. Tablets provide prolonged stability to medicament. They have the best combined properties of
chemical, mechanical and microbiological stability of all the oral dosage forms.
9. The incompatibilities of medicaments and their deterioration due to environmental factors are less
in tablet forms.
10. Since they are generally produced on a large scale, therefore, their cost of production is relatively
low, hence economical.
11. They are in general the easiest and cheapest to package and ship among all oral dosage forms.

12. Some specialized tablets like enteric coated tablet, sustained release tablets may be prepared for
modified release profile of the drug.
13. Product identification is potentially the simplest and cheapest requiring no additional processing
steps when employing an embossed or monogrammed punch face.
Disadvantages of tablet dosage forms:
(i) Some drugs resist compression into dense compacts, owing to their amorphous nature or flocculent,
low-density character.
(ii) Drugs with poor wetting, slow dissolution properties, intermediate to large dose, or any
combination of these features may be difficult or impossible to formulate and manufacture as a
tablet that will still provide adequate bioavailability.
(iii) Bitter tasting drugs, drugs with objectionable odour, or drugs sensitive to oxygen or atmospheric
moisture may require encapsulation or entrapment prior to compression (if feasible of practical) or
the tablets may require coating.
TYPES OF TABLETS
Tablets are classified according to their route of administration or function. The following are the four
main classification groups:
(A) Tablets ingested orally: (C) Tablets administered by other routes:

(i) Compressed tablets (i) Implantation tablets
(ii) Multiple compressed tablets (ii) Vaginal tablets
(iii) Enteric coated tablets (D) Tablets used to prepare solutions:
(iv) Sugar coated tablets (i) Effervescent tablets
(v) Film coated tablets (ii) Dispensing tablets
(vi) Chewable tablets (iii) Hypodermic tablets
(B) Tablets used in the oral cavities: (iv) Tablet triturates
(i) Buccal cavities
(ii) Sublingual tablets
(iii) Lozenges
(iv) Dental cone
(A) TABLETS INGESTED ORALLY

These tablets are designed to be swallowed except the chewable tablets. The tablets covered in this
category are:
Compressed tablets (C.T.)
These tablets are formed by compression and contain no special coating. They are made from
powdered, crystalline or granular materials, alone or in combination with diluent, binders, disintegrants,
lubricants, antiadherants and in many cases colorants.
These tablets contain water soluble drugs which after swallowing get disintegrated in the stomach and
its drug contents are absorbed in the gastrointestinal tract and distributed in the whole body. E.g.
Aspirin (, Dispirin) paracetamol tablets (Crocin)
Multiple compressed tablets:
These are compressed tablets made by more than one compression cycle:
Layered tablets
Such tablets are prepared by compressing additional tablet granulation on a previously compressed
granulation. The operation may be repeated to produce multilayered tablets of two or three layers.
Special tablet presses are required to make layered tablets such as Versa press. (Stokes/Pennwalt)
These tablets are prepared to separate physically or chemically incompatible ingredients or to produce
repeat action or prolonged action products.
To avoid incompatibility, the ingredients of the formulation except the incompatible material are
compressed into a tablet and then incompatible substance along with necessary excipients are
compressed over the previously compressed tablet.

Sustained action tablets:

These are the tablets which after oral administration release the drug at a desired time and prolong the
effect of the medicament. These tablets when taken orally release the medicament in a sufficient
quantity as and when required to maintain the maximum effective concentration of the drug in the blood
throughout the period of treatment.
E.g. Diclofenac SR tablets.
Enteric coated tablets:
These are compressed tablet meant for administration by swallowing and are designed to by-pass the
stomach and get disintegrated in the intestine only.
These tablets are coated with materials resistant to acidic pH (like cellulose acetate phthalate, CAP) of
the gastric fluid but get disintegrated in the alkaline pH of the intestine. These tablets are made to
release the drug undiluted and in the highest concentration possible within the intestine, e.g. tablets
containing anthelmintic and amoebicides.
Sugar coated tablets:
These are compressed tablets containing a sugar coating. Such coatings are done to mask the bitter and
unpleasant odour and the taste of the medicament. The sugar coating makes the tablet elegant and it
also safeguard the drug from atmospheric effects.
Film coated tablets:
The compressed tablets having a film coating of some polymer substance, such as hydroxy propyl
cellulose, hydroxy propyl methyl cellulose and ethyl cellulose. The film coating protects the
medicament from atmospheric effects. Film coated tablets are generally tasteless, having little increase
in the tablet weight and have less elegance than that of sugar coated tablets.
Chewable tablets:
These are the tablets which are required to be broken and chewed in between the teeth before ingestion.
These tablets are given to the children who have difficulty in swallowing and to the adults who dislike
swallowing.
A number of antacid tablets and multivitamin tablets are prepared as chewable tablets.
For the preparation of chewable tablets mannitol is used as a sweetening base. Since mannitol is
expensive other substances like sorbitol, lactose, chocolate powder, dextrose and glycerin can be
substituted in place of mannitol. These tablets do not require any disintegrating agents to be present in
the formulation.
These tablets should have very acceptable taste and flavour.
E.g. antacid tablets
Vitamin C chewable tablets e.g. CELIN - (Glaxo)
(B) TABLETS USED IN ORAL CAVITY

Buccal tablets:
These tablets are to be placed in the side of the cheek (buccal pouch) where they dissolve or erode
slowly and are absorbed directly in the buccal cavity without passing into the alimentary canal.
Therefore, they are formulated and compressed with sufficient pressure to give a hard tablet e.g.
Progesterone tablets.
Sublingual tablets:
These tablets are to be placed under the tongue where they dissolve or disintegrate quickly and are
absorbed directly without passing into GIT e.g. tablets of nitroglycerin, isoproterenol hydrochloride or
erythrityl tetranitrate.
Lozenges tablets:
These tablets are designed to exert a local effect in the mouth or throat. These tablets are commonly
used to treat sore throat to control coughing in common cold. They may contain local anaesthetics,
antiseptics, antibacterial agents, astringents and antitussives.
These are prepared by compression at a high pressure by the moulding process and generally contain a
sweetening agent, flavouring agent (e.g. peppermint, clove oil) and a substance which produces a
cooling effect (e.g. mentha). E.g. Vicks lozenges.

Dental cones:
These are compressed tablets meant for placement in the empty sockets after tooth extraction. They
prevent the multiplication of bacteria in the socket following such extraction by using slow-releasing
antibacterial compounds or to reduce bleeding by containing the astringent.
These tablets contain an excipient like lactose, sodium bicarbonate and sodium chloride.
These cones generally get dissolved in 20 to 40 minutes time.
(C) TABLETS ADMINISTERED BY OTHER ROUTES

Implantation tablets:
These tablets are placed under the skin or inserted subcutaneously by means of minor surgical
operation and are slowly absorbed. These may be made by heavy compression but are normally made
by fusion. The implants must be sterile and should be packed individually in sterile condition. Implants
are mainly used for the administration of hormones such as testosterone steroids for contraception.
These tablets are very usefully exploited for birth control purpose in human beings.
The disadvantages of implant tablets are their administration changing rate of release with change of
surface area and possibility of tissue reactions.
Vaginal tablets:
These tablets are meant to dissolve slowly in the vaginal cavity. The tablets are typically ovoid or pear
shaped for the ease of insertion. These tablets are used to release steroids or antimicrobial agents. The
tablets are often buffered to promote a pH favorable to the action of a specified antimicrobial agent.
The contains easily soluble components like lactose or sodium bicarbonate.
(D) TABLETS USED TO PREPARE SOLUTIONS

Effervescent tablets:
These tablets along with the active medicament contain ingredients like sodium bicarbonate, citric acid
and tartaric acid which react in the presence of water liberating carbon dioxide and producing
effervescence leading to disintegration of the tablet, thus hastens solution formation and increase the
palatability.
Dispensing tablets:
These tablets provide a convenient quantity of potent drug that can be incorporated readily into
powders and liquids, thus circumventing the necessity to weigh small quantities. These tablets are
supplied primarily as a convenience for extemporaneous compounding and should never be dispensed
as dosage form.
E.g. the drugs commonly incorporated are mild silver potentiate, bichloride of mercury merbromin a
quarternary ammonium compounds.
Hypodermic tablets:
Hypodermic tablets are soft, readily soluble tablets and originally were used for the preparation of
solutions to be injected. These tablets are dissolved in sterile water or water for injection and
administered by parenteral route. These tablets are not preferred now-a-days because the resulting
solution is not always sterile.
Tablet triturates (Moulded tablets):
These are powders moulded into tablets. They are flat, circular discs, usually containing a potent
substance mixed with lactose, lactose and sucrose, dextrose, or other suitable diluent.
Since they are intended to disintegrate very quickly in contact with moisture, water insoluble adjuncts
are avoided. The name ‘tablet triturate’ is appropriate because they usually contain triturations
(trituration = dilution with an inert substance).

TABLET INGREDIENTS
In addition to the active or therapeutic ingredient(s), tablets contain a number of inert materials. The
latter are known as additives or excipients.
They may be classified according to the part they play in the finished tablet.
Group-I: Contains those which help to impart satisfactory processing and compression
characteristics to the formulation. This includes: diluents, binders, glidants and
lubricants.
Group-II: Helps to give additional desirable physical characteristics to the finished tablet. This
includes: disintegrants, colours, and in the case of chewable tablets, flavors and
sweetening agents.
Group-III: In the case of controlled-release tablets, polymers or waxes or other solubility-
retarding materials.
DILUENTS
Objectives of incorporating diluents:
(i) Frequently, the single dose of the active ingredient is small and an inert substance is added to
increase the bulk in order to make the tablet a practical size for compression.
Compressed tablets of dexamethasone contains 0.75 mg steroid per tablet; hence, it is obvious that
another material must be added to make tableting possible.
The dose of some drugs is sufficiently high that no filler is required (e.g. aspirin and certain
antibiotics).
Diluents used for this purpose include dicalcium phosphate (DCP), calcium sulfate, lactose, cellulose,
kaolin, mannitol, dry starch and powdered sugar.
(ii) Certain diluents, such as mannitol, lactose, sorbitol, sucrose and inositol, when present in
sufficient quantity, can impart properties that will help in disintegration of the tablet in the mouth
by chewing. Such tablets are commonly called chewable tablets.
(iii) Diluents used for direct compression formulas give the powder mixture necessary flowability and
compressibility.
(iv) To delay or control the rate of release of drug from the tablet.
Characteristics of an ideal diluents:

1. They must be nontoxic and acceptable to the regulatory agencies in all countries where the product
is to be marketed.
2. They must be commercially available in an acceptable grade in all countries where the product is to
be manufactured.
3. They must be cheap compared to the active ingredients.
4. They must be physiologically inert.
5. They must be chemically stable alone and/or in combination with the drug(s) and/or other tablet
components.
6. They must be free of any unacceptable “microbiological load”.
7. They must be color-compatible (should not produce any off-color appearance).
8. They must have no negative effects on the bioavailability of the drug(s) in the product.
[N.B. e.g. Calcium phosphate as diluent, reduces the bioavailability of some antibiotics like tetracycline.]
Classification of diluents:
DILUENTS
Sugars Polysaccharides Inorganic compounds Miscellaneous compounds
Dextrose Starches Calcium phosphate dihydrate Bentonite
Lactose Modified starch Calcium sulfate dihydrate Polyvinyl pyrrolidone
Sucrose E.g. Sta-RX 1500, Celutab etc. Calcium lactate trihydrate Kaolin
Amylose Cellulose Calcium carbonate Silicone derivatives
Mannitol Cellulose derivatives Magnesium carbonate
Sorbitol Microcrystalline cellulose Magnesium oxide
Inositol (MCC)

CALCIUM SALTS
Example: Dibasic calcium phosphate dihydrate (or dicalcium orthophosphate) (DCP) [CaHPO4,
2 H2O], Calcium sulfate dihydrate (CaSO4, 2H2O).
Advantages:
 Diluents that exist in their common salt form as hydrates, containing appreciable bound water as
water of crystallization. This bound water of calcium sulfate is not released below 800C. They
possess very low concentration of unbound moisture. Hence, these salts are excellent diluents for
water-sensitive drugs. It is superior to anhydrous diluent, which has a moderate to high moisture
demand.
Disadvantages:
 Tetracycline products made with calcium phosphate diluent had less than half the bioavailability of
the standard product. Divalent cation (Ca++) form insoluble complexes and salts with number of
amphoteric or acidic functionality antibiotics, which generally reduces their absorption (which is
also why milk should not be co-administered with these drug).
LACTOSE
Lactose is the most widely used diluent for tablet formulation.
 It is obtained in hydrous and anhydrous form. The anhydrous form, picks up moisture when
exposed to elevated humidity. Such tablets should be packed in moisture proof packets or
containers. When a wet granulation method is employed, the hydrous form of lactose should
generally be used.
 Two grades of lactoses are commercially available:
(i) A 60 to 80 mesh – coarse
(ii) A 80 to 100 mesh – regular grade
Advantages:
1. Lactose has no reaction with most of the drugs, whether in hydrous or anhydrous form.
2. Lactose formulations show good release rates
3. Their granulations are readily dried, and the tablet disintegration times of lactose tablets are not
strongly sensitive to variations in tablet hardness.
4. It is a low cost diluent.
Disadvantages:
1. Lactose reacts with amine drug bases in presence of alkaline lubricants e.g. metal stearates (e.g.
magnesium stearate) and gradually discolours (dark brown) with time due to the formation of
furaldehyde. This reaction is called Maillard reaction.
SPRAY DRIED LACTOSE

Advantages:
1. It is used for direct compression (containing drug + diluent + disintegrant + lubricant)
2. In addition to the direct compression properties, spray dried lactose also has good flow
characteristics. It can usually be combined with as much as 20 to 25% of active ingredients without
losing these advantageous features.
Disadvantages:
1. If spray dried lactose is allowed to dry out and the moisture content falls below the usual 3% level,
the material loses some of its direct compressional characteristics.
2. Spray-dried lactose is especially prone to darkening in the presence of excess moisture, amines, and
other compounds owing to Maillard reactions. Hence, a neutral or acid lubricant should be used.

STARCH
Starch may be obtained from corn, wheat or potatoes. It is occasionally used as a tablet diluent
 USP grade of starch is usually possesses moisture content between 11 to 14%.
 Specially dried types of starch that have a standard moisture level of 2-4% are available, but are
costly. Use of such starches in wet granulation is wasteful since their moisture level increase to 6-
8% following moisture exposure.
DIRECTLY COMPRESSIBLE STARCHES
Sta–Rx 1500 – free flowing, directly compressible starch
– used as diluent, binder, disintegrant
Emdex and Celutab – are two hydrolyzed starches
– contains dextrose 90–92%
Maltose 3–5%
– free flowing and directly compressible
– may be used in place or mannitol in chewable tablets because of their
sweetness and smooth feeling in the mouth.
DEXTROSE (D–Glucose)
Available in two forms: as hydrates and anhydrous forms.
Dextrose may sometimes be combined in formulation to replace some of the spray-dried lactose, which
may reduce the tendency of the resulting tablets to darken.
MANNITOL
Advantages
 Because of the negative heat of solution (cooling sensation in the mouth) its slow solubility, and its
pleasant feeling in the mouth, it is widely used in chewable tablets.
 It is relatively non-hygroscopic and can be used in vitamin formulations.
 Low calorie content and non-carcinogenic.
Disadvantages
 Costly
 Mannitol has poor flow characteristics and usually require fairly high lubricant level.
SORBITOL
It is an optical isomer of mannitol and is sometimes combined with mannitol formulations to
reduce the diluent cost.
Disadvantages: It is hygroscopic at humidities above 65%.
SUCROSE
Some sucrose based diluents are:
Sugar tab – 90 to 93% sucrose + 7 to 10% invert sugar
Di Pac – 97% sucrose + 3% modified dextrins
Nu Tab – 95% sucrose + 4% invert sugar + small amount of corn starch + Mg-stearate
Advantages: They are all used for direct compression.
Disadvantages: All are hygroscopic when exposed to elevated humidity.
MICROCRYSTALLINE CELLULOSE (MCC)

Trade Name: Avicel – is a directly compression material
Two grades are available PH 101  powder
PH 102  granules
Advantages: It acts as diluent and disintegrating agents.

BINDERS
Agents used to impart cohesive qualities to the powdered material are referred to as binders or
granulators.
Objective of incorporating binders
1. They impart a cohesiveness to the tablet formulation (both direct compression and wet–granulation
method) which insures the tablet remaining intact after compression.
2. They improves the free-flowing qualities by the formation of granules of desired size and hardness.
Characteristics of binder
Method-I
Binders are used in dry form in the powder and then moistened with a solvent (of the binder) to form
wet lumps.
Method-II
Binders are often added in solution form. It requires lower concentration of binder.
By Method-I the binder is not as effective in reaching and wetting each of the particles within
the mass of the powder. Each of the particle in a powder blend has a coating of adsorbed air on its
surface, and it is this film of air which must be penetrated before the powder can be wetted by the
binder solution.
Method-III
In direct compression method MCC, microcrystalline dextrose, amylose and PVP are used – those have
good flow property and cohesiveness as well.
It has been postulated that MCC is a special form of cellulose fibril in which individual
crystallites are held together largely by hydrogen bonding. The disintegration of tablets containing the
cellulose occurs by breaking intercrystallite bonds by the disintegrating medium.
STARCH PASTE
Corn starch is often used in the concentration of 10–20%.
Method of preparation
Corn starch is dispersed in cold purified water to make a 5 to 10% w/w suspension and then warming
in water both with continuous stirring until a translucent paste is formed... (Actually hydrolysis of
starch takes place.)
LIQUID GLUCOSE
50% solution in water is fairly common binding agent.
SUCROSE SOLUTION
50% to 74% sugar solution is used as binder. They produce hard but brittle granules. Their
cost is low.
GELATIN SOLUTION
Concentration 10–20% aqueous solution
Should be prepared freshly and added in warm condition other wise it will become solid.
The gelatin is dispersed in cold water and allowed to stand until hydrated. The hydrated mass is
warmed in water bath to dissolve.
CELLULOSIC SOLUTIONS
HPMC (Hydroxy propyl methyl cellulose) Soluble in cold water.
Method of preparation: HPMC is dispersed in hot water, under agitation. The mixture is cooled
as quickly as possible and as low as possible
HEC (Hydroxy ethyl cellulose), HPC (Hydroxy propyl cellulose) are other successful binders.
PVP (Polyvinylpyrollidone) Used as an aqueous or alcoholic solution. Concentration 2% and may vary.

LUBRICANTS
Objectives:
1. Prevents adhesion of the tablet material to the surface of dies and punches.
2. Reduce inter-particular friction, improve the rate of flow of tablet granulation.
3. Facilitate ejection of the tablets from the die cavity.
Examples:
Talc, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oils and polyethylene
glycols (PEG).
Method of addition of lubricants:

1. The lubricant is divided finely by passing it through a 60 to 100 mesh nylon cloth on to the
granulation. In production this is called ‘bolting the lubricant’.
2. After addition the granulation is tumbled or mixed gently to distribute the lubricant without coating
all the particles too well.
* Complete coating will produce dissolution problem.
* Prolonged mixing will produce excessive fines by breaking the granules.
Soluble lubricants
Examples: Sodium benzoate – includes a mixture of sodium benzoate and sodium acetate
Sodium chloride, leucine and carbowax 4000.
Magnesium stearate
Though it is a widely used lubricant it retards disintegration and dissolution. To overcome this
some time surfactants like sodium lauryl sulfate are included.
Lubricants are included to reduce the friction during tablet ejection between the walls of the tablet and
the wall of the die in which the tablet was formed.
Antiadherents are used for the purpose of reducing the sticking or adhesion of any of the tablet
ingredients or powder to the faces of the punches or to the die wall.
Glidants are intended to promote flow of the tablet granulation or powder materials by reducing the
friction between the particles.
An ingredient used for lubrication purpose may possess other two properties as well.
Relative properties of some tablet lubricants:
Material Usual Glidant Antiadherent Lubricant
percent properties properties properties
1. Calcium or Magnesium stearate 1 or less Poor Good Excellent
2. Talc 1–5 Good Excellent Poor
3. Stearic acid 1–5 None Poor Good
4. High melting waxes 3–5 None Poor Excellent
5. Corn starch 5 – 10 Excellent Excellent Poor
Water soluble tablet lubricants

Lubricant Percentage
Boric acid 1
Sodium chloride 5
Sodium benzoate 5
Sodium acetate 5
Sodium oleate 5
PEG 4000, 600 1–4
dl-leucine 1–5

DISINTEGRANTS
Definition
A disintegrant is a substance to a mixture of substances, added to tablet to facilitate its breakup
or disintegration after administration in the GIT.
The active ingredients must be released from the tablet matrix as efficiently as possible to allow
for its rapid dissolution.
Disintegrants can be classified chemically as:
Starches, clays, celluloses, alginates, gums and cross-linked polymers.
Starch
Corn starch, potato starch
For their disintegrating effect starches are added to the powder blends in dry state.
Mode of action:
Starch has a great affinity for water and swells when moistened, thus facilitating the rupture of
the tablet matrix.
Others have suggested that the spherical shape of the starch grains increases the porosity of the
tablet, thus promoting capillary action.
Normally 5% w/w is suggested.
For rapid disintegration 10 – 15% w/w may be taken.
Super disintegrants
Croscarmelose - cross linked cellulose
Crospovidone - cross linked polyvinyl pyrrolidone
Sodium starch glycolate - cross linked starch
Mode of action
Croscarmelose swells 4 to 8 fold in less than 10 seconds
Crospovidone acts by wicking or capillary action.
Sodium starch glycolate swells 7 to 12 folds in less than 30 seconds.
Other materials
Veegum HV, Methyl cellulose, Agar, Bentonite, Cellulose, Alginic acid,
Guargum, and Carboxymethyl cellulose.
 Sodium lauryl sulfate is a surfactant. It increases the rate of wetting of the tablet, thus decreases
the disintegrating time.
Method of blending with powder

The disintegrants are usually mixed with active ingredients and diluents prior to granulation.
Starch may be divided into two portions:
One part – added prior to granulation
Remainder – added prior to compression.
While disintegration the portion of the starch added prior to compression rapidly breaks down the tablet
to granules, and the starch mixed prior to granulation disintegrates the granules into smaller particles.
COLOURING AGENT
Objectives of using colors
(i) It makes the tablet more esthetic in appearance.
(ii) Colour helps the manufacturer to identify the product during its preparation.
All colorants used in pharmaceuticals must be approved and certified by the FDA (food & Drug
Administration). Dyes are generally listed as FD&C (food, Drug & Cosmetic Dyes) dyes and D&C
(Drug & Cosmetic Dyes).

Colour Other Names Color Index (CI, 1971)

D&C Red 22 Eosin Y 45380
FD&C Yellow 5 Tartrazine 15985
FD&C Yellow 6 Sunset Yellow FCF 19140
Yellow Orange 5
FD&C Blue 1 Brilliant Blue FCF 42090
FD&C Blue 2 Indigocarmine 73015
FD&C Green 3 Fast Green FCF 42035
Caramel Burnt sugar
Titanium dioxide – 77891
Colorants are obtained in two forms dyes and lakes.
 Dyes are dissolved in the binding solution prior to the granulating process. However, during drying
their color may migrate to the surface and may produce mottling of the tablet.
 So another approach is to adsorb the dye on starch or calcium sulfate from its aqueous solution; the
resultant powder is dried and blended with other ingredients.
 Color lakes are dyes which are adsorbed onto a hydrous oxide of a heavy metal (like aluminium)
resulting in an insoluble form of the dye.
FLAVOURS AND SWEETENERS

Flavours are usually limited to chewable tablets or other tablets intended to dissolve in the
mouth.
Flavor oils are added to tablet granulations in solvents, are dispersed on clays and other
adsorbents or are emulsified in aqueous granulating agents (i.e. binder).
N.B. Usually, the maximum amount of oil that can be incorporated to a granulation without influencing its tableting
characteristics is 0.5 to 0.75% w/v.
The use of sweeteners is primarily limited to chewable tablets.
E.g. Sugar
Mannitol – 72% as sweet as sugar, cooling & mouth filling effect
Saccharin – Artificial sweetener
500 times sweeter than sucrose
Disadvantages (i) it has a bitter after taste
(ii) Carcinogenic
Cyclamate – either alone or with saccharin
– It is banned
Aspartame (Searle) – widely replacing saccharin
– Disadvantage – lack of stability in presence of moisture
MANUFACTURE OF TABLETS
Manufacture of tablets involves certain well defined steps: namely,
Pulverization and mixing Granulation Compression Coating (if required)
PULVERIZATION AND MIXING
In this step the different

solid / powder ingredients
are reduced to the same
particle size since particles
of different sizes will
segregate while mixing.

Instruments used for milling or size reduction:

General characteristics of various types of mills
Types of Mill Action used for Not used for
Cutter Cutting fibrous, crude animal friable material
and vegetable drugs
Revolving Action and impact fine grinding of soft material
abrasive materials
Hammer Impact almost all drugs abrasive materials
Roller Pressure soft material abrasive material
Attrition Attrition soft and fibrous abrasive material
material
Fluid energy mill attrition and impact moderately hard and soft and sticky material
friable material
For mixing dry powders following mixers are used:
GRANULATION
Objectives:
Simple powder may not have the desired flow property because there are may types of forces
acting between solid particles:
1. Frictional forces,
2. surface tension forces,
3. mechanical forces caused by interlocking of particles of irregular shapes
4. electrostatic forces and
5. Cohesive or van der Waals forces.
Though bulk density and shape of the particles are important but two of the most common experiments
done to get some idea about the flow property are
(i) Angle of repose and (ii) hopper flow rate measurement.
Values for angle of repose  300 usually indicate a free-flowing material and
Values of angle of repose  400 suggests a poorly flowing material.
Hopper flow rates have been used as a method to assess flowability of the powder mass. In this
method the flow of powder from a conical hopper is continually monitored by the flow of material out
of the hopper on to a recording balance device.
Question: “Mostly the materials, intended for compression into tablets are converted into
granules” – Why?
Ans: Materials intended for compaction into tablets must possess two characteristics:
(1) Fluidity and (2) compressibility.
Good flow properties are essential for the transport of the material through the hopper, into and through
the feed frame into the dies. Tablet materials should therefore be in a physical form that flows
uniformly and smoothly. The ideal physical form is sphere, since spheres offers minimum contact
surface between themselves and with the walls of the machine parts.
Unfortunately, most materials do not easily form spheres; however shapes approaching spheres
improve flowability. Hence flow properties of powder materials are improved by forming sphere like
regular shaped aggregates called granules.

WET GRANULATION
Step-I Milling of the drug and excipients
 Milling of the active ingredients, excipients etc. are milled to obtain a homogeneity in the final
granulation.
 If the drug is given in solution then during drying it will come up to the surface. To avoid this
problem drug is mixed with other excipients in fine state.
Step-II Weighing
 Weighing should be done in clean area with provision of air flow system.
 In the weighing area all the ingredients must not be brought at a time to avoid cross-contamination.
Step-III Mixing
Commonly used blenders are: (a) Double cone blender
(b) V – blender
(c) Ribbon blender
(d) Planetary mixer
Any one of the blender may be used to mix dry powder mass.
Step-IV Wet Massing
Wet granulation forms the granules by binding the powders together with an adhesive.
Binder solutions can be added in two methods:
Method-I Method-II
Drug + Diluent Drug + Diluent
Dry binder is added Binder Solution is added
Blended uniformly
Suitable solvent is added to activate the dry binder
Blended in a Sigma - mixer or Planetary mixer

till properly wet mass is formed
 The powder must be moist and not paste.

 Blending may take 30 mins to 1 hour.
N.B.
 To determine the proper moistening, the moist mass is balled in a palm, pressed by two fingers, if
fragments of granules are formed and not powder then the blending is stopped.
 Since, in general, the mass should be moist rather than wet or paste, there is a limit to the amount
of solvent that may be incorporated.
Therefore, when
(i) A small quantity of solvent is permissible, method-I is adopted and
(ii) A large quantity of solvent is required method-II is adopted.
 However, method-II will give more cohesiveness than method-I if the amount of binder remains
constant.
 If granulation is over-wetted, the granules will be hard, requiring considerable pressure to form the
tablets, and the resultant tablets may have a mottled appearance.
 If the powder mixture is not wetted sufficiently, the resulting granules will be too soft, breaking
down during lubrication and causing difficulty during compression.

Step-V Wet Screening

Wet screening process involves converting the moist mass into coarse, granular aggregates by
(i) Passage through a hand screen (in small scale production) or,
(ii) Passage through an oscillatory granulator of hammer mill equipped with screens having large
perforations (# 6 – 8 mesh screen).
Purpose (i) Increase particle contact point
(ii) Increase surface area to facilitate drying.
Step-VI Drying
 Drying is usually carried out at 600C. Depending on the thermolabile nature of the drug the
temperature can be optimized.
 Drying is required in all wet granulation procedures to remove the solvent, but is not dried
absolutely because it will pose problems later on. Hence, certain amount of moisture (1 – 4 %) is
left within the granules – known as the residual moisture.
Methods: Drying can be carried out
1. Tray dryers – it may take 24 hrs of drying
2. Truck dryers – the whole cabinet can be taken out of the dryer
3. Fluid-bed dryer – dried for 30 mins.
The total surface of the granules are dried uniformly but in tray dryer the lower surface of the granules
may not be dried uniformly. Case hardening may some time occur in tray dried products.
N.B. In case hardening the outer surface of the lumps of the wet powder will be dried quickly and become hard
(forming a hard crust), while the inner part will remain wet. This phenomenon is called case hardening.
Step-VII Dry Screening

After drying, the granule size is reduced by passing through smaller mesh screen.
 For drying granules the screen size to be selected depends on the diameters of the punch. The
following sizes are suggested:
Tablet diameter upto Mesh Size
3/16 ” # 20
3.5 / 16 – 5/16” # 16
5.5/16 – 6.5/16” # 14
7.0/16 or larger # 12
Step-VIII Lubrication of granules
 After dry granulation, the lubricant is added as a fine powder. It usually, is screened onto the
granulation through 60 or 100 mesh nylon cloth to eliminate small lumps as well as increase the
covering capacity of the lubricant.
 The lubricant is blended very gently using tumbling action to maintain the uniform granule size.
 Too much fine powder is not desirable because fine powder may not feed into the die uniformly
causing variation in weight and density.
 Since, the very nature of lubricant produce hydrophobic surface on the particle hence over blending
prevents the inter granule bonding that takes place during compression.
Example of wet granulation formulae:-

Ferrous sulfate tablets
Ingredients Quantity / tablet Remarks
Ferrous sulfate (dried) 300 mg Active ingredient
Corn Starch 60 mg Diluent
20% sugar solution q.s. Binder
Explotab 45 mg Disintegrant
Talc 30 mg Glidant & Antiadherent
Magnesium stearate 4 mg Lubricant

FeSO4 + Corn Starch

 Mix
 Moistened with sugar solution
 Passed through #12
Wet granules
 Dried on tray dryer (Temp: 60 – 650C, over night)
 Dry Screened through #18
Dry granules  Explotab + talc + Mg-stearate
 Compression
TABLET
DRY GRANULATION
Dry granulation is followed in situations where
(i) The effective dose of a drug is too high for direct compaction,
(ii) If the drug is sensitive to heat, moisture or both, which precludes wet granulation.
E.g. many aspirin and vitamin formulations are prepared for tableting by compression granulation.
Steps of granulations
Milling  Weighing  Screening  Blending  Slugging  Granulation (Dry)  Lubrication

Compaction
Slug:
Slug may described as poorly formed tablets or, may be described as compacted mass of powdered
material.
Purpose: To impart cohesiveness to the ingredients, so as to form tablets of desired properties.
Method: It is done either by (i) by high capacity heavy duty tablet press
(ii) Of by Chilsonator roller compactor.
(i) By high capacity tablet press large tablets are made because
(a) Fine powders flow better into large cavities, and
(b) Large slugs reduces production time
 The punches are flat faced
 Sufficient pressure should be applied.
 Powdered materials contains a considerable amount of air; under pressure this air is expelled and
fairly dense piece is formed. More time is allowed for this air to escape.
 The compressed slugs are comminuted in desired mesh screen.
 Lubricant is added twice : i.e.
1. During blending with other powders and
2. Added to the granulations
 The lubricant is blended gently with the granulation and is compressed into tablets
(ii) Chilsonator roller compactor

 Chilsonator consists of two grooved rollers. Powder is flowed into the grooves and compressed
mass is produced as the rollers rotates.
 Distance between two rollers can be adjusted.
 By the impeller always the air is removed from the powder mass.
 By using oscillatory granulator granules are prepared and lubricant is blended with the granules
and compressed into tablets.

Advantages of chilsonator over tablet press

1. Very high production rate
2. Pressure can be controlled
3. Lubrication is not required in the primary stage.
Using a tablet press Using a chilsonator
Powder + Lubricant Powders
 
Slugs Slugs
 
Granules Granules
 
Lubricated Lubricated
 
Compressed Compressed
Hence, in a chilsonator only once lubricant is used. Since lubricants, such as talc, magnesium stearate
etc. are hydrophobic in nature they will
(i) Impart problem in in-vitro disintegration
(ii) Compaction will not be efficient due to the decrease in inter-particular cohesive force.
Advantages of dry granulation over wet granulation

1. No application of moisture (required in wet granulation) and heat (for drying). So the drugs
susceptible to either moisture or heat or both can be made by dry granulation. E.g. calcium lactate
cannot be used by wet granulation. (Aspirin, Vitamin C)
2. Dry granulation involves less steps and hence less time is required than that of wet granulation.
3. Less steps requires less working space and energy.
Since popularity of wet granulation is more that dry granulation because former will meet all the
physical requirement for the compression of good tablets.
Example of dry granulation

Preparation of Aspirin tablets
Ingredients Quantity required per tablet Remarks
Aspirin (#20 mesh) 325.0 mg Active ingredient
Starch (dried) 32.5 mg Diluent / Disintegrant
Cab-o-sil 0.1 mg Lubricant
Method:
Aspirin + Starch + Cab-o-sil
10 mins  mixed in twin-shell blender for 10 mins
Powder blend
 Compressed into slugs of 1 inch diameter flat-face punch
Slugs
 Size reduction by Oscillatory granulator
Granulation (# 16 mesh)

Compressed
N.B. All operations are carried out in a dehumidified area at a relative humidity less than 30% at 700F
(21.10C).

DIRECT COMPRESSION
Steps:
Milling

Weighing

Sieving

Blending

Compression
Advantages: (i) It is much quicker than any of the previous process

(ii) Minimum number of steps are required.
Modified diluents, binders etc. are available in the market which assure spherical shape of the granules
to modify flow property. However, they are not used extensively.
1. If active medicament is less in amount then there will be no problem but in case of high dose large
amount of active ingredient is to be replaced by specially treated vehicles to improve flow property
or compressibility.
2. These specially treated materials are costly.
Example Vitamin B1 tablets

Ingredients Quantity for each tablet Remarks
Thiamine hydrochloride 100 mg Active ingredient
Avicel PH 102 83.35 mg Glidant
Lactose (anhydrous) 141.65 mg Diluent
Mg-stearate 6.65 mg Lubricant
Cab-o-sil 1.65 mg Lubricant
Method:
Vitamin B1 + Avicel + Lactose + Cab-o-sil

Mg-stearate + Mixture
 Mixed for 5 minutes
Compressed
N.B. Anhydrous lactose can be replaced with Fast Flo lactose which will reduce the requirement of
glidant (Avicel).
PROBLEMS FACED IN TABLETING
1. CAPPING AND LAMINATION

Capping is the partial or complete separation of the top or bottom crowns of a tablet from the
main body of the tablet.
Lamination is the separation of tablet into two or more distinct layers.
Usually these problems are apparent immediately after compression, or even hour or days later.
Detection: Subjecting tablets to the friability test is the quickest way to reveal such problems.
(a) Reason: Entrapment of excess air in the granules during compression. If the granules are light
and fluffy this type of problems are encountered frequently.
Remedies: Increasing the density of granules by adding more binder or changing the solvent of
binder.

(b) Reason: New set of punches and dies are very tightly fitted; i.e. the clearance is very negligible
hence air cannot come out.
Remedy: In that case punch diameter should be reduced by 0.005” (i.e. 5 thou)
(c) Reason: Granules should not be completely dried. If over dried or under dried then capping may
take place.
Remedy: So moisture content should be kept within 1 – 2%.
(d) Reason: Concave punches, used for longer period of time will form claw-shaped curve – this
forms capping.
Remedy: Punches are changed.
2. PICKING AND STICKING
Picking and sticking are the removal of surface materials from a tablet by sticking to the punch faces.
Picking: When some portion of the surface of the tablet is removed – it is termed as picking.
Cause: When punch tips have engraving or embossing, usually of letters B, A, O are difficult
to manufacture cleanly. These may produce picking.
Remedy: (i) Lettering should be designed as large as possible, particularly on punches of small
diameter.
(ii) Plating of the punch faces with chromium produces smooth, non-adherent face.
(iii) Colloidal Silica (Cab-o-sil) is added as polishing agent that makes the punch faces
smooth; so that material does not cling to them.
Sticking: Sticking refers to tablet materials adhering to the die wall.

Disadvantages:
1. When sticking occurs, additional force is required to overcome the friction between tablet
and the die wall during ejection.
2. Serious sticking at ejection can cause chipping of a tablet’s edges and can produce a rough
edge.
3. Also, a sticking problem does not allow the lower punches free movement and therefore
can place unusual stresses on the cam tracks and punch heads, resulting in their damage.
4. Sticking can also cause build-up of material on punch faces.
Causes:
1. Excessive moisture may be responsible for sticking.
Remedy: Further drying of the granulation is then required.
2. During compression heat is generated and
(a) Low m.p. lubricants e.g. stearic acid may produce sticking.
Remedy: Low melting point lubricant are replaced with high melting point lubricants
(e.g. Poly ethylene glycol)
(b) Low m.p. substances, either active ingredients or additives may soften sufficiently form the
heat of compression to cause sticking.
Remedies:
 Dilution of active ingredient with additional high m.p. diluents.
 Increase in the size of tablet.
 If a low m.p. medicament is present in high concentration then refrigeration of the
granules and then compressing may be the order.

3. MOTTLING
Mottling is an unequal distribution of color on a tablet, with light or dark patches in an
otherwise uniform surface.
Cause: Migration of water soluble dyes to the surface while drying.
Remedies:
 Change the solvent system.
 Change the binder system
 Reduce the drying temperature
 Grind to a smaller particle size.
 *** Use lakes instead of water soluble dyes.
QUALITY CONTROL OF COMPRESSED TABLET
Quality control of compressed tablet can be done by
(i) Official methods and
(ii) Unofficial methods.
1. WEIGHT VARIATION (Official)
This test is based on the fact that, if the weight variation is not much then it can be said that the
amount of medicament will not vary considerably. Conversely, if the weight variation is larger then it
can be concluded that the active medicament will also vary considerably.
Sources of weight variation
Weight variation is solely dependent on the poor flow property of granules and filling of die
cavity.
Poor flow properties arise from: (a) improper lubrication
(b) Size of granules
(c) Adjustment of lower punch.
Weight variation test
The U.S.P. weight variation test is run by weighing 20 tablets individually, calculating the
average weight, and comparing the individual tablet weights to the average. The tablets meet the USP
test if
“Not more than 2 tablets are outside the percentage limit and if
No tablet differs by more than 2 times the percentage limit.”
N.B.
Say 20 tablets weighed separately
Percentage limit is  10%.
Say the average weight was 100 mg.
Then the sample of tablets will pass the USP weight variation test if
18 tablets remain within 90 mg to 110 mg and
2 tablets remain within 80 mg to 120 mg.
The weight variation tolerance for uncoated tablets differ on average tablet weight.
Average weight of tablets (mg) Maximum percentage difference allowed

130 or less  10
130 to 324  7.5
More than 324 5
N.B. Weight of tablets: w1, w2, w3, wn.., w20.

Average weight of the tablets = w
So the weight variation of nth tablet =

 w  w  x 100%
n

2. CONTENT UNIFORMITY TEST
N.B. Weight variation test is applicable when the amount of medicament in the tablet is high. In potent drug
the medicament is less in amount in comparison to the other excipients. The weight variation may meet the
Pharmacopoeial limitation but this will not ensure the correct variation of potency. Hence, in this case the
weight variation test is followed by content uniformity test.
Content uniformity test

In this test 30 tablets are randomly selected for sample, and at least 10 of them are assayed
individually according to the official assay method.
Nine of the 10 tablets must have potency within  15 % of the labeled drug content. Only one
tablet may be within  25%.
If this conditions are not met then the tablets remaining from the 30 must be assayed
individually and none may fall outside  15% of the labeled content.
N.B. For example:

30 tablets are taken at random
10 tablets are assayed individually
In which 8 tablets remained within  15%
And 2 tablets remained within  15 % and  25 %.
So the test has to be carried out with rest of the 20 tablets.
And those 20 tablets must remain within  15%.
Conclusion: Out of the 30 tablets the potency of only 2 tablets may remain within 15 to 25 % rest of all the
tablets should remain within 15%.
3. TABLET HARDNESS
The resistance of the tablet to chipping, abrasion or breakage under conditions of storage,
transportation and handling before usage depends on its hardness.
Method:
A tablet is taken between the 2nd and 3rd finger and pressing it with the thumb as fulcrum. If
the tablet breaks with a “sharp snap”, yet, it does not break when it falls on the floor – is said to
possess proper hardness.
Instruments used:
1. Monsanto Hardness Tester
2. Strong Cobb Hardness Tester Manual mode of operation are more or less similar
3. Pfizer Hardness Tester
4. Schleuniger Apparatus – Operates without manual involvement.
Hardness of a tablet:
The hardness at which the tablet crushes is the hardness of the tablet.
Unit of hardness: Kg/sq.in. Or lb/ sq.in
Limit: Generally maximum 5 kg/sq.in. Hardness is required.
N.B.
 If the tablets are too hard then it may not meet tablet disintegration test.
 If the tablets are too soft then it may not with stand the handling, packaging and shipping
operations.
4. FRIABILITY
Tablet hardness is not an absolute indicator of strength since some formulations, when
compressed into very hard tablets may produce chipping, capping and lamination problems. Therefore
another measure of tablet strength i.e. friability is often measured, i.e. the friability.

Instrument: ROCHE FRIABILATOR 2 5 rp m

Objective of friability test: 4 m in s
This apparatus is designed to evaluate the ability of the
tablet to withstand abrasion, in handling, packaging and shipping
6"
operation.
Method:
Few tablets, previously weighed are taken in the plastic R o c h e F r ia b ila to r
chamber of the laboratory friability tester. In the plastic chamber the tablets are subjected to abrasion
and shock by rotating the plastic chamber at 25 rpm for 4 mins (i.e. total 100 revolutions). The tablets
are dusted and reweighed.
Limit
For conventional compressed tablet the weight loss should be within 0.5 to 1.0 %.
5. DISINTEGRATION TEST OF TABLETS (Official)

For most tablets, the first important step toward solution is breakdown of the tablet into smaller
particles or granules – this process is known as disintegration.
 The time a tablet takes to disintegrate is the disintegration time.
USP disintegration test apparatus
The USP device to test disintegration uses glass tubes with the following dimensions:
Number of tubes = 6
Length = 3 inches
Upper end open, lower end closed with #10 mesh screen.
To test the disintegration time one tablet is placed in each tube, and the basket rack assembly is
positioned in a 1-litre beaker of water, simulated gastric fluid or simulated intestinal fluid, at
370C20C, such that the tablet remain 2.5 cm from the bottom of the beaker.
A standard motor moves the basket up and down through a distance of 5 to 6 cm at a frequency
of 28 to 32 cpm (cycles per minute).
Perforated plastic discs may also be placed on top of the tablets to impart an abrasive action to
the tablets. They are useful for tablets that float.
 USP disintegration test will be passed if all the tablets disintegrate and the particles passed through
the #10 mesh screen within the specified time. If any residue remains, it must have a soft mass with
no palpable firm core.
 Disintegration time is suggested for 5 minutes for uncoated Aspirin tablets. Majority of the
uncoated tablets have maximum disintegration time (DT) of 30 minutes.
 Enteric coated tablets shows no evidence of disintegration after 1 hr in simulated gastric fluid. The
same tablets are then tested in simulated intestinal fluid and are to disintegrate in 2 hrs plus the time
specified in the monograph.
6. DISSOLUTION TEST
Why is it required?
1. Disintegration test simply identifies the time required for the tablet to break up under the condition
of the test but it does not ensure the drug release in the bulk of the fluid.
2. Rate of dissolution is directly related to the efficacy of the drug.
3. Rate of dissolution is a good index for comparing the bioavailability of two tablet products of the
same drug.
USP XX / NF XV, Supplement 3 specifies two apparatus for dissolution test.

1. Apparatus - I
In general, a single tablet is placed in a small wire mesh basket and immersed in the dissolution
medium (as specified in the monograph) contained in a 1000 ml flask at 370  0.50C. Generally it is
rotated at 50 rpm unless otherwise specified.

2. Apparatus 2
The same equipment is used. Instead of basket a paddle is introduced as the stirring element.
The tablet is allowed to sink at the bottom of the flask before stirring.
Limit: A value of t90% (i.e 90% drug release) within 30 minutes is often considered satisfactory and is
an excellent goal since a common dissolution tolerance in the USP/NF is not less than 75% dissolved in
45 minutes.
TABLET COATING
Reasons behind coating of tablets:
The reasons behind coating of tablets are as follows:
1. To mask the taste, odour or colour of the drug. Improving the product appearance, particularly
where there are visible differences in tablet core ingredients from batch to batch.
2. Provide physical protection, facilitates handling, particularly in high speed packaging / filling lines.
3. To provide chemical protection from its surrounding environment (particularly air, moisture and
light).
4. To control the release of drug from the tablet e.g. sustained release tablets, repeat action tablets.
5. To protect the drug from the gastric environment of the stomach with an acid resistant enteric
coating.
Tablet properties (or Core properties)

Tablets that are to be coated are called core. This core must possess the proper physical characteristics.
1. In pan coating process the core tablets roll in the pan or cascade in the air stream in air suspension
coating. To endure the intense attrition between tablets or wall of the pan the tablets must have
enough hardness.
2. Sugar coating can mask the imperfection on the surface but film coating cannot, hence, for film
coating the core surface must be smooth.
3. The tablets must be in constant motion during the early drying phase or tablet agglomeration may
occur. The ideal shape for coating is a sphere; the worst shape is a square flat-faced tablet and in
practice rounded, convex shaped tablet cores are taken.
4. For coating materials to adhere to the tablet the coating composition must wet the surface of the
core. E.g. hydrophobic tablet surfaces are difficult to coat with aqueous-based coating.
TABLET COATING PROCESSES

Two types of tablet coating are popular –
(i) Sugar coating and (ii) film coating.
SUGAR COATING OF COMPRESSED TABLETS

The sugar coating process can be subdivided into six main steps:
1. Sealing
2. Subcoating
3. Smoothing (Syruping)
4. Color coating
5. Polishing and
6. Printing
1. Sealing
Objectives (i) To prevent moisture penetration into the tablet core, a seal coat is applied.
(ii) To strengthen the tablet core without a seal coat, the over wetted tablets would
absorb excess moisture, leading to tablet softening, and may affect the physical and
chemical stability.

Ingredients  Alcoholic solutions of Shellac (10 – 30% solid) or

 alcoholic solution of zein,
 alcoholic solution of cellulose acetate phthalate (CAP) or
 Alcoholic solution of polyvinyl acetate phthalate.
N.B.
 With aging the disintegration and dissolution time is found to increase with shellac due to
polymerization
 Zein is an alcohol soluble protein derivative obtained from corn (maize).
2. Subcoating
Objectives To round the edges and build up the tablet size. Sugar coating can increase the tablet
weight by 50 to 100% at this step.
Method The subcoating step consists of alternately applying a sticky binder solution to the
tablets followed by a dusting of subcoating powders and then drying.
Subsequent coatings are applied in the same manner until the tablet edges have
been covered and the desired thickness is achieved.
Ingredients  Binder solution formulations for subcoating:-
Gelatin 3.3%(w/w)
Gum acacia (powder) 8.7%(w/w)
Sucrose 55.3%(w/w)
Water to 100%(w/w)
 Dusting powder formulation
Calcium carbonate 40.0%(w/w)
Titanium dioxide 5.0%(w/w)
Talc (asbestos free) 25.0%(w/w)
Sucrose powder 28.0%(w/w)
Gum acacia powder 2.0%(w/w)
3. Smoothing or syruping
Objectives To cover and fill in the imperfections in the tablet surface caused by the subcoating
step.
Ingredients Simple syrup solution (approximately 60 – 70 %( w/w)).
Often the smoothing syrups contain a low percentage of titanium dioxide (1 – 5%) as
an opacifier. This gives a very bright and reflective background for the subsequent
coloring step.
4. Colour coating
Objective To impart an elegant and uniform colour.
Ingredient Syrup (60 – 70% sucrose) containing the desired color.
Method Syrup solutions containing the dyes are coated upto 60 individual applications until the
desired color is achieved. After each application of color the coatings are dried.
In the finishing step a few clear coats of syrup may be applied.
5. Polishing
Objective To produce the desired luster on the surface of the tablet.
Ingredients Mixtures of waxes (like beeswax, carnauba wax, candella wax or hard paraffin).
Method Either this mixtures of waxes are applied as powder or as dispersions in various
organic solvents in a polishing pan (canvas line pan).

6. Printing
In order to identify sugar-coated tablets often it is necessary to print them, using
pharmaceutical grade ink, by means of a process of offset rotogravure.
FILM COATING
Film coating adds 2 to 5% to the tablet weight.
Film coating can be done by the following three methods.
(i) Pan-pour method:
Viscous coating materials are directly added from some container into the rotating pan moving
with the tablet bed. Tablets are subjected to alternate solution application, mixing and then drying.
Disadvantages:
 The method is relatively slow.
 It relies heavily on the skill of the operator.
 Tablets always require additional drying to remove the latent solvent.
 Aqueous film coating are not suitable for this method because localized over wetting will produce
physicochemical instability.
(ii) Pan-spray method:

Coating material is sprayed over the tablet bed from nozzles and hot air is passed through the
tablet bed to dry it.
The variables to be controlled is pan-spray film coating process are:
(a) Pan variables:
Uniform mixing is essential to deposit the same quantity of film on each tablet.
1. Pan design or baffling:
Some tablet shapes mixes freely while other shapes may require a specific baffling arrangement
to ensure adequate mixing.
Disadvantages: Baffles may produce chipping and breakage if not selected properly.
(b) Pan speed
Pan speed affects mixing and the velocity at which the tablet pass under the spray.
 Too slow speed cause localized over-wetting resulting in tablets sticking to each other or to the pan.
 Too high speeds may not allow enough time for drying before the same tablets are reintroduced to
the spray. This results in a rough coating appearance on the tablets.
 Optimum pan speed: 10 – 15 rpm for nonaqueous film coating
3 – 10 rpm for aqueous film coating.
(c) Spray variables
1. Rate of liquid application
2. Spray pattern
3. Degree of atomization
These three spray variables are interdependent.
For spraying two types of systems are there:
(a) High-pressure, airless system and
(b) Low-pressure, air atomization system.
 The proper rate of liquid application depends on the mixing and drying efficiency of the system and
the coating formula.
 A band of spray should be spread evenly over the tablet mass. In larger pans, more nozzles must be
added to cover the tablet bed width.
A spray pattern that is too wide will apply coating on the pan.
A spray pattern that is too narrow will produce localized over-wetting.
Spray width can be adjusted by moving the nozzles closer or further away from the tablet bed.
 Atomization is the process where by the liquid stream is finely subdivided into droplets. The degree
of atomization (i.e. the size and size-distribution of the droplets). Too fine atomization causes some
droplets to dry before reaching the tablet surface, resulting in roughness on the tablet surface and

excess dust in the pan. Too large atomization causes localized over-wetting – leads to sticking,
picking or a rough “orange peel” effect.
(d) Process air variables (temperature, volume, and rate) are required for optimum drying of the coating
by evaporation of the solvent.
The balance between the supply and exhaust air flow should be such that all the dust and
solvent are confined within the coating system.
(iii) Fluidized bed process (air suspension coating)

This process have been successfully used for rapid coating of tablets, granules and capsules.
Process variables are as follows:
(a) Chamber design and air flow rate controls the fluidization pattern.
(b) Tablet shape, size and density.
(c) Volume and rate of air flow
– Too high rate produce attrition and breakage of tablets
– Too low rate  mass does not move fast enough through the spray region  over-wetting occurs.
(d) Inlet and exhaust air temperature.
DEVELOPMENT OF FILM COATING

Before coating a tablet the coating formula is first cast on either a glass, Teflon or aluminium
foil surface. Glass is preferred for cast films. The coating is done by spreading with a glass rod. After
drying, the cast films are assessed for the following properties:
(i) Physical appearance – potential colorant or opaquant separation is noted.
(ii) Lack of color uniformity
(iii) Insoluble additives have been properly suspended or not.
(iv) Water vapor permeability
(v) Film tensile strength
MATERIAL USED FOR FILM COATING
Film formers
Nonenteric materials : e.g. Hydroxypropyl methylcellulose (HPMC)

Methylhydroxy ethyl cellulose (MHEC)
Ethylcellulose (EC)
Hydroxypropyl cellulose (HPC)
Polyvinyl pyrrolidone (PVP)
Sodium carboxymethyl cellulose (Sod. CMC)
Polyethylene glycols (PEG)
Acrylate polymers e.g. Eudragit E
Enteric materials: e.g. Cellulose acetate phthalate (CAP)

Acrylate polymers (Eudragit L, S)
Hydroxypropyl methylcellulose phthalate (HPMCP)
Polyvinyl acetate phthalate (PVAP)
Solvents
Criteria
1. It should either dissolve or disperse the polymer system.
2. It should easily disperse other coating solution components into the solvent system.
3. Small concentration of polymers (2 to 10%) should not result in an extremely viscous solution
system (> 300 cps), creating process problems.

4. It should be colorless, tasteless, odourless, inexpensive, non-toxic, inert and non-inflammable.

5. It should have no environmental impact.
Colorants: Same as tablet.
Opaquant extenders:
Very fine inorganic powders e.g.
Titanium dioxide (TiO2)
Silicates like talc, aluminium silicate
Carbonates like magnesium carbonate
Sulfates like calcium sulfate
Oxides like magnesium oxide and
Hydroxides like aluminium hydroxides.
Miscellaneous coating solution components

Flavors and sweeteners
Surfactants are used to solubilize immiscible or insoluble ingredients
Antioxidants
Antimicrobial agents.
FILM DEFECTS
Variations in formulation and processing conditions may result in unacceptable quality in the
film coating. Some of the problems are as follows:
Picking
Overwetting or excessive film tackiness or when the drying system is inefficient – tablets stick
to each other or to the coating pan. On drying, at the point of contact, a piece of the film may remain
adhered to the pan or to another tablet, giving a “picked” appearance to the tablet surface and resulting
in a small exposed area of the core tablet.
Remedy:
 A reduction in the liquid application rate or,
 Increase in the drying air temperature and air volume usually solve this problem.
 If excessive tackiness is there then the formulation is changed.
Roughness
A rough or gritty surface is a defect often observed when the coating is applied by spray. Some
of the droplets may dry too rapidly before reaching the tablet bed, resulting in droplets on the tablet of
“spray dried” particles instead of finely divided droplets of coating solution.
Roughness also increases with pigment concentration and polymer concentration.
Remedy
 Moving the nozzle closer to the tablet bed
 Reducing the viscosity of coating solution.
Bridging and filling

During drying, the film may shrink and pull away from the sharp corners of a bisect, resulting
in “bridging” of the surface depression.
This defect may be so severe that the monogram or the bisect is completely obscured.
This is a problem in the formulation.
Remedy
 Increasing the plasticizer amount in the formulation
 Changing the plasticizer can decrease the incidence of bridging.
Filling: If the solution is applied too fast, over-wetting may cause the liquid to quickly fill and be
retained in the monogram – this is called filling.

Remedy
 Judicious monitoring of the fluid application rate, and
 Thorough mixing of the tablets in the pan prevent filling.
Blistering
When coated tablets require further drying in ovens, too rapid evaporation of the solvent from
the core and the effect of high temperature on the strength, elasticity and adhesion of the film may result
in blistering.
Remedy Milder drying conditions are adopted.
Hazing / Dull film (Bloom)

It can occur when too high a processing temperature is used for a particular formulation. It is particularly
evident when cellulosic polymers are applied out of aqueous media at high processing temperatures.
It can also occur if the coated tablets are exposed to high humidity conditions and solution of film results.
Color variation
 Improper mixing, uneven spray pattern.
 Insufficient coating may result in color variation.
 The migration of soluble dyes, plasticizers, and other additives during drying may give the coating
a mottled or spotted appearance.
Remedy
 Use of lake instead of dye.
 Changing the plasticizer and additives.
Cracking
Cracking occurs if the internal stresses in the film exceed the tensile strength of the film. The
tensile strength of the film can be increased by using higher molecular weight polymers or polymer
blends.
Internal stresses in the film can be minimized by adjusting the plasticizer type and
concentration, and the pigment type and concentration.
Plasticizers
These are used to impart flexibility to the film.
e.g. Castor oil, propylene glycol, glycerin,
Polyethyleneglycol (PEG) 200 and 400,
Surfactants e.g. polysorbates (Tweens), Sorbitan esters (Spans) and organic esters.
1. Ques: Draw a sketch of the layout of a tablet manufacturing unit. Differentiate between capsule unit and this.

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 TABLETS
TABLETS DOSAGE FORM IMPORTANT POINTS FOR GPAT EXAM
 90% of drugs are in oral dosage form.

 Tablet is unit dosage form.
 Liquid dosage forms r given in dose of medication 5-30%.
 Tablet should have 2-4% of moisture.
EVALUATION
 GENERAL APPEARANCE
 Size and shape – compressed tablets shape and dimensions are determined by the tooling
during the compression process.
Rem-when compression force is constant, tablet thickness varies with changes in die fill,
with particle size distribution, packing of particle mix and tab. Weight.
When die fill is constant, thickness varies with variation in compressive load.
 Crown thickness of tablet measured by Micrometer.
 Total crown thickness is measured by Vernier calliper.
 Tablet thickness should be controlled with ±5% of std. Value.
 The more the convex the tablet surface more is the capping problem so one has to use
slower tablet machine or one with pre compression capabilities.
 Unique identification markings-given in Physicians’ Desk Reference (PDR).
 Product code is given from National Drug Code (NDC).
 Mottling-non uniformity of colour over tablet surface.
 For colour quantification 3 methods-reflectance spectrophotometry, tristimulus
colorimetry and micro-reflectance photometry.
 Hardness and Friability
 Hardness of tablet directly effects dissolution behaviour.
 It is the force req. to break the tablet in diametric compression test.
 Hardness also called crushing strength.
CONTACT AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 1

 Devices used
 Monsento tester (stockes tester)-easy to handle. Manually operated, gives strength in kgs.
 Strong-cobb tester-force applied by hydraulic pressure and later air pressure not manually.
It gives value 1.6 times higher than the original strength.
 It gives strength in kgs.
 Pfizer tester-same principle as pair of pliers.(kgs)
 Two testers to eliminate operation variations:-
1. Erweka tester-gives strength in Kgs.
2. Schleuniger tester-operates in horizontal position-gives strength in KGs and
Strong Cobb units.
 Hardness and thickness of tablet is a function of die fill and compression force.
 At constant compression force, hardness increase with increasing die fill.
 At constant die fill, hardness increase and thickness decrease when compression force is applied.
 Roche friabilator machine is used for measuring friability of tablet.
Tablets fall from-6 inch distance
Total RPM -25, Total revolutions – 100, Time - 4 minutes
Limits- 0.5-1.0% (USP), not more than 1% (IP).
 Effervescent tablets and chewable tablets show higher friability value than above so
stack packaging for them.
 Vickers test is used to measure the surface hardness.
 ‘Whiskering’ phenomenon is related with tablets with deeply concave surfaces or punches
used were in poor condition and such tablets have higher than normal friability values.
HARDNESS LIMITS
TABLET HARDNESS LIMIT
SOFT 2 KG
SUSTAINED RELEASE 8 KG
GENERAL 4 KG
HARD 6 KG
EFFERVESCENT 1.3 KG
STANDARD HARDNESS SHOULD BE MIN. 4 KG

Webster and Van Abbe tester-indicate edge damage during handling.

 WEIGHT VARIATION
 Total tablets taken-10.
 Limits -Tablets meet USP if not more than 2 tablets are outside the limit and no tablet
should differ by more than 2 times the original limit.
 This test is used if the tablet contains 90-95% API. It is not appropriate for low dose
containing tablets. API should be more than 50mg. (i.e-potency).
 For these content uniformity test is used.
USP LIMITS
AVERAGE WT OF TABLETS(MG) MAX. % DIFF. ALLOWED
130 or less 10
130-324 7.5
More than 324 5
I.P LIMITS
AVERAGE WT OF TABLETS (MG) MAX. % DIFF. ALLOWED
80 or less 10
80-250 7.5
More than 250 5
 CONTENT UNIFORMITY TEST:

 It should be between 95-105%.
 Tablet potency for this test should be less than 50mg.
 For digitoxin it is 90-110%.
 If larger wt. Variation, no good content uniformity.
Test:
 Total tablets-30
 Total assayed-at least 10
 9 of the tablets should contain 85-115% API.
 10th tablet may contain 75-125% API. Test passed
 If above conditions not met other 20 tablets should be assayed, and no one should
fall outside 85-115% range.

 DISINTEGRATION
APPARATUS
 6 test tubes
 Mesh size: 10 mesh i.e 1.7mm (USP), 8 mesh i.e 2mm (IP)
 Glass tubes are 3 inches long
 Beaker contains 1L of water, simulated gastric fluid or simulated intestinal fluid.
 Temperature: 37±2 degree Celsius. (Remember with reference to difference with dissolution)
 Tablets remain 2.5 cm below surface of liquid on upward movement and vice versa.
 No. of cycles per minute: 28-32
IP LIMITS
Tablet/Capsule Liquid Disintegration time(min)
Uncoated tablet Water 15 min (USP-30 min)
Sugar coated Water 60 min

2 hr in gastric fluid media and
0.1N HCl with phosphate
Enteric coated 1 hr in intestinal fluid(USP it
buffer
is reverse)
Film coated Water or 0.1N HCl 30 min
Vaginal tablets Water 30 min

Soluble, dispersible and Water
3 min
effervescent tablets (19-21 deg. Celcius)
Hard gelatin capsules Water 15 min
Soft gelatin capsules Water 60 min
 DISSOLUTION
USP
Apparatus 1-Basket type
Mesh screen-10 mesh (USP)
Temperature: 37±0.5 degree Celsius. 900 ml flask.
Apparatus 2-paddle type
900 ml. Flask.
Contains wire helix to prevent tablet from floating.

Limits (USP)
 Not less than 75% should be dissolved in 45 min.
 90% of the drug should be dissolved in 30 min.(this is not USP limit, it is industrial limit)
 Above both values are Q values.
 Dissolution acceptance criteria(IP)
Stage No. Of dosage Acceptance criteria
units tested
S1 6 No dosage unit is less than Q+5%.
S2 6 Average of 12 dosage units is equal to or not more than Q% and no
unit is less than Q-15%.
S3 12 Average of 24 dosage units is equal to greater than Q% and not
more than 2 dosage units are less than Q-15% and no dosage unit is
less than Q-25%.
TABLET COMPRESSION APPARATUS

 Dies define shape and size of tablet.
 Cam tracks guide the movement of punches.
 Multi-station presses are called rotary presses.
 Turrets-the portion of the head that hold the upper and lower punches.
 Fette machines-they chill the compression components to allow compression of low
melting solids such as waxes use (in case of suppositories0.
TOOLING
 BB tooling-most commonly used.length-5.25 inch,
 Nominal barrel diameter-0.75 inch, 1 inch head diameter.
 B tooling-5.25 inch, nominal barrel diameter-3 9/16 inch, 1 inch head diameter.
 D tooling-used for larger tablets. 5.25 inch,
 Nominal barrel diameter-1 inch, 1.25 inch head diameter.
 Dwell time-time for which tablet remains under compression.
 Remember-Devices which measure compression force at each compression station.
 Pharmakontroll,
 Killiani Control System,
 Thomas Tablet Sentine

 PROCESSING PROBLEMS IN TABLET

1) Capping and lamination-capping is partial or complete separation of top or bottom parts
of tablet from main body of tablet.
Lamination is separation of tablet into 2 or more distinct layers. It is due to:-
 Deformational properties of formulation i.e plastic deformation
 Deep concave punches.
 Absence of adequate moisture.
 Tablet tooling
 Incorrect setting of press.
2) Picking and sticking- Picking occurs due to engraving and embossing.
In sticking tablet material sticks to die wall.
3) Mottling- uneven distribution of color on tablet.
4) Weight Variation
5) Poor flow- Talc or colloidal silica helps in improving the flow.
Poor flow can result in bridging, arching and rat holling.
6) Poor mixing
7) Punch variation
8) Hardness variation
9) Double impression
 TABLET GRANULATION
 It improves flow properties of tablet.
 Shape factor of granule should be 6 just like sphere for good flow.
 The method used for measurement of surface area solid granules or particles are air
permeability method and gas-adsorption method (He gas is used).
 Dense granules require higher compression force to form cohesive compact and they are less
friable.
 For determining granule density-Mercury displacement method is used.
 Other method uses benzene as organic solvent.
 As granule size increase bulk density decreases.
 As particle becomes more spherical bulk density increases.
 The strength of tablet is mainly due to surface tension of liquid and capillary forces.
 For measuring granule strength and friability ASTM (American Society for Testing
Materials) specification is taken into account and compression strength are taken into account.

 TYPES OF GRANULATION
 DRY GRANULATION
 Also called compression granulation.
 Used when drug is sensitive to moisture.
 Slugs are formed in this.so process also called slugging.
 Roller compactor instrument is used. Can produce 500 kg of slugs.
 Main advantage is that no need to use excess lubricants.
 WET GRANULATION
 Granules formed by adhesive forces.
 Surface tension forces and capillary pressure are initially responsible for wet granulation.
 Solvents are used considering EPA (Environmental Protection Agency) regulations.
EQUIPMENTS FOR WET GRANULATION

1. Littleford Lodige mixer- Capable of both wet massing and blending.
 Time taken-30-60 sec.
 Horizontal in operation.
 Temperature rise of 10-15 deg. is expected.
2. Diosna mixer or granulator- contains bowl in vertical position.
 Total time 11-12 min.
3. Littleford MGT mixer- vertical in operation.
4. Gral mixer- Modification of planetary mixer (IMP).
 DIRECT COMPRESSION
 Eg. NaCl, KCl can be directly compressed.
 Uses directly compressible diluents like spray dried lactose.
 They have good flow and compressibility.
 Maximum of 30% of API is used in direct compression tablet.
 TABLET INGREDIENTS
 DILUENTS:
 Used to increase bulk of tablet.
 5-80% can be used.

 All the sugar containing diluents have tendency to undergo reaction with drugs containing –
NH2 group. This is called Maillard reaction which only changes color not content.
STARCH
 11-14% moisture present
 Dried starch has 2-4% moisture.
 Their moisture level increase to 6-8% following moisture exposure.
 Two types:
1) Directly compressible starch (Sta-Rx 1500)-used as diluents, binder and disintegrant.
Contains 10% of moisture.
2) Hydrolysed starch (Emdex, Cellutab: contain 90-92% dextrose and 3-5% maltose)-
directly compressible. Used in chewing tablets and have 8-10% of moisture.
LACTOSE
Three types of lactose.
1) Alfa-lactose monohydrate - Crystalline nature, has 5% moisture, poor flow and
compressibility and used in wet granulation. It gives Maillard reaction.
2) Spray dried lactose - <3% moisture. Good flow and compressibility. Used in direct
compression.it gives Maillard reaction. (In Maillard reaction furfuraldehyde is formed).
3) B-lactose (anhydrous) - hygroscopic. Used in direct compression and does not gives
Maillard reaction.
DEXTROSE
 Also called cerelose.
 Can be used instead of lactose.
MANNITOL
 Used in chewable tablet due to negative heat of solution.
 Non-hygroscopic.
 Non-cariogenic.
 Used in vitamin formulations.
SORBITOL
 Optical isomer of mannitol.
 Hygroscopic.

SUCROSE
Available as co-processed form such as
SUGARTAB (90-95% sucrose + 7-10% invert sugar),
DIPAC (97%sucrose + 3% modified dextrin)
NUTAB (95%sucrose + 4% invert sugar + Mg. stearate + corn starch).
Used in direct compression.
Hygsroscopic
Important point-Kaolin and bentonite, diluents, is not used with cardiac glycoside, synthetic
estrogens and alkaloids.
MICROCRYSTALLINE CELLULOSE (MCC)

 Trade name- AVICEL
 DIRECTLY COMPRESSIBLE
 Two grades: PH 101(powder) and PH 102(granules)
 Also act as disintegrating agent.
 Hygroscopic in nature.
 May delay the release of drug.
DICALCIUM PHOSPHATE (DCP)

 Non-hygroscopic (Just like mannitol)
 Moisture sensitive drugs can be used with it
 Not used with tetracycline due to complex formation.
CLASSIFICATION IN OTHER WAY

 Wet granulating diluents- alfa lactose, kaolin, bentonite, dicalcium sulphate
 Direct compression- Spray dried lactose, colloidal silica, NaCl and NaHCO3 for
dental cones, direct com. starch.
 Binders and adhesives
Used to provide cohesive qualities.
More the binder, harder is the tablet.
NATURAL GUM
 Acacia and tragacanth are examples
 Used in 10-25%

GELATIN
 Natural protein
 10-20% in solution form.
 Upon storage disintegration time will increase with the use of such binders Starch
 10-20%solution.
 Give translucent paste.
 It undergoes hydrolysis to dextrin and glucose.
 Liquid glucose is 50%solution in water.
Modified natural polymers
 Methylcellulose (alcohol soluble, more soluble in cold water than hot water)
 Hydroxy propylcellulose HPC (alcohol sol.)
 Hydroxy propyl methylcellulose HPMC (water soluble)
 Ethylcellulose EC (alcohol soluble, retard D.T)
 PVP (polyvinyl pyrrolidone) used in 2%.used in aqueous and alcoholic solution.
 IPA (isopropyl alcohol)-widely used binder.
 ANOTHER CLASSIFICATION
 Solution binders- Starch, Sucrose, Gelatine, Acacia, Tragacanth.
 Dry binders- HPMC. Cross linked PVP.
 LUBRICANTS
 Decrease friction between diewall and tablet surface
 Can be used intragranularly (PEG, Vegetable oils) and extragranularly (talc, stearates).
 They are hydrophobic in nature.
 Fluid lubricant-liq. Paraffin
 Boundary lubricant-stearic acid
 What is bolting of lubricant?

Lubricant is passed through 60-100 mesh nylon cloth in order to get fine particles this is
called bolting of lubricant.
 Hydrocarbon/mineral oil
 Applied as fine spray.
 Mostly used for aspirin tablets

 Calcium and Mg. Stearate

 used in 1%
 may cause delay release
 Mg.stearate is used with SLS due to its hydrophobic property.
 It is not used with acidic drugs
 COMPRITOL 888
 It is glyceryl monoester of behenic acid.
 Water soluble lubricants
 Sodium Benzoate, sodium acetate, NaCl, leucine, PEG etc.
 GLIDANTS
1) TALC
 Used in 5%.
 Can also be used as anti-adherent.
 Contains traces of iron so may act as catalyst for the drugs which are degraded by Fe.
 Also contain calcium so not used with tetracycline.
2) COLLOIDAL SILICA
Available in 3 forms
1. Cab-o-sil (<1%)
2. Aerosil (0.25-3%)
3. Syloid.
3) CORN STARCH
 Use in 5-10%
DISINTEGRANTS
 Facilitate breaking up of tablet Act by 3 mechanism

1. By swelling - Alginate, starch dye, PVP
2. By wetting - SLS, Clay, Bentonite
3. Effervescent - NaHCO3 and citric acid

EXAMPLES
STARCH
 5-20%
 Modified starches are used which are: Primogel and Explotab.
 they are low substituted carboxymethyl starches.(1-8% used, but 4%is optimum)
 CLAYS
 Veegum (Mg. Aluminium silicate) (10%)
 Bentonite (10%)
 both are used only for colored tablets
 They are most effective in sulfathiazole tablets.
 SUPER DISINTEGRANTS
 They are used in lower concentration. of 2 % to 6 %,
 while traditional disintegrants such as starches often require concentrations of about 20 %.
Sodium Starch Glycolate Sodium Carboxymethyl Starch
Croscarmellose Sodium Soy Polysaccharides
 Primojel®, sodium starch glycolate, and Primellose®, croscarmellose sodium, which show
outstanding disintegration characteristics for tablets prepared by direct compression, wet
granulation and for capsule formulations.
COLORING AGENTS
 Lake are the dyes that have absorbed on hydrous oxide
 As coloring concentration increases, mottling increases.
 To improve photosensitivity of dye use of UV absorbing chemical such as
benzophenone can be used.
 DI-PACLINE is a commercially available directly compressible sugar.

SWEETENERS
 Used in (0.5-0.75%)
 Cyclamates can be used.
 Cyclamates is 70 times sweeter than sugar. But are carcinogenic
 Aspartate (phenyl ester of methylacetic acid).
 Aspartam180-200 times sweeter than sugar and non-carcinogenic.
 Saccharin is carcinogenic and 500 times sweeter than sugar.
 Mannitol is used in chewable tablets and 72 times sweeter than sugar.
SOME INSTRUMENTS
MIXING
 For large qt. Of powder-twin-
 Shell blender
 Double-cone blender,
 Planetary mixer.
 For continuous production
 Ribbon blender
 Rotocabe-blender
 Mass mixer
 Sigma blade mixer
 High speed granulators
 Diosna mixer,
 Littleford MGT,
 Gral mixer
 For continuous production extruders are used E.g. Reitz extruders
 Topo granulators to prepare granules under high vaccum.
 Spheronization refers to formation of spherical particle from wet granulation.
 Marumerizer and CF-granlator are used for Spheronization.
 SPRAY CONGEALING/SPRAY CHILLING

 It is the process consist of melting solid and reducing them to beads or powders by
spraying molten feed into stream of colder air or gases.
 Monoglycerides are spray congealed at 50 deg F
 Carbohydrates are spray congealed at 167 deg F

 IMPORTANT INFORMATION
 Versa press is used for the preparation of layered tablets.
 Manestey dry cota instrument is used.
 Implantation tablets should have size of less than 8mm.
 Kern-injector-contain hollow needle and plunger.
 It is used for administration of rod shaped tablet.
 For sub-lingual and vaginl tablets, lactose is used as diluent.

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 SOLID DOSAGE FORM CAPSULE
CAPSULES
Syllabus:
Principles, materials and equipment involved in the formulation and filling of hard gelatin capsules and their
quality requirements, layout of capsule section. Account of soft gelatin capsules.
DEFINITION
Capsules are solid dosage forms in which the drug substance is enclosed in either a hard or soft, soluble
container or shell of a suitable form of gelatin.
Advantages of capsule dosage forms

1. They obscure the taste and odour of unpleasant drugs.
2. They are attractive in appearance.
3. They are slippery when moist and, hence, easy to swallow with a draught of water.
4. If properly stored, the shells contain 12-15% of moisture which gives flexibility and, consequently very
considerable resistance to mechanical stresses (cf. cachets).
5. Less adjuncts are necessary than tablets.
6. The contents are usually in fine powder which combined with adjuncts, provides rapid and uniform release of
medicament in the GIT.
7. The shells can be opacified with TiO2 or coloured to give protection from light.
8. The shells are physiologically inert and easily and quickly digested in the GIT.
9. Presentation of a drug in capsules, rather than in tablets, allows quicker submission of a new drug for clinical
trials, because fewer development problems are involved. Also it is easier to vary the dose.
Disadvantages of capsule dosage forms
1. Capsules are not used for administering extremely soluble materials such as potassium chloride, potassium
bromide, or ammonium chloride since sudden release of such compounds in the stomach could result in
irritation.
2. Capsules should not be used for highly efflorescent or deliquescent materials.
 Efflorescent materials may cause the capsules to soften.
 Deliquescent materials may dry the capsule shell to excessive brittleness.
MATERIALS
Capsules are made principally of gelatin blends and may contain small amounts of certified dyes, opaquing
agents, plasticizers and preservatives.
To modify the solubility of the capsules (e.g. to impart enteric property) methyl cellulose, polyvinyl alcohols and
denatured gelatin are used.

GELATIN
 Gelatin is a heterogeneous product derived by irreversible hydrolytic extraction of treated animal collagen
(obtained from animal skin and bone).
 Common sources of collagen are animal bones, hide portions, and frozen pork skin.
 There are mainly two types of gelatin commercially available:
Type A: Gelatin is derived mainly from pork skin by acid treatment. This gelatin has an isoelectric point in
the region of pH 9.
Type B: Gelatin is derived from bones and animal skins by alkaline processing (pH 4  5).
B Dry bone  5% HCl  Lime 10%  Lime  pH
10 - 15 days 4-8 weeks removal adjustment
B Calf skin  wash  Lime 10%  Water wash
6-12 weeks
A Pork skin  wash  Acid 1-5% HCL Acid removal
10-30hrs
Hot water  Filter  Vacuum  Cool to  Air dry  Mill

Extraction concentration solidify to size.
Blends of Gelatin A and Gelatin B are used.
 Bone gelatin produces a tough, firm film, but tends to be hazy and brittle.
 Pork skin gelatin contributes plasticity and clarity to the blend, hence bone gelatin and pork skin gelatin are
generally used in blends.
Method of production of empty hard gelatin capsule shells

1. Hundred and fifty (150) pairs of stainless mold pins (on which capsule is formed) are dipped into a gelatin
sol (melted gelatin) of carefully controlled viscosity to form the caps and bodies simultaneously.
2. The pins are usually rotated to distribute the gelatin uniformly during which time the gelatin may be set or
gelled by a blast of cool air.
3. The pins are moved through a series of controlled air drying kilns for the gradually and precontrolled removal
of water.
4. The capsules are stripped from the pins by bronze jaws and trimmed to length by stationary knives while the
capsule halves are being spun in chucks or collets.
5. After being trimmed to exact length, the cap and body sections are joined and ejected from the machine.
The entire cycle of the machine lasts approximately 45 minutes.

CAPSULE SHAPE
1. Simple telescoping hard gelatin capsules Body moves easily inside the cap
Disadvantages
(a) Body can come out of the cap easily spilling over the powder inside.
(b) In high speed capsule filling machines capsules may split and/or denting of the
capsule shell may occur.
2. Gelatin seal fuses the two capsule halves to create a one-piece capsule that is
tamper proof.
3. in the body:-
(a) Tapered rim is provided to prevent splitting / denting.
(b) Grooves which interlock the two halves together once the capsule has been
filled.
(c) Indentations to prevent premature opening.
CAPSULE SIZE
Empty gelatin capsules are manufactured in various sizes, varying in
length, in diameter, and capacity.
Their capacities vary with the bulk-density of the contents and the
pressure applied during filling.
For human use, empty capsules ranging in size from 000, the largest, to
5, the smallest are commercially available.
CAPSULE NUMBER AND VOLUME FILL IN IT
Capsule No. 000 00 0 1 2 3 4 5
Approx. Vol
1.50 0.90 0.75 0.55 0.40 0.30 0.25 0.15
(ml)

CAPSULE FILLING EQUIPMENT
There are several equipment available in the market but they may be classified into two classes depending on the
mode of operation.
 Lily, Parke-Davis, Höfliger and Karg, Osaka and Perry
 Zanasi, Macofar, Farmatic and mG2 equipment
LILY TYPE CAPSULE FILLING EQUIPMENT

Number of operators required = 1
Number of capsule output = 200,000 capsules / day
(a) The empty capsules are fed from the storage
hopper (1) and through the rectifying unit (2), into
the two-piece filling ring (3A and 3B).
Rectification is based on dimensional differences
between the outside diameters of the cap and body
portions of the capsule.
(b) As the ring (3A and 3B) is rotated, a vacuum is applied on its underside. The vacuum sucks the bodies into
the lower half of the ring, while the caps are retained in the upper portion. The two pieces of the ring are
separated, and the cap-containing portion is placed aside.
(c) The body containing portion of the ring is placed on a variable speed turntable and is mechanically rotated
under the powder hopper (4), which contains an auger for the forced delivery of the powder.
(d) After one (or more) complete rotations of the rings, the powder hopper (4) is removed, and the two segments
of the ring (3A and 3B) are rejoined.
(e) The intact ring is positioned in front of the peg ring (5) and the closing plate (6) is pivoted to a positioned
approximately 1800 from the position showed in the figure. Pneumatic pressure is applied to the peg ring (5),
which forces the caps in position.
(f) After opening the closing plate 96) the capsules are ejected through the portion of the ring by giving slight
hand pressure against the peg ring.
(g) The filled capsules are collected through the chute (7) into a collection chamber.
 Highest turntable speed: minimum total fill weights
Maximum weight variation
 Lowest turntable speed: maximum total fill weights
Minimum weight variation

ZANASI CAPSULE FILLING MACHINE
 No. of operators required = 0 (automatic)
 No. of capsules output = 4000 to 150,000 capsules / hr.
 In this type of equipment the empty capsule shells come down from hopper through individual tubes and
rectified. The capsule shells are seated in a holder with the body downward. Vacuum assists its
placement.
 Another vacuum is applied over the top of the holder to separate the cap from the body of the capsule.
 The cap containing half is moved aside. The lower part of the holder is exposed for filling.
 The powder is continuously mixed within the powder hopper and is maintained at a constant level prior
to change.
 A set of volumetric dosing nozzles, each of which picks up the product from the constant level container,
first compressing and then ejecting the powder into the capsule bodies.
 The cap holder half is repositioned over the block and closing is accompanied by both upper and lower
closing pins.
 Ejection is accomplished by compressed air.
PREPARATION OF FILLED HARD GELATIN CAPSULES
The preparation of filled hard gelatin capsules may be divided into the following steps.
1. Developing and preparing the formulation and selecting the size of the capsule.
2. Filling the capsules shells.
3. Cleaning and polishing the filled capsules.
CAPSULE FORMULATION
In developing a capsule formulation, the goal is to prepare a formulation that results in accurate dosage, good
bioavailability characteristics, and ease of capsule filling during production.
(a) To achieve uniform drug distribution throughout the powder mix the density and particle size of the
drug and excipients should be similar.
If required the particle size may be reduced by milling.
Then the drug and excipients are blended thoroughly to get a uniform powder mix.
(b) The powder mix must provide the type of flow characteristics required by the equipment.
 In case of Lily type equipment powder must be free flowing e.g. with acetyl salicylic acid flowable corn
starch is used.
 In case of Zanasi type equipment powder must have sufficient cohesiveness to retain its slug form during
delivery to the capsules. E.g. with acetyl salicylic acid compactible excipients such microcrystalline cellulose
are required.
 Lubricant such as, magnesium stearate can be used in Lily type and binders like mineral oil can be used in
Zanasi type capsule filling equipments.

(c) Selection of capsule size.
(i) When the dose of the drug is large and the diluent is not required or negligible in quantity, the size may be
selected after the development and preparation of the formulation.
(ii) When the capsule is meant for young or elderly patients the capsule size (smaller size) is selected first and
then formulation is prepared. If required the dose may be divided into two capsules.
(iii) A properly filled capsule should have its body filled with the drug mixture and its cap fully extended down
the body  a capsule size should be selected to meet this requirement.
FILLING THE CAPSULE SHELLS
(a) Manual punch method
For filling a small number of capsules in a dispensary pharmacists generally use punch method.
 Precise number of empty hard gelatin capsule shells are taken.
 The powder is taken on a clean sheet of paper or glass or porcelain plate. With a spatula a cake is formed
with the powder having a height of approximately 1/4 to 1/3 the length of the capsule body.
 Then the empty capsule body is held between thumb and forefinger and “punched” vertically into the powder
cake repeatedly until filled. The capsule bodies are capped.
 After capping the capsules are weighed to ensure accurate filling.
(b) Filling can be done by hand-operated capsule filling machine, Lily and Zanasi type capsule filling machines.
Lily is semi-automatic and Zanasi is fully automatic.
[For details see the equipment - how they are filled]
CAPSULE SEALING
To make the capsules “tamper evident” (previously the term was “tamper resistant”) two types of sealing
processes are there
(i) Banding: The two capsule parts are sealed with a gelatin or polymer band at the seam of the cap and body.
(ii) The contact areas of the cap and body are wetted with a mixture of water and ethanol and then thermally
bonded at 40 to 450C.
Capsule sealing equipment may be linked with capsule filling equipment to maintain production levels of
upto 150,000 capsules per hour per unit.
CLEANING AND POLISHING

After filling some powder formulation may adhere to the outside of the capsules. This powder
 may be bitter or unpalatable,
 May reduce the appearance of the capsule.
Methods of cleaning
1. Pan polishing: The Accela-Cota tablet coating pan may be used to clean and polish capsules. A polyurethane
or cheese cloth liner is placed in the pan, and the liner is used to trap the removed dust as well as to impart a
gloss to the capsules.

2. Cloth dusting: In this method, the bulk filled capsules are rubbed with a cloth that may not be impregnated
with an inert oil. Though it is a hand operation but by this method
(a) large volume of capsules can be polished,
(b) Powders too resistant to remove by other methods can be removed easily by this method.
(c) It imparts a somewhat improved gloss to the capsules.
3. Brushing: In this procedure, capsules are fed under rotating soft brushes, which serve to remove the dust from
the capsule shell. This operation is accompanied by a vacuum for dust removal.
e.g. ROTOSORT it removes loose powder,
Removes unfilled joined capsules
Removes capsules with loose caps
Erweka KEA  dedusting and polishing
Scidenader PM60  for cleaning and polishing
SOFT GELATIN CAPSULES

Advantages of soft gelatin capsules:
(i) Soft gelatin capsules are useful when it is desirable to seal the medication within the capsule.
(ii) The capsules are especially important to contain liquid drugs or drug solutions.
(iii) Also, volatile drug substances or drug materials especially susceptible to deterioration in the presence of air
may be better suited to a soft gelatin capsule than hard gelatin capsules.
(iv) Soft gelatin capsules are elegant and are easily swallowed by the patients.
CAPSULE SIZES AND SHAPES
Shape Diagram Size range (number represents the nominal capacity in
minims (1 cc = 16.23 minim)
Round 1,2,3,4,5,6,7,9,28,40,90,
40T,80T
Oval 1,2,3,4,5,6,7.5,10,.12,16,20,30,40,60,80,85,110.
3,4,5,6,8,9.5,11,14,16,20,90,360
Oblong
55,65,90,160,250,320,480
Tube

MATERIALS
The capsule shell is basically composed of gelatin, a plasticizer and water. It may contain additional ingredients
such as preservatives, coloring and opacifying agents, flavours, sugars, acids and medicaments to achieve desired
effects.
GELATIN
The gelatin should be of USP grade and it should have some additional specifications, namely, bloom strength,
viscosity and iron content of the gelatin used.
Bloom or gel strength
It is a measure of the cohesive strength of the cross-linking that occurs between gelatin molecules and is
proportional to the molecular weight of the gelatin.
Determination
6 2/3 % gelatin gel kept at 100C for 17 hours
A plastic plunger having diameter 0.5 inch.
Bloom strength = the weight (in gram) required to move the plastic
plunger in the Gelatin mass upto 4 mm.
 Normally for soft-gelatin capsules the bloom strength of gelatin required
ranges from 150 to 250 g.
In general with all the other factors being equal, the higher the Bloom
strength of the gelatin used, the more physically stable is the capsule shell.
 Cost is, in general, proportional to Bloom strength; hence, higher Bloom
strength gelatins are only used when necessary to improve the physical stability of the product or large
capsules (over 50 minims).
Viscosity of gelatin
Viscosity of a 6 2/3 % gelatin in water solution at 600C is a measure of the molecular chain length and
determines the manufacturing characteristics of the gelatin film.
General range of viscosity 25 to 45 mill poise, it may be within narrow range 38  2 millipoise.
Iron content
Iron is always present in new gelatin, and its concentration usually depends on the iron content of the
large quantities of water used in its manufacture.
Limit: Gelatin used for soft gelatin capsules should not contain more than 15 ppm of iron.
Disadvantages:
(i) Iron may react with the certified dyes.
(ii) It may react with organic compounds to produce color (e.g. with phenolic compounds).

PLASTICISERS
Very few plasticisers are used for soft gelatin capsules
(i) Glycerin USP
(ii) Sorbitol USP or
(iii) A combination of glycerin and sorbitol
The ration by weight of dry plasticiser: dry gelatin determines the ‘hardness’ of the gelatin shell.
TYPICAL SHELL HARDNESS AND THEIR USES.
Hardness Ratio of Dry glycerin / Usage

Dry gelatin
Hard 0.4 / 1 Oral, oil-based, or shell-softening products and those
destined primarily for hot humid areas. Oral, tube, vaginal
Oil-base, water-miscible-base, or shell hardening products

Medium 0.6 / 1 and those destined for temperate areas (hot & humid areas)
Tube, vaginal
Water-miscible base or shell hardening products and those

Soft 0.8 / 1 destined primarily for cold, dry areas.
ADDITIONAL COMPONENTS OF THE GELATIN MASS
Ingredients Concentration Purpose
Category-I
Methyl paraben 0.2 % Preservative
Propyl paraben (4 : 1) q.s.
FD&C and D&C water-soluble dyes, 0.2 to 1.2 %

certified lakes, pigments, vegetable 0.1 % Colorants
colours
Titanium di-oxide 2% Opacifier

Ethyl vanillin, Essential oils Flavor
Category-II To produce chewable shell and taste

Sugar (sucrose) to 5 % Aids solubility reduces aldehydic
Fumaric acid to 1 % tanning of gelatin

NATURE OF THE CAPSULE CONTENT

Soft gelatin capsules can be used to dispense a variety of liquids, Solids, Combination of miscible liquids,
Suspension of solids in liquids.
Selection of capsule size
The maximum capsules size and shape for convenient oral use in humans is the 20 minims oblong, 16 minims
oval or 9 minims round
Types of liquids for encapsulation in soft gelatin capsules
1. Water, ethanol, and emulsion  these are water miscible or volatile components and they cannot be included
as major constituents of capsule since they can migrate into the hydrophilic gelatin shell and volatile from the
surface.
2. Gelatin plasticizers like glycerin, propylene glycol cannot be major constituents of capsules owing to their
softening effect on the gelatin shell.
3. Upto 10% glycerin and / or propylene glycol can be used as co-solvents with PEG or other liquids that have a
shell-hardening effect when capsulated alone.
Most widely used liquids for human comsumptions are
 Oil active ingredients e.g. clofibrate
 Vegetable oils e.g. soybean oil
 Mineral oil, non-ionic surfactants e.g. polysorbate 80 and PEG (400 and 600) either alone or in combination
 Fish oils in vitamin capsules.
Other conditions for manufacturing soft gelatin capsules

1. The suspension products must be homogeneous, air free and preferably should flow by gravity at room
temperature but not a temperature above 350C because the sealing temperature of gelatin films is usually 37
to 400C.
2. pH should be in between 2.5 and 7.5, since preparations that are more acidic can cause hydrolysis and
leakage of the gelatin shell, and preparations those are more alkaline can tan the gelatin and thus affect the
solubility of the shell.

CAPSULE MANUFACTURING
Plate process: It is the oldest process, contains sets of plates containing die packets.
Rotary die process
Reciprocating die process
Accogel machine is unique in that it is the only equipment that accurately fills powdered dry solids into soft
gelatin capsules.
PROCESS
Gelatin preparation department
(i) Weighing of gelatin Mixed in
Weighing of other liquids  chilled at 70C Pony mixer
(ii) The resultant fluffy mixture transferred to melting tanks and melted under vacuum at 930C
(iii) A sample of the resulting fluid mass is visually compared with a color standard, and additional
colorants are added if required.
(iv) The mass is then maintained at 57 to 600C before and during capsulation process.
Material preparation department
(i) Blending  milling or homogenization

Equipments: Homoloid mill
Stone mill
Hopper mill
Urschel comitrol
(ii) Deaeration all mixtures are subjected to deaeration by
To achieve uniform capsule fill weight
And it reduces oxidation of the product.
Most liquids and suspensions may be deaerated by means of equipment designed to expose thin layers of the
material continuously to a vacuum (29.5 mm Hg).
(iii) After deaeration the volatile ingredients are added and blended.

Material filling by rotary die process
 The gelatin mass is fed by gravity to a metering
device (spreader box), which control the flow of the
mass onto air cooled (13 to 140C) rotating drums.
Gelatin ribbons of controlled thickness are formed.
The wet film thickness may vary from 0.022 to
0.045 inch.
 The ribbons are fed through mineral oil lubricating
bath, over guide rolls, and then down between the
wedge and the die rolls.
 The materials to be encapsulated flows by gravity
into a positive displacement pump. The pump
accurately meters the material through the leads and
wedges and into the gelatin ribbons between the die
rolls. The bottom of the wedge contains small
orifices lined up with the die pockets of the die rolls.
 The capsule is about half sealed when the pressure
of the pumped material forces the gelatin into the die pockets, where the capsules are simultaneously filled,
shaped, hermetically sealed, and cut from the gelatin ribbon. The sealing of the capsule is achieved by
mechanical pressure on the die rolls and the heating (37 to 400C) of the ribbons by the wedge.
 Immediately after the manufacture, the capsules are automatically conveyed through a naphtha wash unit to
remove the mineral lubricating oil.
 The washed capsules may be automatically subjected to a preliminary infrared drying step which removes 60
to 70% of the water that is to be lost, or may be manually spread directly on trays. All the capsules are
allowed to come to equilibrium with forced air conditions of 20 to 30 % relative humidity at 21 to 240C.

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 PREFORMULATION
PREFORMULATION
Definition:
Preformulation may be described as a phase of the research and development process
where the preformulation scientist characterizes the physical, chemical and
mechanical properties of a new drug substance, in order to develop stable, safe and
effective dosage form.
Objectives:
The preformulation investigations confirm that there are no significant barriers to the
compound’s development as a marketed drug. The formulation scientist uses these
informations to develop dosage forms.
Preformulation is a multidisciplinary development of a drug candidate. See TABLE-1
Principal areas of preformulation

1. Bulk characterization
(i) Crystallinity and polymorphism
(ii) Hygroscopicity
(iii) Fine particle characterization
(iv) Powder flow
2. Solubility analysis
(i) Ionization constant – pKa
(ii) pH solubility profile
(iii) Common ion effect – KSP.
(iv) Thermal effects
(v) Solubilization
(vi) Partition coefficient
(vii) Dissolution
3. Stability Analysis
(i) Stability in toxicology formulation
(ii) Solution stability
– pH stability profile
(iii) Solid state stability
– Bulk stability
– Compatibility

1. Bulk characterization
When a drug molecule is discovered all the solid-forms are hardly identified. So during
bulk characterization the following characteristics are studied.
(i) Crystallinity and polymorphism
Chemical Compounds
Habit Internal Structure
Crystalline
Amorphous
Single Entity Molecular Adduct

POLYMORPHS
Non-stoichiometric Stoichiometric
Inclusion compounds solvates / hydrates
Channel Layer Cage

(Clathrate)

TABLE –1
Medicinal Chemistry Preformulation Formulation Process Research Analytical Research Toxicology and
And Pharmacology Research Development And Development And Development Drug Metabolism
Drug Discovery
Literature Search
Preliminary Data
– stability assay
Molecular Optimization – key stability data
– salts and solvates – key solubility data
– prodrugs
Evaluation and Selection of Drug

Time Increasing
Formulation Request
Physical Characterization Process Research Analytical Research

– bulk properties – improve yield – assay development
– solubility profile
– stability profile
– alternate route
– produce bulk
Analytical Bioavailability
Formulation Development Development – in vivo models
Process Development
– compatibility and stability – bulk clearance
– dissolution – bulk scale-up
– toxicology
– bioavailability potency Toxicology
– acute
– formulation assay – chronic
Phase-I Formulation – IND formulation
– IND stability stability
– Bioavailability
– Scale-up
Investigational New Drug (ND) Application

 Flowability of powder and chemical stability depends on the habit and internal
structure of a drug.
Habit is the description of the outer

Needle or Acicular
appearance of a crystal. A single
Platy
Tabular
internal-structure for a compound can
have several different habits, depending
Bladed
on the environment for growing crystals. Equant or Massive
Different habits of crystals are given Fig. 1 Prismatic
below.
Internal Structure
Crystalline state
In this state of matter atoms or molecules are arranged in highly ordered form and is
associated with three-dimensional periodicity.
[N.B. Atoms or molecules tend to organize themselves into their most favorable
thermodynamic state, which under certain conditions results in their appearance as crystals.
N.B. The repeating three-dimensional patterns are called crystal lattices. The crystal lattice
can be analyzed from its X-ray diffraction pattern.]
Amorphous forms
In this forms the solids do not have any fixed internal structure. They have atoms or
molecules randomly placed as in a liquid.
e.g. Amorphous Novobiocin
[N.B. Amorphous forms are prepared by rapid precipitation, lyophillization or rapid cooling
of molten liquids e.g. glass]

DIFFERENCE BETWEEN CRYSTALLINE AND AMORPHOUS FORM
Crystalline forms Amorphous forms
(i) Crystalline forms have fixed internal (i) Amorphous forms do not have any fixed
structure internal structure
(ii) Crystalline forms are more stable than its (ii) Amorphous form has higher
amorphous forms. thermodynamic energy than its crystalline
(iii)Crystalline forms are more stable than its form.
amorphous forms. (iii) Amorphous forms are less stable than its
(iv) Crystalline form has lesser solubility than crystalline forms.
its amorphous form. (iv) Amorphous forms have greater solubility
(v) Crystalline form has lesser tendency to than its crystalline forms.
change its form during storage. (v) Amorphous tend to revert to more stable
forms during storage.
Polymorphs
When a substance exists in more than one crystalline form, the various forms are
called Polymorphs and the phenomenon as polymorphism.
E.g. Chloramphenicol palmitate has three polymorphs A, B and C.
[N.B. various polymorphs can be prepared by crystallizing the drug from different drugs
under diverse conditions. Depending on their relative stability, one of the several
polymorphic forms will be physically more stable than the others. Such a stable polymorph
represents the lowest energy state, has highest melting point and least solubility. The
representing polymorphs are called metastable forms which represents higher energy state,
the metastable forms have a thermodynamic tendency to convert to the stable form. A
metastable form cannot be called unstable because if it is kept dry, it will remain stable for
years.]

Molecular Adducts
During the process of crystallization, some compounds have a tendency to trap the
solvent molecules.
1. Non-Stoichiometric inclusion compounds (or adducts)
In these crystals solvent molecules are entrapped within the crystal lattice and the number
of solvent molecules are not included in stoichiometric number. Depending on the shape they
are of three types:-
(1) Channel
When the crystal contains continuous channels in which the solvent molecule can be
included. E.g. Urea forms channel.
(2) Layers: - Here solvent molecules are entrapped in between layers of crystals.
(3) Clathrates (Cage):- Solvent molecules are entrapped within the cavity of the crystal from
all sides.
2. Stoichiometric inclusion compounds (or stoichiometric adducts)

This molecular complex has incorporated the crystallizing solvent molecules into specific
sites within the crystal lattice and has stoichiometric number of solvent molecules complexed.
When the incorporated solvent is water, the complex is called hydrates and when the
solvent is other than water, the complex is called solvates. Depending on the ratio of water
molecules within a complex the following nomenclature is followed.
(i) Anhydrous : 1 mole compound + 0 mole water
(ii) Hemihydrate: 1 mole compound + ½ mole water
(iii) Monohydrate: 1 mole compound + 1 mole water
(iv) Dihydrate : 1 mole compound + 2 moles water
Properties of solvates / hydrates

(i) Generally, the anhydrous form of a drug has greater aqueous solubility than its hydrates.
This is because the hydrates are already in equilibrium with water and therefore have less
demand for water. E.g. anhydrous forms of Theophyline and ampicillin have higher
aqueous solubility than the hydrates.
(ii) Non aqueous solvates have greater aqueous solubility than the non-solvates. E.g.
chloroform solvates of Griseofulvin are more water soluble than their nonsolvate forms.

ANALYTICAL METHODS FOR CHARACTERIZATION OF SOLID FORMS
Methods of studying solid forms are listed as below:
Method Material required per sample
Microscopy 1 mg
Hot stage microscopy 1 mg
Differential Scanning Calorimetry (DSC) 2 – 5 mg
Differential Thermal Analysis (DTA) 2 – 5 mg
Thermogravimetric Analysis 10 mg
Infrared Spectroscopy 2 – 20 mg
X-ray Powder Diffraction 500 mg
Scanning Electron Microscopy 2 mg
Dissolution / Solubility Analysis mg to gm
Microscopy
In this type of microscope light passes through cross-polarizing filters.
Amorphous substances (e.g. super-cooled glass and non-crystalline organic compounds or
substances with cubic crystal lattices e.g. NaCl) have single refractive index. Through this
type of microscope the amorphous substances do not transmit light, and they appear black.
They are called isotropic substances.
Hot-stage microscopy
In this case, the polarizing microscope is fitted with a hot stage to investigate
polymorphism, melting points, transition temperatures and rates of transition at controlled rates.
It facilitates in explaining the thermal behavior of a substance from the DSC and TGA
curves.
[N.B. A problem often encountered during thermal microscopy is that organic molecules can
degrade during the melting process, and recrystallization of the melt may not occur, because
of the presence of contaminant degradation products. ]

Thermal Analysis
Differential Thermal Analysis

In DTA instrument a record Exothermic peak
is produced where temperature
T
difference (T) (between the
sample and reference material) is Endothermic peak
plotted against temperature (T) Fig 2.
T
when two specimens are subjected
to an identically controlled temperature regime.
The reference material is alumina, keiselguhr.
Differential Scanning Calorimetry

In DSC method the difference in energy inputs (H) into a sample and reference
material is measured as a function of
Polymorphism of Phemobarbitone studied by DSC
temperature as the specimens are subjected
to a identically controlled temperature
programme. Fig. 3
H
Samples that may be studied by DSC or 150 160 170 180 190
T
DTA are:
Powders, fibres, single crystals, polymer films, semi-solids or liquids.
Applications of DTA / DSC in preformulation studies

1. To determine the purity of a sample
2. To determine the number of polymorphs and to determine the ratio of each
polymorph.
3. To determine the heat of solvation
4. To determine the thermal degradation of a drug or excipients.
5. To determine the glass-transition temperature (tg) of a polymer.

Thermogravimetric Analysis (TGA)

TGA measures the changes in sample weight as a function of time (isothermal changes) or
temperature.
% Weight
Application of TGA in preformulation study Remaining
1. Desolvation and decomposition Fig. 4
processes are monitored. 40 Temperature 170
2. Comparing TGA and DSC data

recorded under identical conditions can
greatly help in the explanation of the thermal process.
TGA and DSC analysis of an acetate salt

of an organic amine that has two
crystalline forms, anhydrous and
dihydrate are shown above. Anhydrous /
dihydrate (10:1) mixture was prepared by
dry blending. Heating rate was 50C/min.
From DSC curve, it is evident
that the dihydrate form loses two
molecules of water via an endothermic
transition between 700C and 900C. The
second endotherm at 1550C corresponds
to melting process.
From TA curve, it is evident that
at 70 – 900C weight-loss was due to the
loss two molecules of water and the
weight loss at 1550C was due to vaporization of acetic acid and decomposition.
X-RAY POWDER DIFFRACTION

When a X-ray beam falls on a powder the beam is diffracted. This diffraction in found only in
case of crystalline powder. Amorphous forms do not show X-ray diffraction.

Uses:
(i) Each diffraction pattern is characteristic of a
6 Fig. 6
specific crystalline lattice for a given compound.
5
So in a mixture different crystalline forms can be 4
Intensity 3
analyzed using normalized intensities at specific
2
angles.
1
(ii) Identification of crystalline materials by using their
20 40 60 80 100
diffraction pattern as a ‘finger print’. First, the % From B
powder diffraction photograph or diffractometer trace are taken and matched with a
standard photograph. All the lines and peaks must match in position and relative intensity.
HYGROSCOPICITY
Definition: Many pharmaceutical materials have a tendency to adsorb atmospheric moisture
(especially water-soluble salt forms). They are called hygroscopic materials and
this phenomenon is known as hygroscopicity.
Equilibrium moisture content depends upon:
(i) The atmospheric humidity
(ii) Temperature
(iii) Surface area
(iv) Exposure time
(v) Mechanism of moisture uptake.
Deliquescent materials:
They absorb sufficient amount of moisture and dissolve completely in it.
(e.g. anhydrous calcium chloride).
Tests of hygroscopicity
powder sample
desiccator
Procedure shallow
container
Bulk drug samples are placed in open
saturated salt
containers with thin powder bed to assure solution
maximum atmospheric exposure. These Fig. 7
samples are then exposed to a range of controlled relative humidity (RH) environments
prepared with saturated aqueous salt solutions.

The amount of moisture adsorbed can be determined by the following methods:

(i) Gravimetry
(ii) Thermogravimetric analysis (TGA)
(iii) Karl-Fischer titration (KF-titration)
(iv) Gas chromatography (GC)
Time of monitoring depends on the purpose:
(i) For the purpose of ‘handling’ data points from 0 to 24 hours are taken
(ii) For the purpose of ‘storage’ data points from 0 to 12 weeks are taken.
Significance of hygroscopicity test
(a)
To decide special handling procedure

mg H 2O % weight
g sample gain (with respect to time).
time time
Fig. 8
(b)
Equilibrium
moisture To decide
content Fig. 9
(i) the storage condition i.e. at low humidity environment.
mg H 2O
g sample
(ii) special packaging – e.g. with desiccant.
RH
(c) Moisture level in a powder sample may affect the flowability and compactibility which,
are important factors during tableting and capsule filling.
(d) After adsorption of moisture, if hydrates are formed then solubility of that powder may
change affecting the dissolution characteristics of the material.
(e) Moisture may degrade some materials. So humidity of a material must be controlled.

FINE PARTICLE CHARACTERIZATION

Parameters those are measured:
(i) particle size and size-distribution
(ii) shape of the particle
(iii)surface morphology of the particles
Instrumental methods of particle size characterization
(i) Light microscope

First a standard graticule (BS 3625) is standardized with a stage micrometer. Then
small number of particles are spread over a glass slide and placed on the stage of the
microscope. Particles are focussed and the particle diameters are measured. Several hundred
particles are measured and reported as a histogram.
Disadvantage: The procedure is time consuming.
(ii) Stream counting devices

Examples: (a) Coulter counter – electrical sensing zone method
(b) HIAC – counter – optical sensing zone
(c) Malvern particle & droplet sizer – Laser diffraction method.
Procedure: To vacuum
Samples prepared for analysis are dispersed in a
conducting medium (e.g. saline) with the help of
ultrasound and a few drops of surfactant (to disperse the
To amplifier
particles uniformly). A known volume (0.5 to 2 ml) of and counter
this suspension is then drawn into a tube through a small

aperture (0.4 to 800 m diameter) across which a voltage Stirrer
is applied.
As each particle passes through the hole, it is counted and . . .. Electrodes
sized according to the resistance generated by displacing . .. . .
. . . Orifice
that particle’s volume of conducting medium. .
. . .. .
Size distribution is reported as histogram.
Fig. 10 Coulter counter

(iii) Sieve analysis

A powder sample is passed through a standard sieve set. The particle size is plotted against
% weight retained on each sieve.
Use: This method is used generally for large samples.
Instrumental method for determination of specific surface area

Brunauer, Emmett and Teller (BET) nitrogen adsorption method:
A layer of nitrogen molecules is adsorbed to the sample surface at –1960C. Once the
surface is saturated, the sample is heated to room temperature, the nitrogen gas is desorbed,
and its volume is measured and converted to the number of adsorbed molecules via the gas
law. Since each N2 molecule occupies an ara of 16 A2, one may readily compute the surface
area per gram of each pre-weighed sample.
Instrumental method for characterization of surface morphology
The scanning electron microscope creates the magnified images by using electrons instead of
light waves. The images are black and white.
Procedure
 Biological materials are dried in a special way that prevents them from shrinking.
 Since SEM illuminates them with electrons, they are made conductive by coating with a
very thin layer of gold by a machine called sputter-coater.
 The sample is placed inside the microscope’s vacuum column through an airtight door.
 After the air is pumped out of the Electron gun
column, an electron gun emits a beam Vacuum column
of high-energy electrons. This beam Condensing
Monitor
lenses
travels downward through a series of
magnetic lenses designed to focus the
Scan coils
electrons to a very fine spot.
 Near the bottom, a set of scanning Objective lens
coils moves the focussed beam back Secondary
Electron
and forth across the specimen, row by Electron
beam
row.
Target Detector &
 As the electron beam hits each spot on Amplifier
the sample, secondary electrons are
Fig. 11 Scanning Electron Microscope
knocked loose from its surface.

 A detector counts these electrons and sends the signals to an amplifier.

 The final image is built up from the number of electrons emitted from each spot on the
sample.
BULK DENSITY
Apparent Bulk Density (g/cm3)
Bulk drug powder is sieved through 40 mesh screen. Weight is taken and poured into a
graduated cylinder via a large funnel. The volume is called bulk volume.
Weight of the powder
Apparent Bulk Density 
Bulk Volume
Tapped density (g/cm3)
Bulk powder is sieved through 40 mesh screen. Weight is taken and poured into a graduated
cylinder. The cylinder is tapped 1000 times on a mechanical tapper apparatus. The volume
reached a minimum – called tapped volume.
Weight of the powder
Tapped density 
Tapped volume
True density (g/cm3)
Solvents of varying densities are selected in which the powder sample is insoluble. Small
quantity of surfactant may be mixed with the solvent mixture to enhance wetting and pore
penetration. After vigorous agitation, the samples are centrifuged briefly and then left to
stand undisturbed until floatation or settling has reached equilibrium.
The samples that remains suspended (i.e. neither suspended not floated) is taken. So the true
density of the powder are equal. So the true density of the powder is the density of that
solvent. The density of that solvent is determined accurately with a pycnometer.
Source of variation of bulk density
Method of crystallization, milling, formulation.
Methods of correction
By milling, slugging or formulation.
Significance
(i) Bulk density
Bulk density is required during the selection of capsule size for a high dose drug.
In case of low dose drug mixing with excipients is a problem if the bulk densities of
the drug and excipients have large difference.

(ii) Tapped density

Fig. 12
Knowing the dose and tapped 000 1.4
density of the formulation, the 00 1.2
0 1.0
capsule size can be determined.
Capsule 8
Capsule
1
size volume
2 6 (ml)
(iii) True density 3 4
4
From bulk density and true 5 2
density of powder, the void 0.4 0.5 0.6 0.7 0.8 0.9
Packed density (g/ml)
volume or porosity can be
measured.
 m m   1 1 
Void volume      m   
  bulk  ture    bulk  true 
 1 1 
m   
Void volume   true   1   bulk
Porosity    bulk
Bulk volume m  true
 bulk
Powder flow properties

Powder flow properties depends on
(i) particle size
(ii) density
(iii)shape
(iv) electrostatic charge and adsorbed moisture
That may arise from processing or formulation.

A free-flowing powder may become cohesive during development. This problem may be
solved by any of the following ways.
(i) by granulation
(ii) by densification via slugging
(iii)by filling special auger feed equipment (in case of powder)
(iv) by changing the formulation.

Procedure Fig. 13
For free flowing powder
g/sec
A simple flow rate apparatus consisting of a
grounded metal tube from which drug flows through an time
orifice onto an electronic balance, which is connected to a Nozzle Plotter

Powder
strip chart recorder. Several flow rate (g/sec) determinations
at various orifice sizes (1/8 to ½ inch) should be carried out.
The grater the standard deviation between multiple
flow rate measurements, the greater will be the weight Digital Balance
variation of the product (tablets or capsules).
Compressibility :-
t  0
% compressib ility  x 100
t
t = tapped bulk density
0 = Initial bulk density
Solubility Analysis
Determination of equilibrium solubility of a drug

Equilibrium
solubility conc.
The drug is dispersed in a solvent. The
Plateau Fig. 14
suspension is agitated at a constant temperature. Conc.
Samples of the suspension are withdrawn as a
function of time, clarified by centrifugation, and Time
assayed to establish a plateau concentration.
Solvents taken
(i) 0.9% NaCl at room temperature
(ii) 0.01 M HCl at RT
(iii) 0.1 M HCl at RT
(iv) 0.1 M NaOH at RT
(v) At pH 7.4 buffer at 370C

Drug concentration is determined by the following analytical methods

(i) HPLC
(ii) UV –Spectroscopy
(iii)Fluorescence Spectroscopy
(iv) Gas Chromatography
Solubility depends on
(i) pH
(ii) Temperature
(iii)Ionic strength
(iv) Buffer concentration
Significance
(i) A drug for oral administrative should be examined for solubility in an isotonic saline
solution and acidic pH. This solubility data may provide the dissolution profile invivo.
(ii) Solubility in various mediums is useful in developing suspension or solution
toxicologic and pharmacologic studies.
(iii) Solubility studies identify those drugs with a potential for bioavailability problems.
E.g. Drug having limited solubility (7 %) in the fluids of GIT often exhibit poor or
erratic absorption unless dosage forms are tailored for the drug.
pKa Determination
When a weakly acidic or basic drug partially ionizes in GI fluid, generally, the unionized
molecules are absorbed quickly.
Handerson-Hasselbalch equation provides an estimate of the ionized and unionized drug
concentration at a particular - pH.
HA + H 2O H3O+ + A
For acidic Drug:
Weak Strong
e.g. acid base
[ionized ] [ A ] [base]
pH  pKa  log  pKa  log  pKa  log
[unionized ] [ HA] [acid ]

For basic compounds e.g.

B + H 3O+ BH + + H2O
Weak Strong
base acid
[unionized] [ B] [base]
pH  pKb  log  pKa  log  pKa  log
[ionized] [ BH  ] [acid]
Drug Stomach Plasma Duodenum

PH 1.5 PH = 7.4 PH = 5.0
[HA] = 100 [HA] = 100 [HA] = 100

Weak acid
e.g. Ibuprofen
[A --] = 0.13 [A--] = 100,000 [A--] = 398.1
pKa = 4.4
[Total] = 100.13 [Total] = 100,100 [Total] = 498.1
[B] = 100 [B] = 100 [B] = 100
[BH +] = 5012 [BH +] = 0.006 [BH +] = 1.6
[Total] = 5112 [Total] = 100.006 [Total] = 101.6

Weak base
e.g. Nitrazepam
pKa = 3.2
Method of determination of pKa of a drug
(i) Detection of spectral shifts by UV or visible spectroscopy at various pH.

Advantage: Dilute aqueous solutions can be analyzed by this method.
(ii) Potentiometric titration
Advantage: Maximum sensitivity for compounds with pKa in the range of 3 to 10.

Disadvantage: This method is unsuccessful for candidates where precipitation

of the unionized forms occurs during titration. To prevent precipitation
a co-solvent e.g. methanol or dimethylsulfoxide (DMSO) can be
incorporated.
(iii) Variation of solubility at various pH.
Effect of temperature on stability

Heat of solution, HS represents the heat released or absorbed when a mole of solute is
dissolved in a large quantity of solvent.
Significance
 Most commonly, the solubility process is endothermic, e.g. non-electrolytes, unionized
forms of weak acids and bases  H is positive  Solubility increases if temperature
increases.
 Solutes that are ionized when dissolved releases heat
 the process is exothermic  HS is negative  Solubility increases at lower
temperature.
Determination of HS.
H S  1 
The working equation ln S      C where, S = molar solubility of the
R T 
drug at T0K
and R = gas constant
S is detemined at 50C, 250C, 370C and 500C.
HS = – Slope x R s
Slope =
R
lnS
Solubilization 1
For drug candidates with poor water solubility, T

preformulation studies should include limited experiments to identify the possible
mechanisms for solubilization.

Means of increasing the solubility are:

(i) Addition of a cosolvent to the aqueous system e.g. ethanol, propylene glycol and glycerin.
MOA: These co-solvents disrupt the hydrophobic interactions of water at the non-
polar solute / water interfaces.
(ii) Solubilization in micellar solutions such as 0.01 M Tween 20 solution.
(iii) Solubilization by forming molecular complexes e.g. benzoic acid forms complex with caffeine.
Partition coefficient
Partition coefficient is defined, as the ratio of un-ionized drug concentrations between the
organic and aqueous phases, at equilibrium.
 C 
K O / W   oil  at equilibrium
 C water 
Generally, Octanol and chloroform are taken as the oil phase. IMP
Significance: Drug molecules having higher KO/W will cross the lipid cell membrane.
Dissolution
The dissolution rate of a drug substance in which surface area is constant during
disintegration is described by the modified Noyes-Whitney equation.
dc DA
 ( CS  C )
dt hV
Where, D = diffusion coefficient of the drug in the dissolution medium
h = thickness of the diffusion layer at the solid/liquid interface
A = surface area of drug exposed to dissolution medium.
V = volume of the medium
CS = Concentration of saturated solution of the solute in the dissolution medium at the
experimental temperature.
C = Concentration of drug in solution at time t.
When A = constant and CS >> C the equation can be rearranged to
dC DA V dC DA D
 CS or ,  CS or , W  k A t Where, k 
dt hV dt h h
where, W = weight (mg) of drug dissolved at time t
 mg  Slope = kA
k = intrinsic dissolution rate constant  2  W
 min cm 
time (t)

Determination of k
 Pure drug powder is punched in a die and punch apparatus to give a uniform cylindrical
shape. The tablet is covered with wax in all sides. One circular face is exposed to the
dissolution medium. Thus, as dissolution proceeds, the area, A, remains constant.
 Time to time dissolution medium is taken out and fresh
medium added to the chamber.
 With two types of assembly, the experiments can be
carried out.
. ... ...
Stability analysis .. ... ....
Preformulation stability studies are the first quantitative Static disc Rotating disc
assessment of chemical stability of a new drug. This may dissolution dissolution
aparatus apparatus
involve
1. Stability study in toxicology formulation
2. Stability study in solution state
3. Stability study in solid state.
Stability study in toxicology formulation

A new drug is administered to animals through oral route either by
(i) mixing the drug in the feed
(ii) in the form of solution
(iii)in the form of suspension in aqueous vehicle
 Feed may contain water, vitamin, minerals (metal ions), enzymes and different functional
groups that may severely reduce the stability of the new drug. So stability study is should
be carried out in the feed and at laboratory temperature.
 For solution and suspension, the chemical stability at different temperature and pH should
be checked.
 For suspension-state the drug suspension is occasionally shaken to check dispersibility.
Solution stability
Objective: Identification of conditions necessary to form a stable solution.
Stability of a new drug may depend on:
(i) pH (ii) ionic strength (iii) co-solvent
(iv) light (v) temperature (vi) oxygen.

pH stability study
(i) Experiiments to confirm decay at the extremes of pH and temperature. Three stability
studies are carried out at the following conditions
(a) 0.1N HCl solution at 900C
(b) Solution in water at 900C
(c) 0.1 N NaOH solution at 900C
These experiments are intentionally done to confirm the assay specificity and for maximum
rates of degradation.
(ii) Now aqueous buffers are used to produce solutions with wide range of pH values but with
constant levels of drug concentration, co-solvent and ionic strength.
All the rate constants (k) at a single temperature are then plotted as a function of pH.
(ii) Ionic strength

Since most pharmaceutical solutions are intended for parenteral routes of administration,
the pH-stability studies should be carried out at a constant ionic strength that is
compatible with body fluids. The ionic strength () of an isotonic 0.9%w/v sodium
chloride solution is 0.15.
Ionic strength for any buffer solution can be calculated by
1 2

2
 mi Z i
where, mi = molar concentration of the ion

Zi = valency of that ion
For computing,  all the ionic species of the buffer solution and drugs are also taken into
calculation.

(iii) Co-solvents
Some drugs are not sufficiently soluble to give concentrations of analytical sensitivity. In
those cases co-solvents may be used. However, presence of co-solvents will influence the rate
constant. Hence, k values at different co-solvent concentrations are determined and plotted
against % of co-solvent. Finally, the line is extrapolated to 0% co-solvent to produce the
actual k value (i.e. in pure solvent).
(iv) Light
Drug solutions are kept in
(a) clear glass ampoules
(b) amber color glass container
(c) yellow-green color glass container
(d) container stored in card-board package or wrapped in aluminium foil – this one
acts as the control.
Now the stability studies are carried out in the above containers.
(v) Temperature
The rate constant (k) of degradation reaction of a drug varies with temperature according to
Arrhenius equation.
Ea
 Ea  1 
RT
k  Ae or , ln  ln A   
R T 
where, k = rate constant Ea
Slope =
A = frequency factor ln k R
Ea = energy of activation
R = gas constant 1/ T
T = absolute temperature
Procedure
Buffer solutions were prepared and kept at different temperatures. Rate constants are
determined at each temperature and the ln k value is plotted against (1/T)).
Inference
 The relationship is linear  a constant decay mechanism over the temperature range
has occurred.

 A broken or non-linear relationship  a change in the rate-limiting step of the

reaction or change in decay mechanism.
Uses
Shelf life of the drug may be calculated.
e.g. Time Concentration of drug remaining
0 100 %
t10% 90%
Therefore, ln C = ln C0 – k1t
Ln C/C0 = – k1t
90 ln 0.90 0.105
or, ln   k1t10% or, t10%  
100  k1 k1
where, t10% = time for 10% decay to occur if the reaction follows 1st order kinetics
Conclusion
If the drug is sufficiently stable, liquid formulation development may be started at once.
If the drug is unstable, further investigations may be necessary.
Solid state stability

Objectives
Identification of stable storage conditions for drug in the solid state and identification of
compatible excipients for a formulation.
Characteristics
Solid state reactions are much slower, so the rate of appearance of decay product is measured
(not the amount of drug remaining unchanged).
 To determine the mechanism of degradation thin layer chromatography (TLC),
fluorescence or UV / Visible spectroscopy may be required.
 To study polymorphic changes DSC or IR-spectroscopy is required.
 In case of surface discoloration due to oxidation or reaction with excipients, surface
reflectance equipment may be used.

A sample scheme for determining the bulk stability profile of a new drug:
Storage condition 4 weeks 8 weeks 12 weeks

50C – Refrigerator
220C – Room Temperature
370C – Ambient humidity
370C / 75% RH (Relative Humidity)
Light box
Clear box
Amber glass
Yellow-Green glass
No exposure (Control:- Card-board box or wrapped with aluminium foil)
500C – Ambient Humidity
– O2 Head Space
– N2 Head Space
Procedure
1. Weighed samples are placed in open screw-capped vials are exposed to a variety of
temperatures, humidities and light intnesities. After the desired time samples are taken out
and measured by HPLC (5 – 10 mg), DSC (10 to 50mg), IR (2 to 20mg).
2. To test for surface oxidation samples are stored in large (25ml) vials for injection capped
with Teflon-lined rubber stopper. The stoppers are penetrated with needles and the
headspace is flooded with the desired gas. The resulting needle holes are sealed with wax
to prevent degassing.
3. After fixed time those samples are removed and analyzed.
Drug-excipient stability profile

Hypothetical dosage forms are prepared with various excipients and are exposed to various
conditions to study the interactions of drug and excipients.

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 EMULSION
EMULSION
Syllabus:
Definitions, general formulation of an emulsion and the components used in the formulation of emulsions with
examples: Emulsifying agents, oil phase ingredients, aqueous phase ingredients, preservatives, stabilizers,
coloring and flavouring agents and such other components processing and equipments on industrial scale. An
account of lotions, creams, collodions with the processing and equipment.
Questions:
Q.1 What are emulsions and emulsifying agents? Give examples. [8]
Q.2. Give any one method of formulation of emulsion and production on large scale with different additives. (98)
[8]
Q.3. Explain the different mechanical equipments those are at present available for emulsification. (96) [8]
Q.4. Discuss problems that may arise in production of emulsions. (96) [8]
Q.5. Write notes on auxiliary emulsifiers.
DEFINITION
An emulsion is a thermodynamically unstable dispersed system consisting of at least two immiscible liquid
phase, one of which is dispersed as globules in the other liquid phase.
The system is stabilized by the presence of an emulsifying agent.
Emulsified systems range from lotions of relatively low viscosity to ointments and creams, which are
semisolid in nature.
The particle diameter of the dispersed phase generally extends from about 0.1 to 10 m and as 100 m are
not uncommon in some preparations.
TYPES OF EMULSIONS
(I) Ordinary emulsion systems / Primary emulsion systems / Simple emulsion systems
(i) o/w type  oil dispersed in water
oil  dispersed phase
water  continuous phase
(ii) w/o type  water dispersed in oil
water  dispersed phase
oil  continuous phase
(II) Special emulsion systems
(i) Multiple emulsions  w/o/w  type
o/w/o  type
(ii) Micro emulsion
Simple emulsion type:

o/w- type of emulsion is a system in which the oil is dispersed as droplet throughout the aqueous phase.
Most pharmaceutical emulsions designed for oral administration are of the o/w type; emulsified lotions and
creams either of o/w or w/o type depending on their use.
Certain foods such as butter and some salad creams are w/o type emulsions.
Multiple emulsion type
These multiple emulsions have been developed with a view to delay the release of an active ingredient. In
this type of emulsions three phases are present, i.e. the emulsion has the
form w/o/w or o/w/o. In these “emulsions within emulsions”, any drug
present in the innermost phase now has to cross two phase-boundaries to
reach the external continuous phase.
I : Continuous phase (External aqueous phase)
II: Middle oil phase
III: Inner aqueous phase

Advantages of multiple emulsions

(i) Prolongation of drug action
(ii) Location of drug in the body.
Micro emulsions
Microemulsions are liquid dispersion of water and oil that are made homogeneous, transparent and stable by the
addition of relatively large amount of a surfactant and a co-surfactant. They appear to represent a state
intermediate between thermodynamically unstable emulsions and solubilized systems.
Unlike emulsions, they appear as clear transparent solution, but unlike solubilized systems micro-
emulsions may not be thermodynamically stable.
Microemulsions containing droplets (w/o or o/w types) with the globule size 10 to 200nm and the volume
fraction of the dispersed phase varies from 0.2 to 0.8.
DETERMINATION OF EMULSION TYPE

Several methods are commonly used to determine the type of emulsion. The types of emulsion determined
by one method should always be confirmed by means of second method.
(1) Dye solubility test
A small amount of a water soluble dye (e.g. methylene blue or brilliant blue) may be dusted on the surface of the
emulsion.
If water is the external phase (i.e. o/w type) then the dye will be dissolved uniformly throughout the
media.
If the emulsion is of the w/o -type then particles of dye will lie in clumps on the surface.
(2) Dilution test
This method involves dilution of the emulsion with water. If the emulsion mixes freely with the water, it
is of o/w -type. Generally, addition of disperse phase will crack an emulsion.
(3) Conductivity test
This test employs a pair of electrodes connected to an external electric source and immersed in the
emulsion. If the external phase is water, a current will pass through the emulsion and can be made to deflect a
volt-meter needle or cause a light in the circuit to glow. if the oil is the continuous phase then the emulsion will
fail to carry the current.
Methods for determination of emulsion type:
Test Observation Comments
1. Dilution test Emulsion can be diluted only with Useful for liquid emulsions only.
external phase.
2. Dye test Water-soluble solid dye tints only o/w May fail if ionic emulsifiers are
emulsion and reverse. Microscopic present.
observation usually is helpful.
3. Conductivity test Electric current is conducted by o/w Fails in nonionic o/w emulsions.
emulsions, owing to the presence of
ionic species in water.
4. Fluorescence test Since oils fluoresce under UV-light, Not always applicable
o/w emulsions exhibit dot pattern, w/o
emulsions fluoresce throughout.
5. CoCl2 / filter paper test Filter paper impregnated with CoCl2 May fail if emulsion is unstable or
and dried (blue) changes to pink when breaks in presence of electrolyte.
(o/w) emulsion is added.
FORMULATION OF EMULSION
In developing the formula of an emulsion the crucial decisions are related to the choice of the aqueous
and oil phases and of the emulgents and their relative proportions. There can be no general guideline in this
respect and the choice of phases and emulgents should be related to the qualities desired for the final product.
Usually, ingredient selection is made on the basis of the experience and personal tastes of the formulator and by
trial and error.

CHEMICAL PARAMETERS
Chemical stability
All the ingredients of an emulsion should be chemically compatible.
e.g. a soap cannot be used as an emulsifier in a system having a final pH of less than 5.
e.g. some lipids are subjected to chemical changes due to oxidation (rancidity); so in general it is simpler
to avoid their use than to depend on antioxidants
Safety
All the ingredients should pass the toxicological tests. It is essential, therefore, for the formulator to
depend heavily on toxicologic information from suppliers or in the scientific literature, and on regulatory
activities by governmental agencies.
Choice of lipid phase
The choice of lipid phase depends on the ultimate use of the product.
(i) If the oily phase is the active-ingredient itself (e.g. liquid paraffin emulsion) the formulator has nothing to
choose from.
(ii) The drug in a pharmaceutical preparation should not be too soluble in lipid phase then it will reduce the rate
of transfer of the drug molecule to other phases.
(iii) Emulsions prepared for topical purpose (e.g. cosmetics and pharmaceutical emulsions) should possess a good
“feel”. Emulsions normally leave a residue of the oily components on the skin after the water has evaporated.
Therefore, the tactile characteristics of the combined oil phase are of great importance in determining
consumer acceptance of an emulsion
Phase - volume ratio
The ratio of the internal phase to the external phase is frequently determined by the solubility of the
active ingredients, which must provide the required dose.
If this is not the primary criteria, the phase ratio is normally determined by the desired consistency of the
product. For liquid emulsions the limits of internal phase vary from 40 to 60%, since with such amounts a stable
and acceptable emulsion can be prepared. Lower amounts of internal phase (i.e. disperse phase) gives a product
of low viscosity with pronounced degree of creaming while higher percentage may produce highly viscous
emulsions with tendency of phase inversion.
TABLE 1: Ingredients for oil-phase of emulsions

Class Identity Consistency
Hydrocarbon Mineral oils Fluids of varying viscosity
Hydrocarbon Petrolatum Semisolid
Hydrocarbon Polyethylene waxes Solids
Hydrocarbon Microcrystalline waxes Solids
Ester Vegetable oils Fluids of varying viscosity
Ester Animal fats Fluids or solids
Ester Lanolin Semisolid
Ester Synthetic (e.g. isopropyl myristate) Fluids
Alcohols Long chain (natural & synthetic) Fluids or solids
Fatty acids Long chain (natural & synthetic) Fluids or solids
Ethers Polyoxypropylene Fluids of varying viscosity
Silicones Substituted silicones Fluids of varying viscosity
Mixed Plant waxes (e.g. Candellia) Solid
Mixed Animal waxes (e.g. Beeswax) Solid
Choice of emulsifying agents / Emulsifiers / Emulgents
Emulsifying agents are broadly classified into three classes:
(i) Synthetic emulsifying agent / Surface active agents (SAA) / Surfactants
(ii) Hydrophilic colloid
(iii) Finely divided solids
When an emulsifier is used alone to stabilize an emulsion  it is called primary emulsifier. Some times a second
emulsifier is used to help the primary emulsifier in stabilizing the system  the second emulsifier is known as
auxiliary emulsifier. Generally emulsifiers from (ii) and (iii) category are used both as primary and auxiliary
emulsifier.

A successful emulsifier must possess some or all of the following characteristics:

(a) The surface tension should be reduced to a value less than 10 dynes/cm2.
(b) A complete and coherent film should be formed around the dispersed globules so as to prevent their
coalescence.
(c) Should assist in building up the zeta potential and viscosity since both of these phenomena contribute to the
stability.
Choice of synthetic surface active agents / Surfactants:
Molecules and ions that are absorbed at interfaces are termed surface-active-agents
or surfactants. An alternative expression is amphiphile, which suggests that the molecule or
ion has a certain affinity for both polar and nonpolar solvents. Due to the amphiphilic nature
of surfactants they absorb at the oil-water interface.
Griffin devised an arbitrary scale of values to serve as a measure of the hydrophilic-
lipophilic balance (HLB) of surface-active -agents.
w/o emulsifiers o/w emulsifiers
0 3 6 9 12 15 18
Griffin’s HLB Scale

Mode of action of synthetic surfactants
This group of emulsifiers form a flexible film on the oil-water interface. They lower interfacial tension
markedly and this contribute to the stability of emulsion. In case of ionic surfactants surface charge is developed,
increasing the zeta-potential, which will cause repulsion between two adjacent globules.
e.g. Sodium lauryl sulphate
Polyoxyethylene sorbitan mono oleate (Polysorbate 80).
Classification of synthetic Surface Active Agents
Chemical formula (in aqs. soln.)
Lipophilic Surface
Class Surface Active Agent group Hydrophilic group inactive
ion
1. Anionic
(a) Alkali soap Potassium stearate C17H35 COO K+
(b) Organic Sodium lauryl sulphate C12H25 OSO3 Na+
sulphates (Sod. dodecyl sulphate)
(c) Organic Sodium cetyl sulphonate C16H33 SO3 Na+
sulphonates (Sod. hexadecane
sulfonate)
2. Cationic
(a) Quaternary Cetyl trimethyl C16H33 N+(CH3) 3 Br
ammonium ammonium bromide (or
compounds cetrimide)
(b) Pyridinium Dodecyl pyridinium C12H25 N+C5H5 Cl
compounds chloride
3. Ampholytic In alkaline soln. anionic

Amino acids N-dodecyl alanine C12H25 NH  CH2 CH2 COO Na+
In acid solution  cationic
C12H25 N+H2  CH2 CH2 COOH Cl
At isoelectric point  zwitterion
C12H25 N+H2  CH2 CH2 COO none
Chemical formula (in aqs. soln.)

Lipophilic Surface
Class Surface Active Agent group Hydrophilic group inactive ion
4. Non-ionic
(a) Alcohol- Polyethylene glycol 1000 CH2(CH2)n (OCH2CH2)mCOO none
polyethylene monocetyl ether (n= 15 to 17) (m = 20 to 24)
glycol ethers (cetomacrogol 1000)
(b) Fatty acid- Polyethylene glycol 40 C17H33 CO(OCH2CH2)40OH none
polyethylene monostearate
glycol ethers
(c) Fatty acid- Sorbitan mono-oleate C17H33 O none
COO CH2
polyhydric (TWEEN)
HO OH
alcohol esters OH
O
Polyoxyethylene sorbitan C17H33 COO CH2 none
mono-oleate H(O CH2 CH2)nO O(CH2 CH2 O)nH
O(CH2 CH2 O)nH
The HLB number of surfactants may vary from 40 (sodium lauryl sulfate) to 1 (oleic acid). Emulsifying
agents, sometimes used singly, are preferably a combination of two emulsifying agents, which will give a
weighted HLB of 8 to 16 which is satisfactory for o/w emulsions and an HLB 3 to 8 for w/o emulsions.
NOTE: The HLB required for emulsifying a particular oil in water can be determined by trial and error method;
i.e. by preparing appropriate emulsions with emulsifiers having a range of HLB values and then determining that
HLB values that yields the “best emulsion”. That HLB value is named as Required HLB or RHLB”.
TABLE : REQUIRED HLB VALUE FOR SOME OIL PHASE INGREDIENTS
Oil RHLB for o/w RHLB for w/o
Cottonseed oil 6-7 
Petrolatum 8 
Beeswax 9-11 5
Paraffin wax 10 4
Mineral oil 10-12 5-6
Methyl silicone 11 
Lanolin, anhydrous 12-14 8
Carnauba wax 12-14 
Lauryl alcohol 14 
Castor oil 14 
Kerosene 12-14 
Cetyl alcohol 13-16 
Stearyl alcohol 15-16 
Carbon tetrachloride 16 
Lauric acid 16 
Oleic acid 17

Stearic acid 17
Example: Formula of an emulsion is as follows:
Ingredient Amount RHLB (o/w)
1. Beeswax 15g 9
2. Lanolin 10g 12
3. Hard paraffin wax 20g 10
4. Cetyl alcohol 5g 15
5. Emulsifier 2g
6. Preservative 0.2g
7. Color q.s.
8. Water, purified q.s. 100g

To calculate the overall RHLB of the emulsion the following calculation is carried out:
Oil Phase Amount (Amount/Total)xRHLB
1. Beeswax 15g (15/50)x9 = 2.7
2. Lanolin 10g (10/50)x12 = 2.4
3. Paraffin 20g (20/50)x10 = 4.0
4. Cetyl alcohol 5g (5/50)x15 = 1.5
Total 50g 10.6
Next, a blend of two emulsifiers is chosen, one with an HLB above 10.6 and the other below 10.6. Let these two
surfactants be Tween80 (HLB = 15) and Span 80 (HLB = 4.3). These two surfactants should be mixed in such a
ratio that the mixture will have a HLB of 10.6. By aligation method:
HLB of Tween80 Parts of Tween80 15 6.3
RHLB 10.6
HLB of Span80 Parts of Span80 4.3 5.6
Required amount of Tween80 = {6.3/(6.3+5.6)}x Total amount of emulsifier
= 0.53x2 g
= 1.06 g
Required amount of Span80 = {5.6/(6.3+5.6)}x Total amount of emulsifier
= 0.47x2 g
= 0.94 g
Therefore, using 1.06 g Tween80 and 0.94 g of Span 80 we can stabilize the above formula of an
emulsion.
Choice of hydrophilic colloids

The naturally occurring gums and synthetic hydrophilic polymers are used as either primarily or (mainly)
auxiliary emulsifiers.
Mode of action
(i) They do not reduce the surface tension but forms a rigid film on the oil droplets and form
a stable o/w emulsion  thus inhibits coalescence of droplets.
(ii) As an auxiliary emulsifier they increase the viscosity of the continuous phase so that
movement of dispersed phase is reduced.
Examples:
(i) Plant origin: Acacia, tragacanth, alginates, chondrus and pectin.
(ii) Animal source: Gelatin, egg yolk, casein, woolfat, cholesterol and lecithin.
(iii) Synthetic: Methyl cellulose, Hydroxyethyl cellulose, Polyoxyethylene polymer and Carboxyvinyl
polymer.
The natural gums exhibit some type of incompatibility or instability depending on the presence of various cations,
on pH, or on a second hydrophilic polymer.
Choice of finely divided solid particles

The compounds most frequently used in pharmacy are the colloidal clays: bentonite (aluminium silicate)
and veegum (magnesium aluminium silicate). They act as good emulsifiers, especially in combination with
surfactants or viscosity building agents.
Mode of action
(i) They tend to absorb at the oil-water-interface and form thick impenetrable
films.
(ii) Sometimes increases the viscosity of water (as continuous phase).
Generally finely divided solids are used in conjunction with a surfactant to prepare
o/w emulsions but both o/w and w/o preparations can be prepared by adding the
clay to the external phase first.
They are used frequently for external purposes such as lotion or cream.

Specific formulation consideration: Consistency

Once the desired emulsion and emulsifiers have been chosen, a consistency that provides the desired
stability and yet has the appropriate flow characteristics must be attained.
The sedimentation or creaming rate of suspended spherical particles is inversely proportional to the
viscosity in accordance with Stoke’s law.
Since emulsions should flow or spread easily and since higher viscosity favors stability  so Thixotropy
in an emulsion is desirable (Thixotropy = phenomenon in which the viscosity of a preparation is reduced by
agitation but increases after agitation has been stopped.
Viscosity of emulsions responds to the following changes:
1. When the viscosity of the continuous phase is increased the viscosity of emulsion is also increased.
o/w emulsion: Viscosity of water is increased by using gums, clays and viscosity building agents.
w/o emulsion: Viscosity of oil is increased by addition of polyvalent metal soaps or the use of high
melting waxes and resins.
2. The greater the volume of internal phase, (i.e. greater phase volume ratio) the greater is the apparent
viscosity.
3. The viscosity and stability of an emulsion is increased by reducing the size of droplets and by formation of
floccules or clumps.
4. It is routinely observed that viscosity of emulsions increases upon aging. Hence, it is recommended that a
newly formulated emulsion be allowed to rest undisturbed for 24 hours before checking its viscosity.
Choice of an antimicrobial preservative

Sources of contamination:
(i) Contaminated raw materials
(ii) Poor sanitation during preparation
(iii) Contamination by the end users
Substrates of contamination:
(i) Mainly the water phase is a good medium for microbial growth.
(ii) Some ingredients, such as carbohydrates, pectin, proteins, sterols, and phosphates readily supports the
growth of a variety of microorganisms.
Remedies:
(i) Use of uncontaminated raw materials
(ii) Careful and through cleaning of equipment with steam.
(iii) Addition of preservatives
Preservatives commonly used:
Chlorocresol, chlorobutanol, mercurials [e.g. phenyl mercuric nitrate (PMN), phenyl mercuric acetate
(PMA), esters of parahydroxy benzoate (methyl, propyl, butyl, benzyl paraben), sodium benzoate, sorbic acid
etc.
[For more details see Lieberman & Lachman, Industrial Pharmacy, 3rd Edn. pp 521.]
Since microorganisms can reside in the water or the lipid phase or both, the preservative should be
available at an effective level in both phases. So it is advisable to add an oil soluble and an water soluble
preservative simultaneously.
A good example is methyl and propyl paraben. In this case methyl paraben is soluble in water while propyl and
higher esters are almost water-insoluble.
Preservatives sometimes interact with some ingredients. e.g. phenolic preservatives are especially
susceptible to interaction with compounds containing polyoxyethylene groups. Sometimes preservatives are
solubilized by the surfactants. The bound or complexed or solubilized preservative can not act as preservative.
Choice of antioxidants
The inclusion of an antioxidant in an emulsion formulation may be necessary to protect, not only an
active ingredient but also formulation components (e.g. unsaturated lipids) which are oxygen labile.
Oxidation occurs spontaneously under mild conditions generally involved some free radical reactions.
Kinetic measurements of fat oxidation in o/w emulsions indicate that the rate of oxidation is dependent on
(i) the rate of oxygen diffusion in the system,
(ii) oxygen pressure (i.e. oxygen content)

(iii) trace element of metal such as Cu, Mn, or Fe or their ions may catalyze the oxidative reactions. Thus the use
of chelating agents, in a formulation may markedly improve product stability.
(iv) Some oxidative degradation is pH dependent. So the pH stability profile of the drug and of protective
formulation should be established during product development.
List of selected antioxidants for emulsion system:

1. Chelating agents e.g. Citric acid
EDTA (Ethylene diamine tetraacetic acid)
Phenyl alanine
Phosphoric acid (H3PO4)
Tartaric acid
2. Preferentially oxidized compounds (Reducing agents)
e.g. Ascorbic acid
Sodium sulphite (Na2SO3)
Sodium bisulfite (NaHSO3)
Sodium metabisulfite (Na2S2O5)
3. Chain terminators
Water soluble compounds e.g. Cystine hydrochloride
Thioglycerol
Thioglycollic acid
Thiosorbitol
Lipid soluble compounds e.g. Alkyl gallates (octyl, propyl, dodecyl)
Butylated hydroxy toluene (BHT)
Butylated hydroxy anisole (BHA)
-tocopherol (Vit-E)
Hydroquinone
Deaeration
The formulator may wish to deaerate the system by :
(i) bubbling N2 gas through the liquids to remove dissolved O2.
(ii) boiled before use
(iii) exposure to vacuum during ultrasonic agitation
(iv) the end space above the container can be flushed with N2 just before sealing.
Reducing agents: e.g. Ascorbic acid (Vit-C)

Sulphites etc.
They preferentially get oxidized before the oxidation of oil takes place.
Uses:
(i) BHA, BHT, Vit-E and the alkyl gallates are particularly popular in pharmaceuticals and cosmetics.
(ii) BHA and BHT have a pronounced odour and should be added at low concentration.
(iii) Alkyl gallates have a better taste.
(iv) L-tocopherol (Vit-E) is well suited for edible or oral preparations, such as those containing Vitamin A.
(v) Some trace metals like copper, iron, manganese ions catalyze the auto-oxidation reaction; therefore, a small
amount of sequestering agents like citric acid, EDTA, tartaric or phosphoric acid reduce the reaction rate.
PREPARATION
 After the purpose of the emulsions has been determined, i.e oral or topical use,
 and the type of emulsions, o/w or w/o,
 and appropriate ingredients selected
 and the theory of emulsification considered
Experimental formulations may be prepared by a method suggested by Griffin.
Experimental method
1. Group the ingredients on the basis of their solubilities in the aqueous and nonaqueous phase.
2. Determine the type of emulsion required and calculate an approximate HLB value
3. Blend a low HLB emulsifier and a high HLB emulsifier to the calculated value
[N.B. For experimental formulations, use a higher concentration of emulsifier (e.g. 10 to 30% of the oil
phase) than that required to produce a satisfactory product.
4. Dissolve the oil-soluble ingredients and the emulsifiers in the oil. Heat, if necessary, to approximately 5 to
100C over the melting point of the highest melting ingredient of to a maximum temperature of 70 to 800C.
5. Dissolve the water-soluble ingredients (except acids and salts) in a sufficient quantity of water. Heat the
aqueous phase to a temperature which is 3 to 50C higher than that of the oil phase.
6. Add the aqueous phase to the oily phase with suitable agitation.
7. If acids or salts are employed, dissolve them in water and add the solution to the cold emulsion.
8. Examine the emulsion and make adjustments in the formulation if the product is unstable.
Large scale industrial method

The preparation of an emulsion requires work to reduce the internal phase into small droplets and
disperse them throughout the external phase. This can be accomplished by a mortar and pestle or a high speed
emulsifier. The addition of emulsifying agents not only reduces this work but also stabilizes the final emulsion.
Emulsions may be prepared by four principle methods:
1. Addition of internal phase to external phase
Let us take a model of o/w emulsion.
(i) The water soluble substances are dissolved in water and the oil soluble substances are dissolved in oil.
(ii) The oil mixture is added in portions to the aqueous preparation with agitation (in a colloid mill or
homogenizer).
N.B. Sometimes, in order to give a better shearing action during the preparation, all of the water is not mixed
with the emulsifying agent until the primary emulsion with oil is formed; subsequently, the remainder of the
water is added.
e.g. Emulsion using Gelatin-type A as the emulsifier.
Gelatin (Type A) 8g
Tartaric acid 0.6g
Flavour as desired
Alcohol 60ml
Oil 500ml
Purified water, to make 1000ml
Procedure
(i) The gelatin & tartaric acid are added to approximately 300ml water, allowed to stand for few minutes, heated
until gelatin is dissolve, then temperature is raised to 980C and this temperature is maintained for about 20
minutes. Cooled to 500C, flavor and alcohol are added and more water was added to make 500 ml.
(ii) The oil is added to the aqueous phase (i.e. external phase), and the mixture is agitated thoroughly and passed
it through a homogenizer or colloid mill.
2. Addition of the external phase to the internal phase
Let us take a model of o/w emulsion.
In this method water (external phase) is first added slowly to the oil (internal phase) to promote the formation of a
more w/o emulsion due to the presence of more oil than water. After further addition of water phase inversion to
an o/w emulsion should take place.
This method is especially successful when hydrophilic agents such as acacia, tragacanth or methyl
cellulose are first mixed with oil, effecting dispersion without wetting. Water is added and, eventually, an o/w
emulsion is formed.
e.g. Mineral oil emulsion
Mineral oil 500ml
Acacia, in very fine water 125g
Syrup 100ml
Vanillin 40mg
Alcohol 60ml
Purified water, upto 1000ml
(i) The mineral oil and acacia are mixed in a dry mortar. Purified water, 250 ml (Phase volume ratio o/w = 2: 1)
is added and the mixture triturated vigorously until an emulsion is formed.
(ii) A mixture of the syrup, 50 ml of purified water and the vanillin dissolved in alcohol are added in divided
portions with trituration
(iii) Sufficient purified water is then added to the proper volume, the mixture well and homogenized.
3. Mixing both phases after warming each

This method is use when waxes or other substances which require melting are used. The oil-soluble
emulsifying agents, oils and waxes are melted and mixed thoroughly. The water-soluble ingredients dissolved in
the water and warmed to a temperature slightly higher than the oil phase.
The oil phases are then mixed and stirred until cold. For convenience, but not necessity, the aqueous
solution is added to the oil mixture.
This method frequently is used in the preparation of ointments and creams.
e.g. An oral emulsion (o/w) containing an insoluble drug
1. Cotton seed oil 460g
2. Sulphadiazine 200g
3. Sorbitan monostearate 84g
4. Polyoxyethylene 20 sorbitan mono stearate 36g
5. Sodium benzoate 2g
6. Sweetener q.s.
7. Purified water 1000g
8. Flavor oil q.s.
Procedure
(i) Heat the first three ingredients to 500C and pass through colloid mill.
(ii) Add the next four ingredients at 500C to the first three ingredients at 650C and stirred while cooling to 450C.
(iii) Add the flavor oil and continue stirring until room temperature is reached.
4. Alternate addition of the two phases to the emulsifying agent

Model: Let us prepare an o/w type of emulsion.
(i) A portion of the oil is added to all of the oil-soluble emulsifying agents with mixing.
(ii) Equal quantity of water is added to all of the water-soluble emulsifying agents with mixing.
(iii) Aqueous solution is mixed with oil phase stirred until the emulsion is formed.
(iv) Further portions of water and oil are added alternately until the final product is formed.
N.B. The high concentration of the emulsifying agent in the original emulsions makes the initial emulsification
more likely and the high viscosity provides effective shearing actin leading to small droplets in the emulsion.
This method is often used successfully with soaps.
EQUIPMENTS
 The preparation of emulsion requires certain amount of energy to form the interface between the two phases,
and additional work must be done to stir the system to overcome the resistance to flow.
 In addition, heat often is supplied to the system to melt waxy solids and /or reduce the viscosity of the oil
phase.
Because of the variety of oils used, emulsifying agents, phase-volume ratio and the desired physical properties of
the product, a wide selection of equipment is available for preparing emulsions.
1. Mortar and pestle

It consists of a glass or porcelain mortar and a pestle.
Advantages:
(i) Small quantity emulsions can be prepared in the laboratory.
(ii) Low cost
(iii) Simplest operation among all other instruments.
Disadvantages
(i) Generally, the final particle size is considerable larger then in other equipments.
(ii) It is necessary for the ingredients to have a certain viscosity prior to trituration in order to achieve a
satisfactory shear.

2. Agitators / Mechanical stirrers

An emulsion may be stirred by means of various impellers (propellers:
produce axial movements; turbines produce radial and tangential movements)
mounted on shafts, which are placed directly into the system to be emulsified.
For low viscosity emulsions propeller type can be used but for higher viscosity
turbine type is used.
The degree of agitation is controlled by the rotational speed of impeller,
by the patterns of the liquid flow and the resultant efficiency of mixing are
controlled by the type of impeller, its position in the container, the presence of baffles, and the general shape of
the container.
Advantages:
(i) Agitators are used particularly for the emulsification of easily dispersed, low-viscosity oils.
(ii) Can be used for small-scale production and laboratory purpose.
Disadvantages:
Continuous shaking tends to break up not only the phase to be dispersed but also the dispersion medium, in this
way, impairs the ease of emulsification.
3. Colloid mill GRINDING

The principle of operation of the colloid mill is SURFACES
the passage of the mixed phases of an emulsion
formula between a stator and a high speed rotor FEED
revolving at speeds of 2000 to 18,000 rpm. ROTOR
The clearance between the rotor and the stator is
adjustable, usually from 0.001 inch upward. The
emulsion mixture, while passing between the
rotor and the stator, is subjected to a STATOR
tremendous shearing action which effects a fine
dispersion of uniform size. COOLANT
The shearing forces applied in the colloid mill OUTLET
usually raises the temperature within the COOLANT
COOLANT
emulsion. Hence, a coolant is used to absorb the INLET
excess heat.
Advantage
(i) Very high shearing force can be generated.
(ii) Very fine particles can be prepared. OUTLET
(iii) Particularly useful in preparing suspensions containing poorly wetted solids.
(iv) Useful for the preparation of relatively viscous emulsions.
4. Homogenizers
Impeller type of equipment frequently produce a satisfactory emulsion; however, for further reduction in particle
size, homogenizers may be employed.
Homogenizers may be used in one of two ways:
(i) The ingredients in the emulsion are mixed and then passed HOMOGENIZED
through the homogenizer to produce the final product. PRODUCT
(ii) A coarse emulsion is prepared in some other way and then
passed through a homogenizer for the purpose of decreasing
the particle size and obtaining a greater degree of VALVE
uniformity and stability. SEAT
The coarse emulsion (basic product) enters the valve seat at BASIC
VALVE
high pressure (1000 to 5000 psi), flows through the region PRODUCT
between the valve and the seat at high velocity with a rapid
pressure drop, causing cavitation; subsequently the mixture hits
the impact ring causing further disruption and then is IMPACT RING
discharged as a homogenized product. It is postulated that
circulation and turbulence are responsible mainly for the homogenization that takes place.
Sometimes a single homogenization may produce an emulsion which, although its particle size is small, has a
tendency to clump of form clusters. Emulsions of this type exhibit increased creaming tendencies. This is
corrected by passing the emulsion through the first stage of homogenization at a high pressure (e.g. 3000 to 5000
psi) and then through the second stage at a greatly reduced pressure (e.g. 1000 psi). This breaks down any
clusters formed in the first step (it is a two stage homogenizer).
5. Ultrasonic devices
The preparation of emulsions by the use of ultrasonic vibrations also is possible. An oscillator of high frequency
(100 to 500 kHz) is connected to two electrodes between which placed a piezoelectric quartz plate. The quartz
plate and electrodes are immersed in an oil bath and, when the oscillator is operating, high-frequency waves flow
through the fluid. Emulsification is accomplished by simply immersing a tube containing the emulsion ingredients
into this oil bath.
Advantages
Can be used for low viscosity and extremely low particle size.
Disadvantages
Only in laboratory scale it is possible. Large scale production is not possible.
Example: Pohlman Whistle

Commercial products may be prepared using
ultrasonics based upon the device known as the Pohlman
whistle. In this apparatus, the premixed liquids are forced
through a thin orifice and are allowed to impinge upon the
free end of a knife-edge bar which is made to vibrate.
Ultrasonic waves are produced and areas of
compression and rarefaction are formed. Shock waves are
produced by the collapse of bubbles which produced a shear
effect, thereby producing fine particle sizes.
STABILITY OF EMULSION
The stability of an emulsion must be considered in terms of physical stability of emulsion system and the
physical and chemical stability of the emulsion component including pharmacologically active ingredients, if any.
Definition: A physically stable emulsion component may be defined as a system in which the globules
retain their initial character and remain uniformly distributed throughout the continuous phase.
Symptoms of instability
As soon as an emulsion has been prepared, time and temperature dependent processes occur to effect its
separation. During storage, an emulsion’s stability is evidenced by (i) creaming, (ii) flocculation and / or (iii)
coalescence.
CREAMING
Creaming is the upward or downward movement of dispersed droplets related to the continuous phase due to the
difference of density between two phases.
N.B. The downward creaming is also called sedimentation. Generally the term “sedimentation” is associated with the
downward movement of solid particles in suspension.
Creaming is undesirable in a pharmaceutical product where homogeneity is essential for the administration of
correct and uniform dose. It may still be pharmaceutically acceptable as long as it can be reconstituted by a
modest amount of shaking. However, in case of cosmetic products creaming is usually unacceptable because it
makes the product inelegant.
Creaming or sedimentation brings the particle closer together and may facilitate a serious problem of coalescence.
The rate at which a spherical droplet or particle sediments in a liquid is governed by Stoke’s equation.
d2(1  2)g where v = velocity of creaming
v = d = diameter of globule
18 1 , 2 = densities of dispersed phase and continuous phase respectively
 = viscosity of the continuous medium
A consideration of this equation shows that the rate of creaming will be decreased by:
(i) reduction of droplet size
(ii) a decrease in the density difference between the two phases
(iii) increase in the viscosity of the continuous phase
 Reduction in droplet size is done by using an efficient homogeniser or colloid mill. There are, however,
technical difficulties in reducing the diameter of droplets to below about 0.1 m.
 Stoke’s equation predicts that no creaming is possible if the specific gravities of the two phases are equal. A
few successful attempts have been made to equalize the densities of the oil and aqueous phase. This method is
of little use in pharmaceutical practice because, it usually involves the addition of substances those are
unacceptable in pharmaceutical preparations.
 The most frequently used approach is to raise the viscosity of the continuous phase although this can be done
to the extent that the emulsion still can be removed readily from its container and spread on the body surface
conveniently.
FLOCCULATION
Flocculation of the dispersed phase may take place before, during or after
creaming.
Flocculation is reversible aggregation of droplets of the internal phase in
the form of three- dimensional clusters.
In the floccules the droplets remain aggregated but intact. The droplets can
remain intact when the mechanical or electrical barrier is sfficient to
prevent droplet coalescence.
e.g. if an insufficient amount of emulsifier is present, emulsion droplets aggregate and coalesce.
The reversibility of this type of aggregation depends on the strength of the interaction between particles, as
determined by:
(i) the chemical nature of the emulsifier,
(ii) the phase-volume ratio, and
(iii) the concentration of dissolved substances, especially electrolytes.
The viscosity of an emulsion depends to a large extent on flocculation, which restricts the movement of particles
and can produce a fairly rigid network. Agitation of an emulsion breaks the particle-particle interactions with a
resulting drop of viscosity; i.e. shear thinning.
COALESCENCE
Coalescence is a growth process during which the emulsified particles join to form larger particles.
Any evidence for the formation of larger droplets by merger of smaller droplets suggests
that the emulsion will eventually separate completely.
The major factor which prevents coalescence in flocculated and deflocculated emulsions is
the mechanical strength of the interfacial barrier. Thus macromolecules and particulate
solids forms thick interfacial film  and hence natural gums and proteins are useful as auxiliary emulsifiers when
used at low level, but can even be used as primary emulsifiers at higher concentrations.
Any agent that will destroy the interfacial film will crack the emulsion. Some factors are:
(i) the addition of a chemical that is incompatible with the emulsifying agent. Examples include surfactants of
opposite ionic charges, addition of large ions of opposite charge, addition of electrolytes such as Ca and Mg
salts to emulsions stabilized with anionic surfactants.
(ii) Bacterial growth: Protein materials and non-ionic surfactants are excellent media for bacterial growth.
(iii) Temperature change: Protein emulsifying agent may be denatured and the solubility characteristics of non-
ionic emulsifying agents change with a rise in temperature. Heating above 700C destroys almost all
emulsions. Freezing will crack an emulsion; this may be due to the ice-crystals disrupting the interfacial film
around the droplet.
EVALUATION OF EMULSION
SHELF LIFE
The final acceptance of an emulsion depends on stability, appearance, and functionality of the packaged product.
There is no quick and sensitive methods for determining potential instability in an emulsion are available to the
formulator. To speed up the stability test program the emulsion is subjected to various stress conditions.
The stress conditions normally employed include:
(i) aging and temperature
(ii) centrifugation, and

(iii) agitation
Aging and temperature
It is routine to determine the shelf life of all types of preparations by storing them for varying periods of time at
temperatures that are higher than those normally encountered. A particularly useful means of evaluating shelf life
is cycling between two temperatures preferably between 40 and 450C.
The normal effect of aging an emulsion at elevated temperature is acceleration of the rate of coalescence or
creaming, and this is usually coupled with changes in viscosity.
Centrifugation
Stoke’s law shows that creaming is a function of gravity (g), and an increase in gravity therefore accelerates
separation. Centrifugation at 3750 rpm in a 10-cm radius centrifuge for a period of 5 hours is equivalent to the
effect of gravity for about one year. Thus shelf-life under normal storage conditions can be predicted rapidly by
observing the separation of the dispersed phase due to either creaming or coalescence when the emulsion is
exposed to centrifugation.
Agitation
Droplets in an emulsion exhibit Brownian movement. Coalescence takes place when droplets impinge upon each
other. Simple mechanical agitation contributes to the energy with which two droplets impinge upon each other.
Thus agitation can also break emulsion. A typical case is the manufacture of butter from milk.
Conventional emulsions may deteriorate from gentle rocking on a reciprocating shaker. This works in two ways:
(i) increases the rate of impingement of droplets, and
(ii) Reduction of viscosity of a normally thixotrophic system.
PHYSICAL PARAMETERS
The most useful parameters commonly are measured to assess the effect of stress conditions on emulsions include
1. phase separation,
2. viscosity,
3. electrophoretic properties, and
4. Particle size analysis and particle count.
PHASE SEPARATION
The rate and extent of phase separation after aging of an emulsion may be observed visually or by measuring the
volume of separated phase.
A simple means of determining phase separation due to creaming or coalescence involves withdrawing a samples
of the emulsion from the top and the bottom of the preparation after some period of storage and comparing the
composition of the two samples by appropriate analysis of water content, oil content, or any suitable constituent.
VISCOSITY
The viscosity of an emulsion for the use of shelf studies is not concerned with absolute values of viscosity, but
with changes in viscosity during aging. Since emulsions are generally non-Newtonian systems and the viscosity is
measured by viscometer of the cone-plate type are particularly useful for emulsions, but instruments utilizing co-
axial cylinders (e.g. cup and bob viscometer) are the easiest to use. The use of a penetrometer is often helpful in
detecting changes of viscosity with age.
In case of w/o emulsions flocculation is quite rapid. After flocculation viscosity drops quickly and continues to
drop for some time (5 to 15 days at room temperature).
In case of o/w emulsions globule flocculation causes an immediate increase in viscosity. After this initial change,
almost all emulsions show changes in viscosity with time which follow a linear relationship when plotted on a
log-log scale.
A practical approach for the detection of creaming or sedimentation, before it becomes visibly apparent, utilizes
the Helipath attachment of the Brookfield viscometer
N.B. The Brookfield viscometer determines the resistance encountered by rotating spindle or cylinder immersed in a
viscous material. The Helipath attachment slowly lowers the rotating spindle into the medium so that the resistance
measured is always that of previously undisturbed test substances.
As a result of emulsion separation, the descending rotating spindle meet varying resistance at different levels and
registers fluctuations in viscosity.

Example
Lotion A in the figure contains solids suspended in an emulsion,
and the high viscosity near the top is due to non-wetted solid and
creamed emulsion; the high viscosity at the lower level is due to
sedimented particles.
The addition of polyoxyethylene monooleate (SAA) and methyl
cellulose (viscosity enhancer) in lotion B yields a much more
uniform viscosity pattern after eight weeks storage.
ELECTROPHORETIC PROPERTIES
If the instability of the emulsion is due to flocculation only (and
not due to coalescence) then the zeta potential will have to be measured.
Zeta potential can be determined with
(i) the aid of the moving boundary method or
(ii) more quickly and directly, by observing the movement of particles under the influence of electric current.
The zeta potential is especially useful for assessing flocculation since electrical charges on particles influence the
rate of flocculation.
The measurement of electrical conductivity has been claimed to be a powerful tool for the evaluation of emulsion
shortly after preparation.
PARTICLE SIZE NUMBER ANALYSIS

Changes of the average particle size or of the size distribution of droplets are important parameters for evaluating
emulsions.
Particle size determination can be carried out by microscopic method pr by electronic counting machines. (e.g.
Coulter counter). Light scattering and related reflectance relationships have been used for particle size
determination.
The utility of particle size for predicting or interpreting emulsion shelf-life is somewhat doubtful.
Practical recommendation for shelf-life prediction in temperate (hot and humid) zone
A typical test program for an “acceptable: emulsion (in temperate zone) may be as follows:
The emulsion should be stable with no visible signs of separation for at least:
(i) 60 to 90 days at 45 or 500C,
(ii) 5 to 6 months at 370C and
(iii) 12 to 18 months at room temperature.
(iv) After 1 month storage at 40C
(v) After 2 to 3 freeze-thaw cycles between 20 and +250C.
(vi) After 6 to 8 freeze-thaw cycles between 4 and 450C with storage at each temperature for not less than 48
hours.
(vii)No deterioration by centrifuging at 2000 to 3000 rpm at room temperature.
(viii)No deterioration by agitation for 24 to 48 hours on a reciprocating shaker ( 60 cycles per minute) at room
temperature and at 450C.

PHARMAROCKS GPAT SUCCESS TEST SERIES-2016 SUSPENSION
SUSPENSION
Syllabus:
Definition, general formulation with example, suspending agents, preservatives,
vehicles, stabilizers, colorants, flavoring agents and such other components,
processing and equipment.
Questions:
1. Define and differentiate between solution and suspension
2. Give the importance of suspending agents in pharmaceutical dosage forms.
Discuss the different methods of formation of suspensions
3. How do you evaluate the stability of a suspension? What are structured
vehicles? How do they help in increasing the stability of a suspension? Mention
any two materials which help in improving the stability of suspension with a
brief explanation.
4. Write an account of an ideal suspending agent and stabilizer used in suspension.
5. Define suspensions. Describe the formulation of a suspension.
DEFINITION
A suspension is a two phase system composed of a solid material dispersed in a liquid. The
liquid can be oily or aqueous. However, most suspensions of pharmaceutical interest are
aqueous.
ADVANTAGES
Suspensions offer distinct advantages _ they are as follows:

1. Stability: Some drugs are not stable in solution form. In such cases it is necessary to
prepare an insoluble form of that drug. Therefore drugs are administered in the form of
suspension. e.g. Procaine Penicillin G.
2. Choice of solvent: If the drug is not soluble in water and solvents other than water are not
acceptable, suspension is the only choice. e.g. Parenteral corticosteroid.

3. Mask the taste; In some cases drugs are made insoluble and dispensed in the form of
suspension to mask the objectionable taste. e.g. Chloramphenicol base is very bitter in
taste, hence the insoluble chloramphenicol palmitate is used which does not have the bitter
taste
4. Prolonged action: Suspension has a sustaining effect, because, before absorption the solid
particles should be dissolved. This takes some time. e.g. Protamine Zinc Insulin and
procaine penicillin G.
5. Bioavailability: Drugs in suspension exhibit a higher bioavailability compared to other
dosage forms (except solution) due to its large surface area, higher dissolution rate. e.g.
Antacid suspensions provides immediate relief from hyperacidity than its tablet chewable
tablet form.
TYPES OF SUSPENSIONS
The pharmaceutical suspension preparations are differentiated into suspensions, mixtures,

magmas, gels and lotions.
Suspensions
Simple suspension is the insoluble solid dispersed in a liquid. The stability considerations
suggest that the manufacture of drugs in dry form is ideal. They are reconstituted as
suspensions using a suitable vehicle before administration.
Few examples are:
i) Dispersible tablets of antibiotic, amoxycillin (e.g. PRESSMOX)
ii) Procaine penicillin G powder (E.G. PENIDURE)
Gels
Gels are semisolid systems consisting of small inorganic particles suspended in a liquid
medium. It consists of a network of small discrete particles. It is a two-phase system. e.g.
Aluminum hydroxide gel.
Lotions
Lotions are suspensions which are intended to be applied to the unbroken skin without
friction. e.g. Calamine lotion, hydrocortisone lotion.

Magmas and Milks
Magmas and milk are aqueous suspensions of insoluble, inorganic drugs and differ from gels
mainly in that the suspended particles are larger. when prepared they are thick and viscous and
because of this, there is no need to add a suspending agent. e.g. Bentonite magma, milk of
magnesia.
Mixtures
Mixtures are oral liquids containing one or more active ingredients, dissolved, suspended or
dispersed in a suitable vehicle. Suspended solids may separate slowly on standing, but are
easily redispersed on shaking. e.g. Kaolin mixture with pectin.
CLASSIFICATION OF SUSPENSIONS
Based on the proportion of solids, suspensions are empirically classified as dilute or

concentrated systems.
i) Dilute suspensions : Solid content 2 - 10 % e.g. Cortisone acetate and prednisolone
acetate suspension.
ii) Concentrated suspensions: Solid content 10 - 50 % e.g. Zinc oxide suspension for
external use, Procaine penicillin G injection, Antacid suspension etc.
Depending on the nature and behavior of solids suspensions are classified as flocculated and
deflocculated.
DEFLOCCULATED SUSPENSION
In this system, solids are present as individual particles.
FLOCCULATED SUSPENSION
In this system, particles aggregate themselves by physical bridging. These

flocs are light, fluffy conglomerate which are held together by weak van der
Waal’s forces of attraction.
If the aggregate is an open network it is called floccule. They are fibrous,
fluffy, open network of particles. It is loosely packed after sedimentation.
If the aggregate is a closed one - it is called coagule. They are tightly
packed, produced by surface film bonding.

TABLE: COMPARISON BETWEEN DEFLOCCULATED AND FLOCCULATED SYSTEM

DEFLOCCULATED SYSTEM FLOCCULATED SYSTEM
i) Pleasant appearance, because of uniform i) Somewhat unsightly sediment.
dispersion of particles.
ii) Supernatant remains cloudy. ii) Supernatant is clear
iii) Particles exist as separate entities iii) Particles form loose aggregates.
iv) Rate of sedimentation is slow, as the size iv) Rate is high, as flocs are the collection
of particles are small. of smaller particles having a larger
v) Particles settle independently and size.
separately v) Particles settle as flocs.
vi) The sedimentation is closely packed and vi) Sediment is a loosely packed network
form a hard cake. and hard cake cannot form.
vii) The hard cake cannot be redispersed. vii) The sediment is easy to redisperse.
viii)Bioavailability is higher due to large viii)Bioavailability is comparatively less
specific surface area. due to small specific surface area.
FACTORS AFFECTING THE STABILITY OF A SUSPENSION
SETTLING IN SUSPENSIONS
Brownian movement
Brownian movement of particles prevents sedimentation. In general, particles are not in a state
of Brownian motion in pharmaceutical suspensions, due to
i) larger particle size (Brownian movement is seen in particles having diameter of about 2 to
5 m (depending on the density of the particles and the viscosity and the density of the
suspending medium.
ii) and higher viscosity of the medium.
Sedimentation
The rate of sedimentation of particles can be expressed by the Stoke’s law, using the following
formula:

d 2 (  s l ) g
Se dim entationrate 
18
Where d is the particle diameter

s,  l are densities of a particle and liquid respectively.
g is the acceleration of gravity.
 is the viscosity of the medium.
Stock’s law is applicable if:
i) Particles are spherical; but particles in the suspension are largely irregular.
ii) Particles settle freely and independently.
In suspensions containing 0.5 - 2 % (w/v) solid, the particles do not interfere with each other
during sedimentation - hence free settling occurs.
Most pharmaceutical suspensions contain 5 - 10 % or higher percentages of solid. in this cases
particles interfere with one another as they fall - hence hindered settling occurs and Stoke’s
law no longer applies.
Stoke’s law is applicable to deflocculated systems, because particles settle independently.
However, this law is useful in a qualitative manner in fixing factors which can be utilized in
formulation of suspensions.
1. Particle size
Rate of sedimentation  (diameter of particle)2

So smaller the particle size more stable the suspension. The particle-particle interaction results
in the formation of floccules or coagules where the sedimentation rate increases. The particles
are made fine either by dry milling prior to suspension or wet-milling of the final suspension
in a colloid mill or a homogenizer.
2. Viscosity of the medium
According to Stoke’s law:

Rate of sedimentation  1 / (viscosity of the medium)
The viscosity of suspension should be optimum. Viscosity can be increased by adding
suspending agents or thickening agents. selection of high viscosity have both advantages and
disadvantages.
Advantages
i) Sedimentation rate is retarded, hence enhances the physical stability of the suspension.

ii) Inhibits crystal growth, because movement of particles is diminished.

iii) Prevents the transformation of metastable crystals to stable crystals.
Disadvantages
i) Redispersibility of the suspension on shaking is difficult.
ii) Pouring out of the suspension from the container may be difficult.
iii) Creates problems in the handling of materials during manufacture.
iv) May retard absorption of drugs from the suspension.
3. Density
Rate of sedimentation  (density of solid  density of liquid medium)

Lesser the difference between the densities of solid particles and liquid medium slower
is the rate of sedimentation. Since it is very difficult to change the absolute density of the solid
particles so the density of the liquid medium can be manipulated by changing the composition
of the medium. The addition of nonionic substances such as sorbitol, polyvinylpyrrolidone
(PVP), glycerin, sugar, or one of the polyethyleneglycols or combination of these may be
helpful in the manipulation.
If the density of the particles is greater than the continuous medium the particles will
settle downwards, the phenomenon is known as sedimentation. If the density of particle is
lesser than that of the liquid medium then the particles will move upward - the phenomenon is
known as creaming.
FORMULATION OF SUSPENSIONS
The product must

1) Flow readily from the container
2) Possesses a uniform distribution of particles in each dose.
Two approaches are commonly employed to secure the two requirements,
(i) the use of structured vehicle t maintain deflocculated particles in suspension. Structured
vehicles are pseudoplastic and plastic in nature; it is frequently desirable that thixotropy be
associated with these two type of flow. Structured vehicles act by entrapping the particles
so that, ideally no settling occurs. In reality some degree of sedimentation will usually take
place. The shear thinning property of these vehicle does however facilitate the
redispersion when shear is applied.
(ii) and the application of the principles of flocculation to produce flocs that, although, they
settle rapidly are easily redispersed with a minimum of agitation.
WETTING OF PARTICLES
The initial dispersion of an insoluble powder in a vehicle is an important step in the

manufacturing process. Powders sometimes are added to the vehicle, particularly in large scale
operations, by dusting on the surface of the liquid. It is frequently difficult to disperse the
powder owing to an adsorbed layer of air, minute quantity of grease and other contaminants.
Powders those are not easily wetted by water and accordingly show a large contact angle,
such as sulfur, charcoal and magnesium stearate are said to be hydrophobic. Powders those
are readily wetted by water when free of adsorbed contaminants are called hydrophilic. e.g.
zinc oxide, talc, magnesium carbonate etc. belong to this category.
When a strong affinity exists between a liquid and a solid, the liquid easily forms a film over
the surface of the solid. When this affinity is non-existent or weak, the liquid faces difficulty in
displacing the air or other substances surrounding the solid.
Hydrophilic solids usually can be incorporated into suspensions without the use of a wetting
agent, but hydrophobic materials are extremely difficult to disperse and frequently float on the
surface of the fluid owing to poor wetting of the particles or the presence of tiny air pockets
on the surface of the solid particles.
To reduce the contact angle between solid and liquid (i.e. increase the wettability) the
following agents can be tried out:
1. Surfactants Solid-liquid interfacial tension is reduced by incorporating a surfactant
with a HLB value between 7 to 9. These are employed to allow the displacement of air
from hydrophobic material and permit the liquid, to surround the particles and provide a
proper dispersion. The surfactant is mixed with the solid particles if required by shearing.
The hydrocarbon chain is preferentially adsorbed to the hydrophobic surface, with the
polar part of the surfactant being directed towards the aqueous phase.
2. Hydrophilic polymers such as sodium carboxymethyl cellulose, certain water-insoluble
hydrophilic material such as bentonite, aluminum-magnesium silicates, and colloidal silica,
either alone or in combination can be incorporated in desired concentration. These
materials are also used as suspending agents and may produce a deflocculated system
particularly if used at low concentration.
3. Solvents such as alcohol, glycerol and glycols which are water miscible will reduce the
liquid / air interfacial tension. The solvent will penetrate the loose agglomerates of powder

displacing the air from the pores of the individual particles thus enabling wetting by
dispersion medium.
Method of selection of a suitable wetting agent
In order to select a suitable wetting agent Heistand has used a narrow trough, several inches
long and made of a hydrophobic material, such as Teflon, or coated with paraffin wax. At one
end of the trough is placed the powder and the other end the solution of the wetting agent.
The rate of penetration of the wetting agent solution into the powder can then be observed
directly. Greater the rate of penetration of the solution into the powder better is the wetting
property of the solution.
RHEOLOGIC CONSIDERATIONS
Rheologic consideration are important in

(i) the viscosity of a suspension as it affects the settling of particles. As viscosity increases
rate of sedimentation of the particles reduces.
(ii) the change in flow properties of the suspension when the container is shaken and when the
product is poured out off the bottle.
(iii) the spreading quality of the lotion when applied to the affected area.
(iv) during the manufacture of the suspensions.
Importance of suspending agents
 The particles in a suspensions are experiencing bombardment constantly with each

other owing to the Brownian movement.
 During this type of inter-particular interaction the particles may circumvent the
repulsive force between them and form larger particles which will then settle rapidly.
 Suspending agents reduce this movement of the particles by increasing the viscosity of
the medium.
 According to Stoke’s law rate of sedimentation is inversely proportional to the
viscosity of medium. So the settling of the particles, either in flocculated or
deflocculated system, can be slowed down by increasing the drag force on the moving
particles by increasing the viscosity of the medium.
 Hydrophilic polymers such as sodium carboxymethyl cellulose, certain water-insoluble
hydrophilic material such as bentonite, aluminum-magnesium silicates, and colloidal

silica, either alone or in combination can be incorporated in low concentration as

wetting agent.
 Hydrophilic polymers also acts as protective colloids and particles coated in this
manner are less prone to cake than are uncoated particles.
Cellulose polymers
 Sodium carboxymethyl cellulose SCMC
 Methylcellulose MC
 Hydroxy propyl methylcellulose. HPMC
Proteins e.g. gelatin.
Synthetic polymer e.g. Polyacrylic acid (Carbopol)
Clays essentially hydrated aluminum and/or magnesium silicates are also useful in suspension
formulation.
Characteristics of ideal suspending agent
(i) An ideal suspending agent should have a high viscosity at negligible shear; i.e. during shelf
storage; and it should have a low viscosity at high shear rates, i.e. it should be free flowing
during agitation, pouring and spreading on the skin.
(ii) Suspending agents should coat the particles which will be less prone to caking than the
uncoated particles.
 Pseudoplastic substances e.g. tragacanth, sodium alginate and sodium
carboxymethylcellulose show these desirable qualities.
 It is a shear thinning system, i.e. when this type of system is shaken or agitated the
viscosity diminishes.
 A suspending agent that is thixotropic as well as pseudoplastic should prove to be
useful since it forms gel on standing and becomes fluid when disturbed.
E.g. Bentonite - Carboxymethylcellulose has both pseudoplastic and thixotropic behavior.
Suspending agent Concentration in which generally used

Sodium carboxymethyl cellulose (SCMC) 0.5  2.5 %
Tragacanth 1.25 %
Guargum 0.5 %
Carbopol 934 0.3 %

CONTROLLED FLOCCULATION
Assuming that the powder is properly wetted and dispersed attention may now be given to the
various means by which controlled flocculation may be produced so as to prevent compact
sediment which is difficult to redisperse.
Controlled flocculation can be described in terms of the materials used to produce flocculation
I suspensions, namely, (i) electrolytes, (ii) surfactants, and (iii) polymers.
(i) Electrolytes act as flocculating agents by reducing the electric barrier between the
particles, as evidenced by a decrease in the zeta-potential and formation of a bridge between
adjacent particles so as to link them together in a loosely arranged structure.
Example:
 When bismuth subnitrate is suspended in water it has been found (by electrophoretic
studies) that they possess a large positive charge, or zeta potential. Because of the
strong forces of repulsion between adjacent particles, the system remains in
deflocculated (peptized) state.
 The addition of monobasic potassium phosphate (KH2PO4) to the suspension causes
the positive zeta-potential to decrease owing to the adsorption of the negatively
charged phosphate anion. The particles then can come closer to form aggregates.
 On further addition of KH2PO4 the zeta potential eventually falls to zero and then
increases in a negative direction.
 Microscopic examination of the various suspensions shows that at a certain positive
zeta potential, maximum flocculation occurs and will persist until the zeta potential has
become sufficiently negative for deflocculation to occur once again.
 The onset of flocculation coincides with the maximum sedimentation volume
determined. F remains reasonably constant while flocculation persists, and only when
the zeta potential becomes sufficiently negative to effect deflocculation.
(ii) Surfactants both ionic and nonionic, have been used to bring about flocculation of
suspended particles. The concentration necessary to achieve this effect would appear to be
critical since these compounds may also act as wetting agents to achieve dispersion.
(iii) Polymers are long chain, high molecular weight compounds containing active groups
spaced along their length. These agents act as flocculating agents because part of the chain is
adsorbed on the particle surface, with the remaining parts projecting out into the dispersion
medium. Bridging between these latter portions leads to the formation of flocs.
Hydrophilic polymers also acts as protective colloids and particles coated in this manner are
less prone to cake than are uncoated particles.
FLOCCULATION IN STRUCTURED VEHICLE
Although the controlled flocculation approach is capable of fulfilling the desired physical
chemical requisites of a pharmaceutical suspension, the product can look unsightly if F, the
sedimentation volume, is not close to or equal to 1.
So a suspending agent is added to retard sedimentation of the flocs. Such agents as
carboxymethylcellulose (CMC), Carbopol 934, Veegum, tragacanth or bentonite have been
employed, either alone or in combination.
These may lead to incompatibilities, depending on
(i) the initial particle charge
(ii) the charge carried by flocculating agent and
(iii) the charge carried by suspending agent.
PREPARATION OF SUSPENSIONS
Method of preparations can be subdivided into two broad categories:
Precipitation method
There are three methods

1. organic solvent precipitation
2. precipitation effected by changing the pH of the medium and

3. double decomposition
(i) Organic solvent precipitation
Water insoluble drugs can be precipitated by dissolving them in water-miscible organic
solvents (e.g. alcohol, acetone, propylene glycol and polyethylene glycol) and then adding the
organic phase to distilled water under standard conditions produces a suspension having a
particle size in the 1 to 5 m range.
Example: Prednisolone is precipitated from a methanolic solution to produce a suspension in
water.
Disadvantage: Harmful organic solvents may be difficult to remove.
Advantage: In case of parenteral or inhalation therapy very fine particles are
required, which can be prepared by this method.
(ii) Precipitation effected by changing the pH of the medium
A drug may be readily soluble at a certain pH and precipitate at another pH. This type of drug
is first dissolved in the favorable pH and then the solution is poured in another buffer system
to change the pH of the medium and the drug will form a suspension in the medium of the
second pH.
Example 1: Estradiol suspensions can be prepared by changing the pH of its aqueous solution;
estradiol is readily soluble in alkali as potassium or sodium hydroxide solutions.
If a concentrated solution of estradiol is thus prepared and added to a weakly acidic solution
of hydrochloric, citric or acetic acids, under proper conditions of agitation, the estradiol is
precipitated in a fine state of subdivision.
Example 2: Insulin suspension may also be prepared by pH change method.
Insulin has an isoelectric point of approximately pH5.
When it is mixed with a basic protein, such as protamine, it is readily precipitated when pH is
between the isoelectric points of the two components, i.e. pH 6.9 to 7.3. Protamine-Zinc-
Insulin (PZI) contains an excessive quantity of zinc to retard the rate of absorption.
According to the British Pharmacopoeia phosphate buffer is added to an acidified solution of
PZI so that the pH is between 6.9 to 7.3 to form the suspension.
(iii) Double decomposition method
In this method two water soluble reagent forms a water insoluble product.
Example: White Lotion NF is prepared by slowly adding zinc sulfate solution in a solution of
sulphurated potash to form a precipitate of zinc polysulphide.

Dispersion method
In this cases the powder form of the drug is directly dispersed in the liquid medium. The liquid
medium should have good power of wetting the powder.
1. Small scale preparation method
A suspension is prepared on the small scale by grinding or levigating the insoluble material in
the mortar to a smooth paste with a vehicle containing the dispersion stabilizer and gradually
adding the remainder of the liquid phase in which any soluble drugs may be dissolved. The
slurry is transferred to a graduate, the mortar is rinsed with successive portions of the
dispersion medium is finally brought to the final volume.
2. Large scale preparation method
On large scale dispersion method the solid particles are suspended using ball, pebble and
colloid mills. Dough mixers, pony mixers and similar apparatus are also employed.
EVALUATION OF SUSPENSION STABILITY
Sedimentation volume
Since redispersibility is one of the major considerations in assessing the acceptability of a

suspension, and since the sediment formed should be easily dispersed by moderate shaking to
yield a homogeneous system, measurement of the sedimentation volume and its ease of
redispersion are the two common evaluative procedures.
Definition:
The sedimentation volume, F, is defined as the ratio of the final, or ultimate volume of the
sediment (Vu), to the original volume of the suspension (Vo), before settling. Thus
F = Vu / Vo
The sedimentation volume can have values less than 1 to greater than 1.
If the volume of sediment in a flocculated system equals the original volume of suspension,
then F = 1. Such a product is said to be in ‘flocculation equilibrium’.
Procedure: The suspension is taken in a measuring cylinder upto a certain height and left
undisturbed. The particles will settle gradually. The value of F is determined from the ratio of
the volume of the sediment at that instant of time (Vu) and the original volume of the
suspension (Vo). The value of F is plotted against time (t). The plot will, will start at 1.0. at
time zero. The curve will either run horizontally or gradually sloping downward to the right as
time goes on.
One can compare different formulations and choose the best by observing the line, the better
formulation obviously producing lines that are more horizontal and/or less steep.
If the suspension is highly concentrated then the suspension is diluted with the continuous
medium (liquid phase) and then the sedimentation volume is determined.
Degree of flocculation
A more useful parameter is the degree of flocculation, .

Definition: degree of flocculation is the ratio of ultimate sediment volume of flocculated
suspension to that of a deflocculated suspension.
sedimentation volume of flocculated suspension (F)
 =
sedimentation volume of deflocculated suspension (F)
F = V / Vo F = sedimentation volume of deflocculated suspension

V = ultimate sediment volume of deflocculated suspension
Vo = original volume of suspension
F = Vu / Vo F = sedimentation volume of flocculated suspension

Vu = ultimate sediment volume of flocculated suspension
Therefore,  = F / F
 (V / Vo) / (Vu / Vo)
= (V / Vu)
ultimate sediment volume of flocculated suspension (Vu)

 =
ultimate sediment volume of deflocculated suspension (V)
Redispersibility
The evaluation of redispersibility is also important. To quantitate this parameter to some

extent, a mechanical shaking device may be used. It simulates human arm motion during the
shaking process and can give reproducible result when used under controlled conditions.

Rheologic methods
Rheologic behavior can also be used to help determine the settling behavior and the
arrangement of the vehicle and particle structural features for purposes of comparison. The
structure of the suspension changes during storage period. This structural changes can be
evaluated by rheologic method.
A practical rheologic method involves the use of a Brookfield viscometer mounted on a

helipath stand. The T-bar spindle is made to descend slowly into the suspension, and the dial
reading on the viscometer is then a measure of the resistance the spindle meets at various level
in the sediment. In this technique, the T-bar is continually changing position and measures
undisturbed samples as it advances down in the suspension This technique also indicates in
which level of the suspension the structure is greater, owing to the particle agglomeration,
because the T-bar descends as it rotates, and the bar is continually entering new and essentially
undisturbed material.
Thus using the T-bar spindle and the helipath, the dial reading can be plotted against the
number of turns of the spindle. The result indicates how the particles are setting with time. In a
screening study the better suspensions show a lesser rate of increase of dial reading with
spindle turns, i.e. the curve is horizontal for a longer period.
Electrokinetic techniques
Instrument : Microelectrophoresis apparatus.
 Such instrument permit measurement of the migration velocity of the particles with
respect to the surface electric charge or the zeta potential.
 Zeta potential correlated well with the visually observed caking and certain zeta
potential produced more stable suspensions because aggregation was controlled and
optimized.
Particle Size Changes
 During storage or transport the product may experience a fluctuation of temperature

which may lead to crystal growth or physical incompatibilities.
 Normally it may take time to check the stability regarding crystal growth.
 So to accelerate this effect freeze-thaw cycling technique is particularly applicable.

 The product is put into refrigerator and again brought into room temperature
 This type of temperature cycling promotes the growth of particle size.
 The growth of particle and size distribution are estimated by microscopic means.
Example(i) The crystal growth of sulfathiazole in suspensions is found to accelerate after
temperature cycling
Example(ii) the preservative and protective colloid, may have a profound effect on the
physical performance of a suspension under freeze-thaw conditions. Two low solid content
steroid injectable preparations of following compositions underwent freeze-thaw condition the
first preparation showed intense caking while the latter was unaffected.
Preparation Protective colloid Preservative Result after freeze-thaw

I sodium carboxy benzyl alcohol Caked badly
methylcellulose
II carboxy methyl methyl paraben, No caking
cellulose propyl paraben
Example (iii) Gelatin solidifies at low temperature and methyl cellulose is precipitates in hot water.

SEMISOLID DOSAGE
FORMS
Syllabus Topics
Ointment bases: oleaginous bases, hydrocarbon and silicon containing bases.
Absorption bases, emulsion bases, water soluble bases.
Preparation and preservation of these ointments with industrial equipment used for processing.
Questions:
1. Define and differentiate between Ointment and creams, lotion and liniment. (98) [4+4]
2. Give different ointment bases with examples. (98)[8]
3. Discuss various methods for manufacturing of ointments. [8]
4. Write a note on different types of raw materials that are used in the manufacture of semisolid
dosage forms. What are the factors that affect skin penetration of drugs from semisolids (96)[16]
5. Preservative in ointment. (95) [4]
6. How do you select the ointment base for a water soluble and insoluble drug to be incorporated for
a medicinal preparation? Discuss on the selection of ointment base (94) [16]
7. Discuss on the importance of packing materials for ointments. What is the influence of packing
materials for ointment storage? (94) [16]
8. Write in brief the factors governing the selection of ointment bases. (93) [6]
9. Give the characteristics and examples of oleaginous bases. (93)[6]
10. Discuss the different methods of ointment preparations. (93) [4]

INTRODUCTION
DEFINITION
 Semi solids are the topical dosage form used for the therapeutic, protective or cosmetic
function. They may be applied to the skin, or used nasally, vaginally, or rectally.
 Pharmaceutical semisolid dosage preparations include ointments, pastes, cream, emulsions,
gels and rigid foams.
Ointments are soft semisolid preparations meant for external application to the skin or mucous
membrane. They usually contain medicament, which is either dissolved or suspended in the base.
They have emollient and protective action.
Creams are semisolid emulsions for external application and are generally of softer consistency and
lighter than ointments. They are less greasy and are easy to apply.
Pastes are semisolid preparations for external application that differs from similar products in
containing a high proportion of finely powdered medicaments. They are stiffer and are usually
employed for their protective action and for their ability to absorb serous discharges from skin lesions.
Thus when protective, rather than therapeutic action is desired, the formulation pharmacists will favor
a paste, but when therapeutic action is required, he will prefer ointments and creams.
Jellies are transparent or translucent, non-greasy, semisolid preparation mainly used externally.
In these systems the liquid phase is entrapped within a three-dimensional polymeric matrix in which a
high degree of physical cross-linking has been introduced.
The polymers (gelling agents) used include:
NATURAL POLYMERS:
 Tragacanth,
 pectin,
 carageenan,
 agar,
 alginic acid
 Gelatin.
SYNTHETIC AND SEMISYNTHETIC POLYMERS:
 Methyl cellulose,
 hydroxymethyl cellulose,
 Carboxymethyl cellulose and Carbopols.

STRUCTURE OF SKIN
The skin has three main layers: the epidermis, dermis and hypodermis.
Epidermis is the outermost layer. It consists of:
(a) The basal layer (innermost) is one cell thick layer. Its cells divide constantly and the daughter
cells are steadily pushed towards the surface.
(b) The prickle cell layer: The cells in this region are linked by tiny bridges or prickles.
(c) The granular layer: When they reach this region, the upwardly moving cells become granules
and begin to synthesize the inert protein keratin.
(d) The horny layer (stratum corneum). This is the outermost layer and the cells are heavily
keratinized and dead. The dead cells sloughs off gradually.
Dermis is the middle and the main part of the skin. The dermis is made up of protein collagen and
elastin. The collagen is in the form of gel that is reinforced by a framework of elastin.
Dermis contains the following structures:
(a) Blood vessels, lymphatics and nerves.
(b) Epidermal appendages e.g. hair follicles, sebaceous glands and sweat glands.
Hypodermis, the innermost layer, consists of adipose tissues. It gives physical protection and thermal
insulation to underlying structures.
 Epidermis is non-granular but is penetrated by hair follicles, sebaceous glands and sweat glands.
 Sebum is the secretion of sebaceous glands. Sebum is a mixture of fatty substances and
emulsifiers; it mixes with water producing a fluid of pH 5.5 that covers the skin surface
and permeates the upper layer of keratinized cells – this is called the “acid-mantle” of skin.
 Keratin is hydrophillic, the stratum corneum normally contains about 20% w/w of water,
the amount varying with atmospheric humidity. This moisture keeps the skin supple and
if its level falls below about 12% the cells becomes dry and brittle and then shrink and
curl at the edges, making the skin feel rough.
 Cracking may follow, causing discomfort. Loss of water may be the result of excessive
evaporation, over-usage of detergents (which removes sebum) and cold weather (which
inhibits sebum production).
PERMEABILITY OF DRUG THROUGH EPIDERMIS

Most dermatological preparations belong to one of two classes:
1. Preparation intended to remain on the surface
E.g. products for penetration or for emollient action.

2. Preparations intended to penetrate the skin but will not enter into blood stream
Drugs penetrate the epidermis by two man routes:
(a) Through the keratinized cells of the stratum corneum.
The keratinized cells are fused together so drug molecules directly diffuse through them. These
cells contains keratin which is hydrophilic and phospholipids which is hydrophobic, so drug
molecules having solubility in both water and oil have good permeability through this route.
(b) Via hair follicles
Although the hair follicles occupy only a small area of the total epidermis, they provide a very
important route of penetration. The fat soluble drugs dissolve in sebum, diffuses in to the sebum-
filled follicles and passes to dermis.
FACTOR AFFECTING PERMEABILITY OF A DRUG THROUGH SKIN

A. Factor associated with the skin
(a) Hydration of the horny layer
The hydration of keratinized cells is raised by covering the area with a moisture-proof plastic film
to prevent evaporation of perspiration. Hydration increases the drug penetration.
(b) Thickness of the horny layer
The horny layer is thickest on palms and soles and thinnest on the face; penetration rate increases
with decreased thickness of horny layer.
(c) Skin condition
The permeability of the skin is affected by age, disease, climate and injury. For example,
absorption occurs rapidly in children and if the dermis is exposed by a wound or burn.
B. Factors associated with the medicament
(a) Solubility of the drug
Highly lipid soluble molecules enters through hair follicles. Moderately lipid soluble molecules
penetrates directly across the horny layer.
(b) Dissociation constant (pKa)
If a drug is ionized in the surrounding pH of the dermis then the penetration of the ionic species
are restricted by electrostatic interactions. Degree of ionization depends on the pKa of the drug.
E.g. Methyl salicylate and methyl nicotinate penetrate much faster than salicylic acid and nicotinic
acid respectively.
(c) Particle size
Reducing the particle size increases the dissolution of a poorly soluble drug in suspension and thus
increases the release rate from the vehicle.

(d) Crystal structure

The metastable polymorph is much more soluble than its stable form, so the release of drug in
metastable state is much faster than stable form.
C. Factors associated with vehicles
The rate of release of a drug from a vehicle to stratum corneum is governed by vehicle-to-stratum
corneum partition coefficient. The thermodynamic activity of the drug in the vehicle is the product of
the concentration of the drug and the activity coefficient () of the drug in the vehicle. Drugs held
firmly by the vehicle exhibit low activity coefficient, hence slow rate of release from that drug-vehicle
combination. Drug held loosely by the vehicle shows higher activity coefficient, hence shows faster
rate of release.
The vehicles may enhance the penetration of a drug in one or more of the following ways:-
a) By ensuring good contact with the surface of the body
b) By increasing the degree of hydration of the stratum corneum
c) By penetrating the epidermis
d) By directly altering the permeability of the skin
(a) Contact with body surface

Sticky bases such as soft paraffin, Paraffin ointment B.P.C., Simple ointment B.P. etc. adheres well
to the skin but are difficult to apply evenly and remove completely.
Creams are easier to apply and remove. Oil in water (o/w) creams mix with sebum and are more
suitable for weeping or wounded surface.
(b) Hydration of stratum corneum

An occlusive layer reduces evaporation of water from skin, increasing hydration of the horny layer
and, therefore, promotes penetration of medicament.
E.g. hydrocarbons, wool fat and isopropyl myristate containing ointments produce occlusive films
on the skin. Water in oil (o/w) type creams have some occlusive effects.
Humectants like glycerols are not good for retaining water because at low atmospheric humidities,
because they tend to increase loss of water by absorbing it from the skin.
(c) Penetration of the epidermis
Bases miscible with the sebum penetrate into the regions of the skin in which sebum is found.
E.g. Woolfat (originating from sebaceous glands of sheep) penetrates into the skin.
Vegetable oils penetrate more slowly and liquid paraffin does not penetrate at all.

(d) Alteration of skin permeability

Penetration can be improved by dissolving the medicament in an organic liquid such as ethanol,
dimethylformamide (DMF), dimethyl acetamide, dimethylsulfoxide (DMSO) and propylene glycol.
They increases the hydration of skin.
OINTMENT
Definition: Ointments are semisolid preparations for application to the skin or mucosae. The ointment
bases are almost always anhydrous and generally contains one or more medicaments in suspension or
solution.
Characteristics of an ideal ointment:
1. It should be chemically and physically stable.
2. It should be smooth and free from grittiness.
3. It should melt or soften at body temperature and be easily applied.
4. The base should be non-irritant and should have no therapeutic action.
5. The medicament should be finely divided and uniformly distributed throughout the base.
Classification of ointments
According to their therapeutic properties based on penetration of skin.
(a) Epidermic,
(b) Endodermic,
(c) Diadermic
(a) Epidermic ointments

 These ointments are intended to produce their action on the surface of the skin and produce
local effect.
 They are not absorbed.
 They acts as protectives, antiseptics and parasiticides.
(b) Endodermic ointments
 These ointments are intended to release the medicaments that penetrate into the skin.
 They are partially absorbed and acts as emollients, stimulants and local irritants.
(c) Diadermic ointments
 These ointments are intended to release the medicaments that pass through the skin and
produce systemic effects.

OINTMENT BASES
The ointment base is that substance or part of an ointment preparation which serves as carrier or
vehicle for the medicament.
An ideal ointment base should be inert, stable, smooth, compatible with the skin, non-irritating and
should release the incorporated medicaments readily.
Classification of ointment bases:
1. Oleaginous bases
2. Absorption bases
3. Water-miscible bases
4. Water soluble bases
OLEAGINOUS BASES
These bases consists of oils and fats. The most important are the
Hydrocarbons i.e. petrolatum, paraffins and mineral oils.
The animal fat includes lard.
The combination of these materials can produce a product of desired melting point and viscosity.
(a) Petrolatum (Soft paraffin)
 This is a purified mixture of semi-solid hydrocarbons obtained from petroleum or heavy
lubricating oil.
Yellow soft paraffin (Petrolatum; Petroleum jelly)
 This a purified mixture of semisolid hydrocarbons obtained from petroleum. It may contain
suitable stabilizers like, antioxidants e.g. -tocopherol (Vitamin E), butylated hydroxy toluene
(BHT) etc.
 Melting range: 38 to 560C.
White soft paraffin (White petroleum jelly, White petrolatum)
 This a purified mixture of semisolid hydrocarbons obtained from petroleum, and wholly or
partially decolorized by percolating the yellow soft paraffin through freshly burned bone black
or adsorptive clays.
 Melting Range: 38 to 560C.
 Use: The white form is used when the medicament is colourless, white or a pastel shade.
 This base is used in
Dithranol ointment B.P.
Ammoniated Mercury and Coal tar ointment B.P.C. Zinc ointment B.P.C.

(b) Hard paraffin (Paraffin)

This is a mixture of solid hydrocarbons obtained from petroleum.
It is colourless or white, odorless, translucent, wax-like substance. It solidifies between 50 and 570 C
and is used to stiffen ointment bases.
(c) Liquid paraffin (Liquid petrolatum, White mineral oil)
It is a mixture of liquid, hydrocarbons obtained from petroleum. It is transparent, colourless,
odourless, viscous liquid.
On long storage it may oxidize to produce peroxides and therefore, it may contain tocopherol or BHT
as antioxidants.
It is used along with hard paraffin and soft paraffin to get a desired consistency of the ointment. Tubes
for eye, rectal and nasal ointments have nozzles with narrow orifices through which it is difficult to
expel very viscous ointments without the risk of bursting the tube. To facilitate the extrusion upto 25%
of the base may be replaced by liquid paraffins.
Advantages of hydrocarbons bases:
(i) They are not absorbed by the skin. They remain on the surface as an occlusive layer that restricts
the loss of moisture hence, keeps the skin soft.
(ii) They are sticky hence ensures prolonged contact between skin and medicament.
(iii)They are almost inert. They consist largely of saturated hydrocarbons, therefore, very few
incompatibilities and little tendency of rancidity are there.
(iv) They can withstand heat sterilization, hence, sterile ophthalmic ointments can be prepared with it.
(v) They are readily available and cheap.
Disadvantages of hydrocarbon bases;
(i) It may lead to water logging followed by maceration of the skin if applied for a prolonged period.
(ii) It retains body heat, which may produce an uncomfortable feeling of warmth.
(iii)They are immiscible with water; as a result rubbing onto the surface and removal after treatment
both are difficult.
(iv) They are sticky, hence makes application unpleasant and leads to contamination of clothes.
(v) Water absorption capacity is very low, hence, these bases are poor in absorbing exudate from
moist lesions.

ABSORPTION BASE
 The term absorption base is used to denote the water absorbing or emulsifying property of
these bases and not to describe their action on the skin.
 These bases (some times called emulsifiable ointment bases) are generally anhydrous
substances which have the property of absorbing (emulsifying) considerable quantity of water
yet retaining its ointment-like consistency.
 Preparations of this type do not contain water as a component of their basic formula but if
water is incorporated a W/O emulsion results.
Wool Fat (anhydrous lanolin)
It is the purified anhydrous fat like substance obtained from the wool of sheep.
 It is practically insoluble in water but can absorb water upto 50% of its own weight. Therefore it is
used in ointments the proportion of water or aqueous liquids to be incorporated in hydrocarbon
base is too large.
 Due to its sticky nature it is not used alone but is used along with other bases in the preparation of
a number of ointments.
E.g. Simple ointment B.P. contains 5% and the B.P. eye ointment base contains 10% Woolfat.
Hydrous Wool Fat (Lanolin)
 It is a mixture of 70 % w/w wool fat and 30 % w/w purified water. It is a w/o emulsion. Aqueous
liquids can be emulsified with it.
 It is used alone as an emollient.
 Example: - Hydrous Wool Fat Ointment B.P.C., Calamine Coal Tar Ointment.
Wool Alcohol
It is the emulsifying fraction of wool fat. Wool alcohol is obtained from wool fat by treating it with
alkali and separating the fraction containing cholesterol and other alcohols. It contains not less than
30% of cholesterol.
Use:-
 It is used as an emulsifying agent for the preparation of w/o emulsions and is used to absorb water
in ointment bases.
 It is also used to improve the texture, stability and emollient properties of o/w emulsions.
Examples: - Wool alcohol ointment B.P. contains 6% wool alcohol and hard, liquid and soft paraffin.
Beeswax
It is purified wax, obtained from honey comb of bees.
It contains small amount of cholesterol. It is of two types: (a) yellow beeswax and (b) white beeswax.

Use:-
Beeswax is used as a stiffening agent in ointment preparations.
Examples:-Paraffin ointment B.P.C. contains beeswax.
Cholesterol
It is widely distributed in animal organisms. Wool fat is also used as a source of cholesterol.
Use: - It is used to increase the water absorbing power of an ointment base.
Example: - Hydrophilic petroleum U.S.P. contains:
Cholesterol 3%
Stearyl alcohol 3%
White beeswax 8%
White soft paraffin 86%
Advantages of absorption bases:

(i) They are less occlusive nevertheless, are good emollient.
(ii) They assist oil soluble medicaments to penetrate the skin.
(iii)They are easier to spread.
(iv) They are compatible with majority of the medicaments.
(v) They are relatively heat stable.
(vi) The base may be used in their anhydrous form or in emulsified form.
(vii)They can absorb a large quantity of water or aqueous substances.
Disadvantages: Inspite of their hydrophilic nature, absorption bases are difficult to wash.
WATER MISCIBLE BASES

 They are miscible with an excess of water. Ointments made from water-miscible bases are
easily removed after use.
 There are three official anhydrous water-miscible ointment bases:-
Example:-
 Emulsifying ointment B.P.  Contains anionic emulsifier.
 Cetrimide emulsifying ointment B.P.  contains cationic emulsifier
 Cetomacrogol emulsifying ointment B.P.  contains non-ionic emulsifier
Uses: they are used to prepare o/w creams and are easily removable ointment bases
E.g. Compound Benzoic Acid Ointment (Whitfield’s Ointment)  used as antifungal ointment.

Advantages of water miscible bases:

(i) Readily miscible with the exudates from lesions.
(ii) Reduced interference with normal skin function.
(iii)Good contact with the skin, because of their surfactant content.
(iv) High cosmetic acceptability, hence there is less likelihood of the patients discontinuing treatment.
(v) Easy removal from the hair.
WATER SOLUBLE BASES

Water soluble bases contain only the water soluble ingredients and not the fats or other greasy
substances, hence, they are known as grease-less bases.
Water soluble bases consists of water soluble ingredients such as polyethylene glycol polymers (PEG)
which are popularly known as “carbowaxes” and commercially known as “macrogols”.
They are a range of compounds with the general formula:
CH2OH. (CH2OCH2) n CH2OH
The PEGs are mixtures of polycondensation products of ethylene and water and they are described by
numbers representing their average molecular weights. Like the paraffin hydrocarbons they vary in
consistency from viscous liquids to waxy solids.
Example:-
Macrogols 200, 300, 400  viscous liquids
Macrogols 1500  greasy semi-solids
Macrogols 1540, 3000, 4000, 6000  waxy solids.
Different PEGs are mixed to get an ointment of desired consistency.

Advantages of PEGs as ointment base:
(a) They are water soluble; hence, very easily can be removed from the skin and readily miscible with
tissue exudates.
(b) Helps in good absorption by the skin.
(c) Good solvent properties. Some water-soluble dermatological drugs, such as salicylic acid,
sulfonamides, sulfur etc. are soluble in this bases.
(d) Non-greasy.
(e) They do not hydrolyze, rancidity or support microbial growth.
(f) Compatibility with many dermatological medicaments.

Disadvantages:
(a) Limited uptake of water. Macrogols dissolve when the proportion of water reaches about 5%.
(b) Reduction in activity of certain antibacterial agents, e.g. phenols, hydroxybenzoates and
quaternary compounds.
(c) Solvent action on polyethylene and Bakelite containers and closures.
Certain other substances which are used as water soluble ointment bases include tragacanth, gelatin,
pectin, silica gel, sodium alginate, cellulose derivatives, etc.
FACTORS GOVERNING SELECTION OF AN IDEAL OINTMENT BASE

1. Dermatological factors
2. Pharmaceutical factors
1. Dermatological factors
(a) Absorption and Penetration:
‘Penetration’ means passage of the drug across the skin i.e. cutaneous penetration, and ‘absorption’
means passage of the drug into blood stream.
 Medicaments which are both soluble in oil and water are most readily absorbed though the skin.
 Whereas animal and vegetable fats and oils normally penetrate the skin.
 Animals fats, e.g. lard and wool fat when combined with water, penetrates the skin.
 O/w emulsion bases release the medicament more readily than greasy bases or w/o emulsion bases.
(b) Effect on the skin
 Greasy bases interfere with normal skin functions i.e. heat radiation and sweating.
 They are irritant to the skin.
 O/w emulsion bases and other water miscible bases produce a cooling effect due to the evaporation
of water.
(c) Miscibility with skin secretion and sebum
Skin secretions are more readily miscible with emulsion bases than with greasy bases.
Due to this the drug is more rapidly and completely released to the skin.
(d) Compatibility with skin secretions:
The bases used should be compatible with skin secretions and should have pH about 5.5 because
the average skin pH is around 5.5. Generally neutral ointment bases are preferred.

(e) Non-irritant
All bases should be highly pure and bases especially for eye ointments should be non-irritant and
free from foreign particle.
(f) Emollient properties
Dryness and brittleness of the skin causes discomfort to the skin therefore, the bases should keep
the skin moist. For this purpose water and humectants such as glycerin, propylene glycol are used.
Ointments should prevent rapid loss of moisture from the skin.
(g) Ease of application and removal
The ointment bases should be easily applicable as well as easily removable from the skin by simple
washing with water. Stiff and sticky ointment bases require much force to spread on the skin and
during rubbing newly formed tissues on the skin may be damaged.
2. PHARMACEUTICAL FACTORS
(a) Stability
Fats and oils obtained from animal and plant sources are prone to oxidation unless they are suitably
preserved. Due to oxidation odour comes out. This type of reactions are called rancidification.
Lard, from animal origin, rancidify rapidly. Soft paraffin, simple ointment and paraffin ointment are
inert and stable. Liquid paraffin is also stable but after prolonged storage it gets oxidized.
Therefore, an antioxidant like tocopherol (Vit -E) may be incorporated. Other antioxidants those
may be used are butylated hydroxy toluene (BHT) or butylated hydroxy anisole (BHA).
(b) Solvent properties
Most of the medicaments used in the preparation of ointments are insoluble in the ointment bases
therefore, they are finely powdered and are distributed uniformly throughout the base.
(c) Emulsifying properties
Hydrocarbon bases absorbs very small amount of water.
Wool fat can take about 50% of water and when mixed with other fats can take up several times its
own weight of aqueous solution.
Emulsifying ointment, cetrimide emulsifying ointment and cetomacrogol emulsifying ointment are
capable of absorbing considerable amount of water, forming w/o creams.
(d) Consistency
The ointments produced should be of suitable consistency. They should neither be hard nor too soft.
They should withstand climatic conditions. Thus in summer they should not become too soft and in
winter not too hard to be difficult to remove from the container and spread on the skin.
The consistency of an ointment base can be controlled by varying the ratio of hard and liquid
paraffin.

PREPARATION OF OINTMENTS
A well-made ointment is 
(a) Uniform throughout i.e. it contains no lumps of separated high melting point ingredients of the
base, there is no tendency for liquid constituents to separate and insoluble powders are evenly
dispersed.
(b) Free from grittiness, i.e. insoluble powders are finely subdivided and large lumps of particles are
absent. Methods of preparation must satisfy this criteria.
Two mixing techniques are frequently used in making ointments:
1. Fusion, in which ingredients are melted together and stirred to ensure homogeneity.
2. Trituration, in which finely-subdivided insoluble medicaments are evenly distributed by grinding
with a small amount of the base or one of its ingredients followed by dilution with gradually
increasing amounts of the base.
1. OINTMENTS PREPARED BY FUSION METHOD:
When an ointment base contain a number of solid ingredients such as white beeswax, cetyl alcohol,
stearyl alcohol, stearic acid, hard paraffin, etc. as components of the base, it is required to melt them.
The melting can be done in two methods:
Method-I
The components are melted in the decreasing order of their melting point i.e. the higher m.p. substance
should be melted first, the substances with next melting point and so on. The medicament is added
slowly in the melted ingredients and stirred thoroughly until the mass cools down and homogeneous
product is formed.
Advantages:
This will avoid over-heating of substances having low melting point.
Method-II
All the components are taken in subdivided state and melted together.
Advantages:
The maximum temperature reached is lower than Method-I, and less time was taken possibly due to
the solvent action of the lower melting point substances on the rest of the ingredients.
Cautions:
(i) Melting time is shortened by grating waxy components (i.e. beeswax, wool alcohols, hard-paraffin,
higher fatty alcohols and emulsifying waxes) by stirring during melting and by lowering the dish
as far as possible into the water bath so that the maximum surface area is heated.

(ii) The surface of some ingredients discolors due to oxidation e.g. wool fats and wool alcohols and
this discolored layers should be removed before use.
(iii)After melting, the ingredients should be stirred until the ointment is cool, taking care not to cause
localized cooling, e.g. by using a cold spatula or stirrer, placing the dish on a cold surface (e.g. a
plastic bench top) or transferring to a cold container before the ointment has fully set. If these
precautions are ignored, hard lumps may separate.
(iv) Vigorous-stirring, after the ointment has begun to thicken, causes excessive aeration and should be
avoided.
(v) Because of their greasy nature, many constituents of ointment bases pickup dirt during storage,
which can be seen after melting. This is removed from the melt by allowing it to sediment and
decanting the supernatant, or by passage through muslin supported by a warm strainer. In both
instances the clarified liquid is collected in another hot basin.
(vi) If the product is granular after cooling, due to separation of high m.p. constituents, it should be
remelted, using the minimum of heat, and again stirred and cooled.
Example:
(i) Simple ointment B.P. contains
Wool fat 50g
Hard paraffin 50g
Cetostearyl alcohol 50g
White soft paraffin 850g
Type of preparation: Absorption ointment base

Procedure:
Hard paraffin and cetostearyl alcohol on water-bath. Wool fat and white soft paraffin are mixed and
stirred until all the ingredients are melted. If required decanted or strained and stirred until cold and
packed in suitable container.
(ii) Paraffin ointment base
Type of preparation: Hydrocarbon ointment base
(iii) Wool alcohols ointment B.P.
Type of preparation: Absorption base
(iv) Emulsifying ointment B.P.
Type of preparation: Water-miscible ointment base.

(v) Macrogol ointment B.P.C

Type of preparation: Water soluble ointment base
Formula: Macrogol 4000
Liquid Macrogol 300
Method:
 Macrogol 4000 is melted and previously warmed liquid macrogol 300 is added.
 Stirred until cool.
2. OINTMENT PREPARED BY TRITURATION

This method is applicable in the base or a liquid present in small amount.
(i) Solids are finely powdered are passed through a sieve (# 250, # 180, #125).
(ii) The powder is taken on an ointment-slab and triturated with a small amount of the base. A steel
spatula with long, broad blade is used. To this additional quantities of the base are incorporated
and triturated until the medicament is mixed with the base.
(iii)Finally liquid ingredients are incorporated. To avoid loss from splashing, a small volume of liquid
is poured into a depression in the ointment a thoroughly incorporated before more is added in the
same way. Splashing is more easily controlled in a mortar than on a tile.
Example:
(i) Whitfield ointment (Compound benzoic acid ointment B.P.C.)
Formula: Benzoic acid, in fine powder 6gm
Salicylic acid, in fine powder 3gm
Emulsifying ointment 91gm
Method: Benzoic acid and salicylic acid are sieved through No. 180 sieves. They are mixed on the tile
with small amount of base and levigated until smooth and dilute gradually.
(ii) Salicylic acid sulphur ointment B.P.C.
3. OINTMENT PREPARATION BY CHEMICAL REACTION

Chemical reactions were involved in the preparation of several famous ointments of the past, e.g.
Strong Mercuric Nitrate Ointment, of the 1959 B.P.C.
(a) Ointment containing free iodine
Iodine is only slightly soluble in most fats and oils but readily soluble.
Iodine is readily soluble in concentrated solution of potassium iodide due to the formation of
molecular complexes KI.I2, KI.2I2, KI.3I2 etc.
These solutions may be incorporated in absorption-type ointment bases.

E.g. Strong Iodine Ointment B.Vet.C (British Veterinary Pharmacopoeia) is used to treat ringworm in
cattle. It contains free iodine. At one time this type of ointments were used as counter-irritants in
the treatment of human rheumatic diseases but they were not popular because:
They stain the skin a deep red color.
(i) Due to improper storage the water dries up and the iodine crystals irritate the skin, hence glycerol
was some times added to dissolve the iodine-potassium iodide complex instead of water.
 Example:
o Strong Iodine Ointment B. Vitamin C.
 Iodine
 Woolfat
 Yellow soft paraffin
 Potassium iodide
 Water
Procedure:
(i) KI is dissolved in water. I2 is dissolved in it.
(ii) Woolfat and yellow soft paraffin are melted together over water bath. Melted mass is cooled to
about 400C.
(iii)I2 solution is added to the melted mass in small quantities at a time with continuos stirring until a
uniform mass is obtained.
(iv) It is cooled to room temperature and packed.
Use: - Ringworm in cattle.
(b) Ointment containing combined iodine

Fixed oils and many vegetable and animal fats absorb iodine which combines with the double bonds of
the unsaturated constituents, e.g.
CH3. (CH2) 2. CH = CH. (CH2) 7. COOH + I2  CH3. (CH2) 2. CHI.CHI. (CH2) 7. COOH
Oleic acid di-iodostearic acid
Example: Non-staining Iodine Ointment B.P.C. 1968

Iodine
Arachis Oil
Yellow Soft Paraffin

Method:
(a) Iodine is finely powdered in a glass mortar and required amount is added to the oil in a glass-
stoppered conical flask and stirred well.
(b) The oil is heated at 500C in a water-bath and stirred continually. Heating is continued until the
brown color is changed to greenish-black; this may take several hours.
(c) From 0.1g of the preparation the amount of iodine is determined by B.P.C. method and the amount
of soft paraffin base is calculated to give the product the required strength.
(d) Soft paraffin is warmed to 400C. The iodized oil is added and mixed well. No more heat is applied
because this causes deposition of a resinous substance.
(e) The preparation is packed in a warm, wide-mouthed, amber color, glass bottle. It is allowed to cool
without further stirring.
4. PREPARATION OF OINTMENTS BY EMULSIFICATION
An emulsion system contain an oil phase, an aqueous phase and an emulsifying agent.
For o/w emulsion systems the following emulsifying agents are used:
(i) Water soluble soap
(ii) cetyl alcohol
(iii) Glyceryl monostearate
(iv) Combination of emulsifiers: triethanolamine stearate + cetyl alcohol
(v) Non-ionic emulsifiers: glyceryl monostearate, glyceryl monooelate, propylene glycol stearate
For w/o emulsion creams the following emulsifiers are used:
(i) Polyvalent ions e.g magnesium, calcium and aluminium are used.
(ii) Combination of emulsifiers: beeswax + divalent calcium ion
 The viscosity of this type of creams prevent coalescence of the emulsified phases and helps in
stabilizing the emulsion.
Example:
COLD CREAM:
Procedure:
(i) Water immiscible components e.g. oils, fats, waxes are melted together over water bath (700C).
(ii) Aqueous solution of all heat stable, water soluble components are heated (700C).
(iii)Aqueous solution is slowly added to the melted bases with continuous stirring until the product
cools down and a semi-solid mass is obtained.
N.B. The aqueous phase is heated otherwise high melting point fats and waxes will immediately
solidify on addition of cold aqueous solution.

MANUFACTURE OF OINTMENTS / CREAMS IN INDUSTRIAL SCALE

1. Preparation of oil and aqueous phase
Oils + Fats Water soluble ingredients + Purified water
 Equipment: Steam jacketed kettle  Equipment: Mechanical stirrer
Melted and mixed Dissolved
 
Strained through several layers of cheese Filtered
Cloths to remove foreign matter 
Heated to the melting point of oil phase
 Cakes, flakes or powdered waxes are directly weighed in a physical balance.

 Semisolid petrolatum is melted in the container supplied by an immersion heater, the liquid
petrolatum is then transferred by a metering pump through metal reinforced inert plastic hoses and
insulated pipes.
2. Mixing of oil and water phases

Mixing temperature is 70–720C for proper mixing.
Three methods of mixing are there:
(A) Simultaneous blending (B) Addition of disperse phase (C) Addition of continuous
to continuous phase phase to disperse phase
Continuous
Dispersed phase
Oil Water Dispersed
phase Continuous
phase phase
 For continuous or large

batch operation  For an emulsion having low  For an emulsion formed by
 Equipments volume of dispersed phase. phase inversion method.
Proportioning pump  Equipment:  Equipment:
Continuous mixer Simple metering pump Simple metering pump.
 Batch sizes are on weight basis. For weighing a hydraulic load cell is fitted under one of the leg of
the mixing kettle.

3. Cooling the semisolid

 Cooling should be slow to prevent crystallization of high m.p. waxes.
 Perfumes are added at 43 to 450C.
 Equipments: Kettle fitted with heating / cooling arrangements, agitator and sweep blades
(For scrapping the wall).
Cooled to 43 to 450C
 Kettle with agitator and sweep blades
Addition of perfume

Addition of drug powder

Dispersed or dissolved
4. Homogenization
Creams or ointments
 Equipment: Low-shear gear pump and
Roller mill / colloid mill / valve type homogenizer
Homogenization
5. Storage of semisolids
Stored before packaging. In the mean time Q.C. report comes. Stored in a tight-fitting stainless
steel (SS#316) container.
6. Transfer of materials for packaging

Equipment: Ointment filling machine
Washing of the equipments with high-pressure (up to 1000psi), low-volume pumps and hot water and
detergents should be done.
To sterilize the equipments, containers, pumps and other accessories are flushed with chlorinated
water or formalin – followed by rinsing them with bacteria free water.

STABILITY OF OINTMENTS
The ointments should remain stable from the time of preparation to the time when the whole of it is
consumed by the user.
(i) To stop microbial growth preservatives are added. Preservatives for ointment includes: p-hydroxy
benzoates, phenol, benzoic acid, sorbic acid, methyl paraben, propyl paraben, quaternary
ammonium compounds, mercury compounds etc.
(ii) The preservatives should not react with any of the component of the formulation. Plastic
containers may absorb the preservative and thereby decreasing the concentration of preservative
available for killing the bacteria.
(iii)Some ingredients like wool fat and wool alcohols are susceptible to oxidation. Therefore, a
suitable antioxidant may be incorporated to protect the active ingredients from oxidation.
(iv) Incompatible drugs, emulsifying agents and preservatives must be avoided. The drugs which are
likely to hydrolyze must be dispensed in an anhydrous base.
(v) Humectants such as, glycerin, propylene glycol and sorbitol may be added to prevent the loss of
moisture from the preparation.
(vi) Ointment must be stored at an optimum temperature otherwise separation of phases may take place
in the emulsified products which may be very difficult to remix to get a uniform product.
PRESERVATIVE:
PRESERVATIVE some base, although, resist microbial attack but because of their high water content,
it require an antimicrobial preservative.
Commonly used preservatives include
 Methyl hydroxybenzoate
 Propyl hydroxybenzoate Chlorocresol
 Benzoic acid Phenyl mercuric nitrate
ANTIOXIDANTS:
ANTIOXIDANTS Oxygen is a highly reactive atom that is capable of becoming part of potentially
damaging molecules commonly called “free radicals.” Free radicals are capable of attacking the
healthy cells of the body, causing them to lose their structure and function. To prevent this an
antioxidants are added.
E.g. Butylated hydroxy anisole, Butylated hydroxy toluene.

CLASSIFICATION OF ANTIOXIDANTS:
CLASSIFICATION OF ANTIOXIDANTS ANTIOXIGENS REDUCING AGENT ANTIOXIDANT
SYNERGISTS Acts by reacting with free radical.
E.g. butylated hydroxyanisole (BHA)
Butylated hydroxytoluene (BHT)
Tocopherlos (used for oil system)
Have lower redox potential than drug, hence gets oxidised first.
E.g. Ascorbic acid Potassium and sodium metabisulfite Thiosulfite (used for aqueous system)
Chelating or sequestering agent, enhacne the effects of antioxidants.
E.g. Citric acid Tartaric acid lecithin 26
GELLING AGENTS:
GELLING AGENTS gelling agents, forms a gel, dissolving in the liquid phase as a colloid mixture
that forms a weakly cohesive internal structure. These are organic hydrocolloids or hydrophilic
inorganic substances.
E.g. Tragacanth, Sodium Alginate, Pectin, Starch, Gelatin, Cellulose Derivatives, Carbomer, and
Poly Vinyl Alcohol Clays.
PERMEATION ENHANCERS:
Skin can act as a barrier. With the introduction of various penetration enhancers, penetration of the
drug through the skin can be improved. Sr. no Permeation enhancer Drugs used
1. Menthol, carvacrol, linalool Propranolol hydrochloride
2. Limonene Indomethacin, ketoprofen
3. Geraniol, nerolidol Diclofenac sodium
4. Oleic acid Piroxicam
EMULSIFIER:
EMULSIFIER An emulsifier (emulgent) is a substance that stabilizes an emulsion by increasing its
kinetic stability. One class of emulsifiers is known as surface active substances, or surfactants. Ideal
properties of emulsifier includes,
a) Must reduce surface tension for proper emulsification.
b) Prevents coalescence and should quickly absorb around the dispersed phase.
c) Ability to increase the viscosity at low concentration.
d) Effective at low concentration

SIZE REDUCTION AND SIZE SEPARATION PHARMAROCKS: THE WAY OF SUCCESS
PHARMAROCKS: AMAR RAVAL

SIZE REDUCTION AND SIZE SEPARATION
Syllabus:
Definition, objectives of size reduction and size separation, factors affecting size reduction, laws governing energy and
power requirements of mills including ball mill, hammer mill, fluid energy mill etc., sieve analysis, standards of sieves,
size separation equipment shaking and vibrating screens, gyratory screens, cyclone separator, air separator, bag filters,
cottrell precipitator, scrubbers, size separators basing on sedimentation theory.
Definition
Size reduction (or Comminution)

Size reduction or comminution is the process of reducing substances to smaller particles.
Size separation (or Classification)

Size separation (or classification) is a process in which particles of desired size are separated from other fractions.
Objectives
Objectives of size reduction
1. Size reduction leads to increase of surface area.
Example-I: The rate of dissolution of solid drug particles increases many folds after size reduction. Griseofulvin, an
antifungal drug, when administered in its micronized form shows around five times better absorption.
Example-II: The absorptive power of charcoal and kaolin increases after size reduction due to increase in surface
area.
2. Size reduction produces particles in narrow size range. Mixing of powders with narrow size range is easier.
3. Pharmaceutical suspensions require finer particle size. It reduces rate of sedimentation.
4. Pharmaceutical capsules, insufflations (i.e. powders inhaled directly into the lungs), suppositories and ointments
require particles size to be below 60m size.
Objectives of size separation

1. Any solid materials, after size reduction, never gives particles of the same size but contains particles of varying
sizes. The size-reduced particles are then passed through sieves to get fractions of narrow size range.
2. During tablet granulation the granules should be within narrow size range, otherwise, weight variation will take
place during tablet punching.
Factors affecting size-reduction
The pharmaceutical industry uses a great variety of materials, including chemical substances, animal tissues and
vegetable drugs.
A. Factors related to the nature of raw materials

Hard materials: Hard materials like pumice and iodine are most difficult to comminute. During size reduction these
types of materials will produce abrasive wear of milling surfaces, which will then contaminate the material.
Fibrous materials: Crude drugs obtained from plants like glycyrrhiza, rauwolfia, ginger etc. are fibrous in nature and
cannot be crushed by pressure. So they may be size-reduced by cutter mill.
Friable materials: Sucrose and dried filter cakes are friable (i.e. brittle) hence they are easy to comminute by hammer
mill or fluid energy mill.
Plastic materials: Synthetic gums, waxes and resins become soft and plastic during milling. These low melting
substances should be chilled (made cold) before milling. These types of materials are milled by using hammer mill and
fluid energy mill.
Hygroscopic materials: Hygroscopic materials absorbs moisture rapidly hence they must be comminuted inside a
closed equipment like ball-mill.
Thermolabile materials: Thermolabile materials like vitamins and antibiotics are milled inside chilled equipment.
Inflammable materials: Fine dust, such as dextrin, starch and sulphur, is a potential explosive mixture under certain
conditions. All electrical switches should be explosive proof and the mill should be earthed properly.
Particle size of the feed: For a mill to operate satisfactorily, the feed should be of proper size.
Moisture content: Presence of more than 5% moisture hinders the milling process and produces a sticky mass.
AMAR RAVAL EMAIL ID Pharmarocks77@gmail.com HELPLINE (+91) 9016312020 1|Pa g e

B. Factors related to the nature of the finished product

Particle size: Moderately coarse powders may be obtained from various impact mill. If very fine particles like
micronized particles of griseofulvin may be obtained from fluid energy mill.
Ease of sterilization: When preparations are intended for parenteral (injection) purpose and ophthalmic uses, size
reduction must be conducted in a sterile environment. Mills should be sterilized by steam before use.
Contamination of milled materials: In case of potent drugs and low dose products, contamination of the products
should be avoided. Equipment free from wearing (e.g. fluid energy mill) may be used in this case.
Laws governing energy and power requirements of mills

During size reduction energy is supplied to the equipment (mill). Very small amount of energy (less than 2%) actually
produce size reduction. Rest of the energy is dissipated (wasted) in:
(i) Elastic deformation of particles
(ii) Transport of material within the milling chamber
(iii) Friction between the particles
(iv) Friction between the particles and mill
(v) Generation of heat
(vi) Vibration and noise.
(vii) Inefficiency of transmission and motor.
Theories of milling
A number of theories have been proposed to establish a relationship between energy input and the degree of size
reduction produced.
Rittinger’s theory
Rittinger’s theory suggests that energy required in a size reduction process is proportional to the new surface area
produced.
E  K R (Sn - S i )
where, E = energy required for size reduction
KR = Rittinger’s constant
Si = initial specific surface area
Sn = final specific surface area
Application: It is most applicable in size reducing brittle materials undergoing fine milling.
Bond’s theory
Bond’s theory states that the energy used in crack propagation is proportional to the new crack length produced
 1 1 
E  2K B  - 
 d di 
 n 
KB = Bond’s work index
di = initial diameter of particles
dn = final diameter of particles
Application: This law is useful in rough mill sizing. The work index is useful in comparing the efficiency of milling
operations.
Kick’s theory
Kick’s theory states that the energy used in deforming (or fracturing) a set of particles of equivalent shape is
proportional to the ratio of change of size, or:
di
E  K K log
dn
KK = Kick’s constant
di = initial diameter of particles
dn = final diameter of particles
Application: For crushing of large particles Kick’s theory most useful.

Walker’s theory
Walker proposed a generalized differential form of the energy-size relationship:
dD
dE  - K
Dn
where E = amount of energy (work done) required to produce a change
D = size of unit mass
K = Constant
n = constant
For n =1.0 Walker equation becomes Kick’s theory used for coarse particles > 1 m.
For n =1.5 Walker equation becomes Bond’s theory. This theory is used when neither Kick’s nor Rittinger’s law is
applicable.
For n =2.0 Walker equation becomes Rittinger’s theory used for fine particles < 1 m size.
Methods of size reduction
Method Diagram Common Examples
Scissors
Cutting Cutter mill
Roller mill
Compression Crusher mill
Approximate
increase in
fineness of Hammer mill
product
Impact
Attirtion File
(Pressure and Fluid energy mill
friction)
Table: Uses of size reduction methods
Degree of size reduction Typical methods Examples

Large pieces Cutter or compression mills Rhubarb
Coarse powders Impact mills Liquorice, cascara
Fine powders Combined impact and attrition mills Rhubarb , belladonna
Very fine powders Fluid energy mills Vitamins and antibiotics

CUTTER MILL
Method of size reduction: Cutting
Construction and working principle:

The equipment has two parts – one is rotor and another part is the
casing. Stationary knives are fitted on the casing and rotating knives
are fitted on the rotor. Feed enters through the top hopper. The rotor
rotates and both stationary and rotating knives cut the material into
pieces. The lower part consists of a screen, so that material is
retained in the mill until sufficient degree of size reduction has been
effected.
Applications:
This method is used to obtain coarse degree of size reduction of soft
materials. Applied in size reduction of roots, peels or woods, prior
to extraction.
ROLLER MILL
Method of size reduction: Compression

The roller mill has two cylindrical rolls of stone or metal, mounted
horizontally, which are capable of rotating on their longitudinal axes. One
roll is rotated directly and the other rotates freely. When material is placed
above the rolls it is drawn in through the nip and the second roll is rotated
b y friction.
Diameter of the rolls: Few centimeter up to several meters
The gap between the roll may be adjusted to control the degree of size
reduction.
Applications:
Used for crushing or cracking seeds prior to extraction of fixed oils or bruising soft tissues (often after cutting) to aid
solvent penetration.
HAMMER MILL
Method of size reduction: Impact

Hammer mill consists of a stout metal casing, enclosing a
central shaft to which four or more hammers are attached.
These are mounted with swivel joints, so that the hammers
swing out to a radial position when the shaft is rotated. The
lower part of the casing consists of screen through which
materials can escape, when sufficiently size reduced. The
material is collected in a container placed below the screen.
 The screen can be changed according to the particle size
required.
 According to the purpose of operation the hammers may be
square-faced, tapered to a cutting form or have a stepped-
form.
 The interior of the casing may be undulating in shape,
instead of smooth circular form for better impact.
 The rotor operates at a speed of 80cycles per second.

Advantages:
(a) It is rapid in action, and is capable of grinding many different types of materials.
(b) The product can be controlled by variation of rotor speed, hammer type and size and shape of mesh.
(c) Operation is continuous.
(d) No surface moves against each other so very little problem of contamination of mill materials.
Disadvantages:
(a) High speed of operation generates heat that may affect thermolabile materials or drugs containing gum, fat or resin.
(b) The rate of feed should be controlled otherwise the mill may be choked.
(c) Because of high speed of operation, the hammer mill may be damaged if some foreign materials like stone, metal
pieces etc. are present in the feed.
Applications: Powdering of crystals and filter cakes.
BALL MILL
Construction
The ball mill consists of a hollow cylinder rotated on its
horizontal axis. Inside the cylinder balls or pebbles are
placed.
Cylinder:
 Cylinder may be made up of metal, porcelain or
rubber.
 Rubber reduces the abrasion. Diameter of the cylinder
ranges from 1 to 3m in pharmaceutical practice.
Balls:
 Balls occupy about 30 to 50% of the volume of the
cylinder.
 Diameter of the balls depends on the feed size and diameter of the cylinder. The diameter of balls ranges from 2cm
to 15cm.
 Balls may be of metal, porcelain or pebbles.
Working Principle:
Larger particles are fed through an opening of the cylinder. The opening is closed. The cylinder is rotated at the critical
speed of ball mill. The optimum size reduction in a ball mill depends o the following factors:
Feed quantity:
Too much feed will produce cushioning effect and too little feed will produce loss of efficiency of the mill.
Speed of rotation of the cylinder:
 At low speed the mass of balls will slide or roll over each other and only a negligible amount of size reduction will
take place.
 At high speeds, balls
will be thrown out to
the wall of the cylinder
due to centrifugal force
and no grinding will
occur.
 At 2/3rd speed at which
centrifugation just
occurs is called the
critical speed of the
ball mill. At this speed
the balls are carried
almost to the top of the
mill and then fall in a cascade across the diameter of the mill. By this means the maximum size reduction is
obtained by impact of the particles between the balls and by attrition between the balls. Generally it is 0.5 cycles
per seconds (cps).

Advantages
1. It is capable of grinding a wide variety of materials of differing hardness.
2. It can be used in completely enclosed form, which makes it suitable for use with toxic materials.
3. It can produce very fine powders.
4. It is suitable both for dry and wet milling. Wet milling is required for preparation of pharmaceutical suspensions.
Disadvantages
1. Wear occurs from the balls and the inside surface of the cylinder hence there is possibility of contamination of
product with mill material. Abrasive materials increase wear.
2. Soft or sticky materials may cause problems by caking on the sides of the mill or by holding the balls in
aggregates.
3. The ball mill is a very noisy machine, particularly if the cylinder is made of metal.
Applications:
Large ball mills are used to grinding ores prior to manufacture of pharmaceutical chemicals. Smaller ball mills are used
for grinding of drugs or excipients or for grinding suspensions.
Various types of ball mills:

Hardinge mill: In this type of ball mills the cylinder has a conical end towards a discharge point. In this mill the larger balls remain
within the cylinder and the smaller balls are collected in the conical portion. As a result, coarser grinding takes place in the cylinder
portion and finer grinding takes place in the apex of the conical portion. The product is more finer and uniform than general
cylindrical ball mill.
Tube mill: They consist of long cylinder and can grind to a finer product than the conventional ball mill.
Rod mill: Instead of balls they contains rods, which extends the length of the mill. This rods are useful with sticky materials since
rods do not form aggregates like balls.
Vibration mill: In this type of mills vibratory movements are given instead of rotation. The cylinder is mounted on springs which sets
up vibration. The cylinder moves through a circular path with an amplitude of vibration up to abut 20mm and a rotational frequency
of 15 to 50 per second.
FLUID ENERGY MILL

Construction:
It consists of a loop of pipe, which has a diameter of 2 to 20cm. The height of the
loop may be up to 2m. Several nozzles are fitted at the bottom of the pipe. A
classifier is fitted at the product collection point.
Working principle
A fluid usually air, is injected at very high pressure through nozzles at the bottom
of the loop. This gives rise to a high velocity of circulation that produce turbulence.
Solids are introduced into the stream through the feed inlet. As a result of high
degree of turbulence, impacts and attrition occur between the particles. A classifier
is fitted in the system so that only finer size particles are collected as products and
the larger size particles are again sent to the stream of air for further size reduction.
The feed to the mill is previously size reduced and passed through a 100mesh
screen.
The size of the product may be 5m or below.
Advantages:
1. The particle size of the product is smaller than that produced by any other method of size reduction.
2. Expansion of gases at the nozzles lead to cooling, counteracting the usual frictional heat that can affect heat-
sensitive (thermolabile) materials.
3. Since the size reduction is by inter-particulate attrition there is little or no abrasion of the mill and no
contamination of the product.
4. For oxygen or moisture sensitive materials inert gases like nitrogen can be used instead of normal air.
5. This method is used where fine powders are required like micronization of griseofulvin (an antifungal drug),
antibiotics etc.

SIEVE ANALYSIS
Equivalent diameter
Sieve diameter, d s , is the particle
dimension that passes through a square
aperture (length = x).
ds
Range of analysis
The International Standards
Organization (ISO) sets lowest sieve x ds ds
diameter of 45m. Powders are usually
defined as particles having a maximum
diameter of 1000m, so this is the upper Sieve diameter, ds for various particle shapes
limit. In practice sieve analysis can be
done over a range of 5 to 125000m.
ISO Range : 45 to 1000 m
Range available in practice: 5 to 125000 m
Sample preparation
 Powders in dry state is usually used.
 Powders in liquid suspension can also be analyzed by sieve.
Principle of measurement with sieve

Sieve analysis utilizes a set of sieves. Each sieve is a woven, punched or electroformed mesh, often in brass or stainless
steel, with known aperture diameter which form a physical barrier to particles. In sieve analysis a set of sieves (known
as ‘stack’ or ‘nest’ of sieves) are arranged in such a way that the smallest aperture will be at the bottom and the largest
aperture will be at the top.
1. A sieve-nest usually comprises 6 to 8 sieves with an aperture progression based on 2 or 22 change in diameter
between adjacent sieves.
2. Initial weight (W0) of powder sample was taken on the first sieve (i.e. topmost sieve). The sieve-set was closed and
shaking was started. After shaking for a stipulated time, the sieve-set was taken out. All the sieves were
disassembled.
3. The powder retained on each sieve was collected on a paper (bearing the mesh number) and weighed.
TABLE - 1
Sieve number Size of Arithmetic mean Weight Retained % Retained Cumulative
(Passed/ opening Size of openings on smaller sieve on smaller % oversize
Retained) (Passed / d (m) (gm) sieve
Retained)
M1/M2 d1/d2 ½(d1 + d2) W1 p1=100w1/W p1
M2/M3 d2/d3 ½(d2 + d3) W2 p2=100w2/W p1+p2
M3/M4 d3/d4 ½(d3 + d4) W3 p3=100w3/W p1+p2+p3
-- -- -- -- -- --
-- -- -- -- -- --
-- -- -- -- -- --
Total = W Total = 100
TABLE – 2: Plot
log d Weight % Cumulative
retained % oversize
Weight % Cumulative
retained Weight %
retained
log d log d

STANDARDS OF SIEVES 25.4 mm

It is required that wire-mesh sieves will be made from (1 inch)
wire of uniform, circular cross-section and for each
sieve the following particulars are stated: wire
Number of sieve diameter
This is the number of meshes in a length of 25.4mm
(i.e. 1 inch), in each direction.
25.4 mm
Nominal size aperture (1 inch)
This is the distance between the wires, so that it
represents the length of the side of the square aperture.
N.B. While it is the diameter of the largest sphere that would

pass the mesh, it is not necessarily the maximum dimension
of the particle, plate like particles will pass through
diagonally and long fibrous particles require only suitable 5 mesh
orientation. sieve
Nominal diameter of the wire
The wire diameter is selected to give a suitable aperture size. It is also required to give the
necessary strength to avoid distortion.
The diameter of the wire is represented by Standard Wire Gauge.
Approximate screen area

This standard expresses the area of the meshes as a percentage of the total area of the sieve.
It is governed by the diameter of the wire. It is generally kept within 35 to 45% of the total Nominal aperture
area of the sieve.
This represents the useful area of a sieve. Greater screen area is preferred.
Total sieve area - Area occupied by the wire
Approximate Screen Area  x 100%
Total area of the screen
Aperture tolerance average
Some variation in the aperture size is unavoidable and this variation is expressed as a percentage, known as aperture
tolerance average. It is the maximum limit within which the dimension of meshes can be allowed to vary and still be
acceptable for sieving.
Finer wires are likely to be subject to a greater proportional variation in diameter than coarse mesh. Hence, the aperture
tolerance average is smaller for sieves of 5 to 10 mesh than in case of 300mesh.
Tyler Standard Screen Scale
Mesh Clear Opening, mm Wire Diameter, mm

3 6.680 1.778
4 4.699 1.651
6 3.327 0.914
8 2.362 0.813
10 1.651 0.889
14 1.168 0.635
20 0.833 0.437
28 0.589 0.318
35 0.417 0.310
48 0.295 0.234
65 0.208 0.183
100 0.147 0.107
150 0.104 0.066
200 0.074 0.053

SIZE SEPARATION EQUIPMENTS
SHAKING SCREEN
Principle:
Particles of different sizes are separated by passing them Feed
through a sieve, which oscillates to-and-fro Hanger
continuously.
Construction: Screen
Shaking screen consists of metal frame to which a screen
is fixed at the bottom. The screen cloth may be riveted . .
Frame
directly or fitted by using a removable bolted frame. The
metal frame is suspended by hanger rods, so that it can
move freely. The metal frame may be suspended either Eccentric on a To-and-fro
horizontally or in inclined position. One side of the rotating shaft motion
frame is attached with an ordinary eccentric on a rotating Product
shaft. The entire frame experiences a reciprocating (to-
and-fro) motion. Fig. Shaking screen
Working:
The screen is allowed to shake in a reciprocating motion. The feed (material to be screened) is introduced on to the
screen from a side. . Fine particles are screened off initially. The remaining materials moves forward and the over-sized
particles are collected at the other end.
Advantages:
It requires low-head room and low power requirement.
Disadvantages:
High cost of maintenance of screens and supporting structures.
Its capacity is low.
SHAKING AND VIBRATING SCREENS (ROTEX SCREEN)

Principle: Rotex screen works on oscillating
agitation (to-and-fro motion) by means of an Wooden Rubber
eccentric mechanism. Further vibrations are Block ball
caused by rubber balls. Screen of
Construction: certain size
This equipment consists of a set of screens, Supporting
which are slightly inclined at 5 degrees with screen (Coarser
horizontal axis. Each screen set is double layered. Feed than above screen)
The upper screen is of a fixed size and the lower
Fine Wooden Ruber
one is coarser screen, which is a supporting sieve.
Coarsest screen block ball
Between these two screens, wooden blocks are
placed at different intervals. Between the wooden screen
blocks rubber balls are placed. This two-sieve
system represents one unit. Several such units are
arranged in the descending order, i.e. sieve or
. .
larger size opening remains at the top and finer
size opening remains at the bottom. The overall
Eccentric
assembly of screens is supported on sliding
assembly
contacts at the lower end. The upper end of the To-and-fro
screen system is connected to an eccentric pin on motion
a flywheel.
Fine Coarse
Working:
size size
The screen system is allowed to agitate with the
help of eccentric. The shaking motion of the Fig. Rotex Screen
screen causes the balls to fly between the screens.
As they strikes the inclined surface of the wooden blocks, the balls deflect upward and strike the screen cloth and thus
prevents blocking of the mesh. The feed is introduced at the higher end of the screen. The material passes through the
upper screen and reaches the next screen. This process continues until all the materials are separated into fractions. The
fractions are collected separately at the outlet point.
Uses: Rotec screen is used for handling a variety of dry powders, granules and dry foods.

GYRATORY SCREENS (FINEX)

Principle:
The Finex shifting machine consists of a horizontal screen to which a
gyratory movement of great intensity and small amplitude is imparted by Screen
eccentric mechanism. Every particle is given a rotary movement on one
axis and a second rotary movement on an axis at right angles to the first.
Construction: Clearing Screen
Screens are fitted horizontally. The topmost has the largest opening and gates
the bottom one will have finer opening. The overall assembly is given a
gyratory motion by eccentric mechanism. Clearing gates are fitted at one
side of the periphery.
Working:
The feed is introduced at the center of the screen and the gyratory
motion drives the larger sizes to the periphery of the screen where it is Fig. Gyratory Screens
discharged through a clearing gate set in upright side of the sieve. In
some devices a spiral strip of metal is welded to the screen. The larger size passes progressively from the center to the
periphery.
Fluid
CYCLONE SEPARATOR outlet
Principle
In cyclone separator centrifugal force is used to separate solid from Tangential
fluids. The separation process depends on particle size and particle inlet
density. It is also possible to allow fine particles to be carried with the
fluid.
Construction
It consists of a short vertical, cylindrical vessel with a conical base. The
upper part of the vessel is fitted with a tangential inlet. The solid outlet is
at the base. Fluid outlet is provided at the center of the top portion,
which extends inwardly into the separator. Such an arrangement prevents
the air short-circuiting directly from the inlet to the outlet of the fluid.
Working
The solids to be separated are suspended in a stream of fluid (usually air
or water). Such feed is introduced tangentially at a very high velocity, so Solids
that rotary movement takes place within the vessel. The centrifugal force outlet
throws the particles to the wall of the vessel. As the speed of the fluid
(air) diminishes, the particles fall to the base and collected at the solid Fig. Cyclone separator
outlet. The fluid (air) can escape from the central outlet at the top.
Uses
1. Cyclone separators are used to separate solid particles from gases. Rotating
2. It is also used for size separation of solids in liquids. shaft
3. It is used to separate the heavy and coarse fraction from fine dust.
Feed Feed
Fan blade
AIR SEPARATOR
Principle
Settling
The cyclone separator alone cannot carry out size separation on fine
chamber
materials. For such separations a current of air combined with centrifugal
force is used. The finer particles are carried away by air and the coarser
particles are thrown by centrifugal force, which fall at the bottom.
Rotating
Construction
plate
It consists of a cylindrical vessel with a conical base. A rotating plate is
fitted on a shaft placed at the center of the vessel. A set of fan blades are
also fitted with the same shaft. At the base of the vessel two outlets are
provided: one for the finer particles and the other for coarse particles.
Working Coarse
Fine particle
The disc and the fan are rotated by means of a motor. The feed (powder) particle outlet
enters at the center of the vessel and falls of the rotating plate. The rotating outlet
fan blades produce a draft (flow) of air in the direction as shown in the Fig. Air separator
diagram. The fine particles are picked up by the draft of air and carried
into space of settling chamber, where the air velocity is sufficiently reduced so that the fine particles are dropped and
removed through the fine particle outlet.
AMAR RAVAL EMAIL ID Pharmarocks77@gmail.com HELPLINE (+91) 9016312020 10 | P a g e
Particles too heavy to be picked up by the air stream are removed at the coarse particle outlet.
Uses
Air separators are often attached to the ball mill or hammer mill to separate and return over sized particles for further
size reduction.
BAG FILTER Discharge

Principle manifold
In a bag filter, size separation of
fines (or dust) from the milled
Bell-Crank
powder is achieved in two steps. In
Lever
the first step, the milled powder is
Assembly Metal
passed through a bag (made from
cloth) by applying suction on the casing
opposite side of the feed entry. This
facilitates the separation. In the next
step, pressure is applied in order to Filter
shake the bags so that powder bags
adhering to the bag falls off, which
is collected from the conical base. Feed Air
inlet outlet
Construction
It consists of a number of bags made
of cotton or wool fabric. These are
suspended in a metal container. A
hopper is arranged at the bottom of Dust hopper
the filter to receive the feed. At the
top of the metal container, a Product Product
provision is made for vacuum fan Discharge Discharge
and exhaust through discharge (Closed) (Opened)
manifold. At the top of the vessel a (b) Shaking Period
(a) Filtering Period
bell-crank lever arrangement is made
to change the action from filtering to Fig. Bag filter
shaking.
Working
(a) Filtering period: During this period the vacuum fan produce a pressure lower than the atmospheric pressure within
the vessel. Gas to be filtered enters the hopper, passes through the bags, and out of the top of the apparatus. The
particles are retained within the bags.
(b) Shaking period: During this period the bell-crank lever first close the discharge manifold and air enters through the
top so the vacuum is broken. At the same time it gives a violent jerking action to the bags so that they are freed
from the dust. The fine particles are collected at the conical base.
Uses
1. Bag filters are used along with other size separation equipment, e.g. a cyclone separator.
2. They are use on the top of fluidized bed dryer for drying to separate the dusts.
3. They are used to clean the air of a room.
4. Household vacuum cleaner is a simple version of bag filter.
COTTRELL PRECIPITATOR
Principle
If a gas is subjected to a strong unidirectional electrostatic field, the gas become ionized and drifts toward one
electrode. If a finely divided solid particle (or liquid droplet) is suspended in the gas, the particle (or droplet) will
become charged and will drift toward the same electrode as the ionized gas.
Construction
There will be two electrodes: (i) Discharge electrode and (ii) Collecting electrode.
 The discharge electrode is usually a wire, chain, wire screen or other arrangement with a large surface.
 The collecting (or smooth) electrode may be parallel plate or pipe.
 In case of parallel plate design the gas flows parallel to plates.
Plate dimensions: Length = 10 to 18 ft Width = 3 to 6 ft.
 In case of pipe design the pipes are placed vertically and a wire (discharge electrode) is fitted at the center of the
pipe. Gas flows from the bottom to the top of the pipe. At the bottom of the pipe a hopper is given to collect the
particles. Pipe dimensions: Height 6 to 15 ft.

Working
AC current is first stepped up Discharge electrode
with a step up transformer to (wire)
raise the potential difference to
50,000 to 60,000 volts. Then
the voltage is made
Discharge electrode
unidirectional by a motor-disc
(wire sreen)
assembly where the motor is
rotating at a speed similar to
the frequency (i.e. cycles per
second or Hz) of the AC
current. This results in a Collector electrode
pulsating but unidirectional Collector electrode (Pipe)
electrostatic field. (Plate)
The particles will be charged
and precipitated on the smooth Discharge Electrode
plate or pipe, which is then Flow of gas AC to DC
collected through the hopper. DC converting AC AC (230V)
Use motor
The Cottrell process is Solid Particle or 50,000V 50,000V
successfully used for the Droplet of liquid
removal of fine dusts from all Step up
kind of waste gases. Collector Electrode
AC Transformer
SCRUBBERS
Fig. Cottrell Precipitator
Principle
Solid and liquid particles suspended in
gas can be removed (or scrubbed) by
Dust free Entrainment
introducing water from the top of the
gas outlet separator
equipment and gas through the bottom
of the equipment, i.e. water and gas Water inlet
flow in counter-current flow. Deflector cone
Construction
This equipment consists of a Stationary vane
cylindrical shell with conical bottom.
The gas containing the suspended Annular
particles enters through a tangential shelf
inlet at the bottom. Deflector cones are
placed on stationary vanes. These Fig. A contact Dust laden
air inlet
vanes are placed on annular shelves.
One deflector cone, vanes and the
annular ring as a whole called a
contact. There are several such
contacts placed inside the shell. The Dust-water
liquid inlet is placed at the second top outlet
contact. The topmost contact is called
entrainment separator. Dust collector Fig. Scrubber
outlet is placed at the bottom of the equipment. The gas is taken out through the gas outlet placed at the top of the
separator.
Working
The gas carrying the particles (or droplets) are introduced through the gas inlet at the bottom and passes upward
through the vanes under deflector cones. Liquid (e.g. water) is introduced from the top. It falls on the conical deflector
and flows over the vanes to produce a curtain of liquid. The gas passes through these curtains. Particles or droplets are
retained in the liquid and gas passes to the next contact. After passing through several such contacts the gas passes
through the entrainment separator where small droplets of water (known as entrainment) are separated and the gas
leaves the separator through the gas outlet. The discharged gas goes to a cyclone separator where the entrained water (if
any) are finally removed from the gas.
Use
To clean the dust of air before entering inside a room or before discharging a gas in the environment from an industry.

SIZE SEPARATORS BASING ON SEDIMENTATION THEORY

Size separation by sedimentation utilizes the differences in settling velocities of the particles with different diameter (d)
and these can be related to Stoke’s law.
Stoke’s law
When a solid particle is suspended in a liquid the particle settles downward at a velocity, V. This velocity is called
sedimentation rate. It is found that this rate of sedimentation depends on the diameter of the particle, density of the
liquid and particle, viscosity of the liquid and the acceleration due to gravity. All this parameters can be combined in
the form of Stoke’s equation:
Where d = diameter of the particle
d 2 ( 1 -  2 )g 1 = density of the particle
V
18 2 = density of the liquid
g = acceleration due to gravity
CONTINUOUS SEDIMENTATION TANK  = viscosity of the liquid.
Liquid Liquid
A shallow tank is arranged with inlet and outlet pipes as inlet Flow of fluid outlet
shown in the figure. Particles entering the tank will be
acted upon by a force that can be divided into two
Gravity Trajectory
components:
of the particle
(i) a horizontal component due to the flow of
liquid carrying the particles forward and
(ii) a vertical component due to gravity, which Larger Particles Smaller Particles
causes the particles to fall towards the bottom
of the tank. This component is governed by
Stoke’s law so that the velocity of
sedimentation is proportional to the square of Fig. Sedimentation Tank
the diameter of the particles.
Thus the particles will settle at the bottom of the tank in such a way that the coarsest (largest) particles will settle near
to the inlet of liquid and the finest particles near to the outlet of the liquid. Partitions are arranged at the floor of the
tank to enable collection of different size fraction particles.
Handle wheel
DOUBLE CONE CLASSIFIER Inner cone Discharge
Principle Launder
The separation takes place by elutriation principle.
N.B. In sedimentation method the fluid is stationary and the separation is
taking place by the velocity of the particles. In elutriation method the liquid Fine particle
is flowing to the opposite direction of the sedimentation of the particle. Feed Feed
In elutriation method the fluid flows in opposite direction to
the sedimentation movement. In this equipment the liquid
moves upward. If the sedimentation velocity of a particle is Outer cone
less than the velocity of the liquid then the particle will
move upward. If the sedimentation velocity of the particle is
more than the velocity of the liquid then the particle will
move downward. So if the velocity of the liquid is kept
within the sedimentation velocities of the coarse and fine
particles then the finer particles (has lesser sedimentation
velocity) will move upward and the coarser particles (have Liquid inlet
Discharge Box
greater sedimentation velocity) will move downward.
Construction Coarse Particle
Two cones of different sizes are placed one in another. At Outlet
the top of the outer cone a discharge launder is fitted at the
outside surface of the outer cone. Water inlet is provided at Fig. Double cone classifier
the bottom of the equipment. The inner cone is shorter than the outer cone. The inner cone can be moved along its
vertical axis with the help of a hand wheel. At the bottom a collecting box is provided to collect the coarse particles.
Working
The feed enters the inner cone and water is introduced through the water inlet at the bottom. The particles settle from
the inner cone meet a rising stream of water at lower end of inner cone. The fine particles pass upward and are collected
in the discharge launder. The coarse particles settle into the collecting box for coarse material and are drawn off at
intervals.
The degree of separation is regulated by the velocity of water supply and the height of the inner cone regulated by the
hand-wheel.

FORMULATION AND EVALUATION OF
VARIOUS COSMETIC AND DENTAL
PRODUCT
1) DEFINITION:-
The term cosmetics have been derived from the term “COSMETIKOS” which means the
skill to decorate. Thus cosmetics is the art of decorating yourself to look
beautiful.
According to D & C Act:-
Cosmetics mean any articles meant to be rubbed, poured, sprinkled or sprayed on or
introduced into or otherwise applied to any part of the human body for cleansing,
beautifying, promoting attractiveness or altering appearance and include any article
intended for use as a component of cosmetic. Soap is not covered under cosmetic
product.
2) CLASSIFICATION OF COSMETICS:-
3) INGREDIENTS OF COSMETICS:-
1. Water
2. Oils, Fats, Waxes
3. Humectants
PHARMAROCKS: THE WAY OF SUCCESS MR. AMAR M. RAVAL (9016312020)

4. Surfactants
5. Preservatives
6. Perfumes And Colors
7. Herbal Or Plant Material
8. Functional Raw Materials
1. WATER:-
It is the main ingredient of cosmetics formulation. Thus stability and quality of final product is
dependent on the purity of water used so pure water should be used in manufacturing of
cosmetics. Pure water on large scale can be manufactured by any of the methods mentioned
below.
 Ion exchange system
 Distillation
 Reverse osmosis
2. OIL, FATS and WAXES:-

These are used in preparation of creams, lotions, brilliantine, hair oil, lipsticks etc. The source
of oil, fat & wax can be mineral source & animal source. The source and example is given
below.
Source:-1) Mineral source
-mineral oil
-paraffin and petroleum jelly
2) Animal source
-wool fat
-bees wax, Spermaceti
OILS:-
Name of oil
(Vegetable)
Use in cosmetics
Almond Creams (emollient)
Arachis Hair oil, Brilliantines
Castor Lip stick, hair oil cream ,lotion
Olive Bath oils ,creams lotions
Type of mineral oil Use in cosmetics product
Light liquid paraffin In bath oil, hair oil,lotions,creams,brilliantine
In bath oil, hair oil,lotions,creams,brilliantine

Heavy liquid paraffin
(emollient)
• waxes:- The commonly used waxes in preparation of cosmetics Include bees wax,
spermaceti,ceresin,ozokerite wax
3. HUMECTANTS:-
This is added to prevent drying out of cosmetics
(e.g. o/w creams)
Type of Humectant
Examples
1.Inorganic Calcium chloride (not used now due to compatibility problems)
Sodium lactate (used in sunscreen lotions)

2.Metal organic
Polyethylene glycol, Propylene glycol, glycerol, sorbitol, mannitol,

3.Organic
glucose
4. SURFACTANTS:
Surfactants lower one or more boundary tensions at interface in the system. one common
feature of surfactant is that they all are amphipathic molecules containing a hydrophobic part
& a hydrophilic part. Used in cosmetics to impart following functions:.
DETERGENCY, WETTING, FOAMING, EMULSIFICATION, SOLUBILIZATION
Surfactants on basis of their ionic behavior can be divided into following 4 types:-
Type of surfactant Examples

Fatty acid soaps, alkyl sulphates, alkyl sulphonates, polyethylene glycol
1.Anionic
ester,alkyl ether sulphates taurines,sarcosinates etc.
Alkyl trimethyl ammonium salts, Dialkyl dimethyl ammonium salts alkyl
2.Cationic
pyridinium salts, quaternised diamine salts.
Alkanolamides,alkyl polyglycol ether, thioethers,
3. Non ionic
alkyl polyethyleneimine amides.
4.Ampholytic Betains, alkylimidazolines, acyl peptides,etc.
5. PRESERVATIVES:-
Used to prevent spoilage which occurs due to
1) Oxidation of oils 2) Microbial growth
• Unused cosmetics are usually contaminated wit PSEUDOMONAS but used cosmetics
are contaminated with STAPHYLOCOCCI,FUNGI,YEAST
• Types of preservatives :-
1) Anti microbial agents:- e.g. .Benzoic acid, formaldehyde, cresol, phenol,
thiomersol,phenyl mercuric salts. Etc.
2) Antioxidants :- Gallic acid, methyl gallate,BHA,BHT,Tocopherol, citric
acid,Ethanolamine,lecithin,ascorbic acid, sodium sulphite,
Sodium metabisulphite
3) Antioxidant synergists: - Enhance the efficacy of antioxidants. examples
include:-ascorbic acid, citric acid, phosphoric acid
4) UV absorbers:-These are mainly used in products which are vulnerable to
visible or UV light. By incorporating UV absorbers colorless containers can be
used if deterioration is due to UV light only.

6. PERFUMES:-
The word perfume has been derived from “per” means through and “fumum” means smoke.
It suggests that early perfumes were pleasant smells obtained by burning wood
and grass etc.
Source of perfume Example

Natural
Musk ,civet, Ambergris, Castroreum etc.
(Animal source)
Natural
Rose ,jasmine, lemon, lavender etc.
(Plant source)
Aroma chemical Eugenol, Farnesal, Rose oxide, Citral ,Limonene
Floral base Rose base, Jasmine base
Citrus base(in colognes),spice base, oriental base,
Woody base
fruity base ,etc
7. COLORS:-
It defined as visual sensation caused by a definite wavelength by an object by one/more
phenomenon of emission, reflection, refraction, transmission.
Colors can be classified into three classes:-

a) Natural colors:- Plant source :- e.g. Saffron, turmeric
Animal source:-e.g. Cochineal (red)
b) Inorganic colors:- e.g. Iron oxides, chromium oxides, carbon black, titanium dioxide,
zinc oxide etc.
c) Coal tar colors:-Tartrazine, amaranth, Erythrosine, Indigocarmine. etc.
8.HERBAL OR PLANT MATERIAL:-

These herbal or plant materials are used in different cosmetics preparations.
NAME USE IN COSMETICS
Almond Facial and body scrubs
Azadiracta Tooth paste and skin care
Comfrey Creams and lotions
Tulsi Skin cream and lotions
Cucumber Masks, toner, cleanser
Henna Dyeing of hair
Amla Shampoo
Jasmine Hair oil
Lemon Skin tonic, cleansers

Apricot Facial and body scrubs
9. FUNCTIONAL RAW MATERIALS:-

These agents contribute towards some functional property .
TYPE EXAMPLE & USE
Vit C (antioxidant in emulsion),vit A,

VITAMINS Vit E (skin beautification)
AV HILL MP TT
AMINO ACIDS
(all essential amino acids)
ANTI INFLAMMATORY Allantoin (hand cream & lotion) Cade oil(eczema&

AGENTS psoriasis),Calamine
SUNSCREEN PABA, Vitamin C, Quinine salts

AGENTS Coumarin derivatives
ANTIDANDRUFF Selenium, cadmium sulphide, ZPTO
(4) FORMULATION
 COSMETICS FOR SKIN
Function:-
1) To provide decoration
2) To supplement natural functions of skin
Type of cosmetics used for skin:-

1. Skin cream
2. Lotion
3. Face powder & Compacts
4. Skin colorants
5. Body powder
6. Face pack & Masks
7. Bath Preparations (bath salt,oil,powder,foam)
8. Astringents &Skin tonics (antiperspirants, astringent lotion, preshave & after shave
lotion, colognes)
1. CREAMS: - These are the solid or semisolid preparation which is either a o/w or w/o
type emulsion.
TYPES OF CREAMS:
A. Cleansing cream
B. Massage creams
C. Night creams
D. Moisturizing creams

E. Foundation creams
F. Vanishing creams
G. All purpose creams
A) CLEANSING CREAM:- Cleansing cream is required for removal of facial make up, surface
grime, oil, water and oil soluble soil efficiently mainly from the face & throat.
Characteristic of a good cleansing cream:-

1) Be able to effectively remove oil soluble & water soluble soil, surface oil from skin.
2) Should be stable &have good appearance.
3) Should melt or soften on application to the skin
4) Should spread easily without too much of drag.
5) Its physical action on skin & pore openings should be that of flushing rather than
absorption
Type of cleansing cream:-

I.) Anhydrous type:- It contains mixture of hydrocarbon, oils and waxes. It also
contains cetyl alcohol, spermaceti, cocoa butter, fatty acid esters etc. Not
popular.
Mineral oil-80 gm, Petroleum jelly– 15gm
Ozokerite wax -5 gm Preservative and perfumes –q.s
Note :- Formation crusty surface is avoided by adding Ozokerite & petrolatum

(prevent bleeding of mineral oils.)
Opaque character obtained by adding Zno, mg.stearate, Tio2
II.) Emulsified type:- They can be either o/w or w/o type.

Common Ingredients:-
Oil phase…………………..Spread easily
Waxes……………………..Give appropriate thixotropy
Emollient material…………likes cetyl alcohol, spermaceti, lanolin
Water phase with preservative
Different types:-
(1) Cold Cream:- Cooling effect is produced due to slow evaporation of the water
contained in the formulation. These are w/o type.
(2) Beeswax Borax type:- These contain high percentage of mineral oil. These are o/w
type. This cream contains high amount of mineral oil for cleansing action. Basically
these are o/w type emulsion. After the cream is being rubbed into the skin sufficient
quantity of water evaporates to impart a phase inversion to the w/o type. The
solvent action of the oil as external phase imparts cleansing property. In this type of
cream borax reacts with free fatty acids present in the bees wax and produces soft
soap which acts as the emulsifying agent and emulsifies the oil phase .
A typical formulation:-
Bees wax -2 gm Borax-2 gm
Almond oil -50 gm Rose water 35.5 gm
Lanolin– 0.5gm preservative and perfume –q.s

B) NIGHT & MASSAGE CREAM:-
These are generally applied on the skin and left for several hours say overnight and assist
in the repair of skin which has been damaged by exposure to various elements or exposure to
detergent solution or soap. The mostly have a moisturizing & a nourishing effect of affected
skin. These also contain vitamins and hormones basing on the application. This cream give
better look to the skin and prevent dryness.
A typical formulation
• Mineral oil-38gm Borax 1gm
Petroleum jelly-8gm Water 35gm
White bees wax-15gm Perfume & preservative q.s
Paraffin wax – 1.0gm
Lanolin 2gm
C) VANISHING CREAM:-
These are named so as they seem to vanish when applied to the skin. High quantity of stearic
acid as oil phase used.This provides an oil phase which melts above body temp, and
crystsllises in a suitable form, so as to invisible in use and give a non greasy film.
• Main component is emollient esters ,stearic acids
• Part of stearic acid is saponified with an alkali & rest of stearic acid is emulsified this
soap in large quantity of water.
• The quality of cream depends on the amount of acid saponified & nature of alkali
used.
• NaoH makes harder cream than koH.
• Borax makes cream very white but product has tendency to grain.
• Pearliness can be attained using liq.paraffin, cocoa butter, starch, castor oil, almond
oil.
• Ammonia solution has a tendency to discolor creams made with it after some time.
• Cetyl alcohol improves texture and stability at low temperature without affecting
sheen.
Stearic acid 15gm Glycerin 5gm
KOH 0.5 gm water 75.82 gm
NaOH 0.18 gm preservative &perfume q.s
Cetyl alcohol 0.50 gm
Propylene glycol 3.0gm
Stearic acid has whiteness like snow so some times the preparation is called as
SNOW.
D) FOUNDATION CREAM:-
• Applied to skin to provide a smooth emollient base or foundation for the application of
face powder & other make up preparations. They help the powder to adhere to skin.
They are almost o/w type.
Types:
1) Pigmented
2) Unpigmented
• Lanolin 2 gm Propylene glycol 8gm

• Cetyl alcohol 0.50 gm water 79.10 gm
• Stearic acid 10gm Perfume &preservative q.s
• KoH 0.40 gm
E) HAND & BODY CREAM:-
• The repeated or constant contact with soap and detergent damages & removes film of
sebum thus this cream is used to impart following functions to the skin.
• The function of these creams are
- Replace/reduce water loss.
- Provide oily film to protect the skin.
- Keep the skin soft, smooth but not greasy.
Type:-
a) Liquid cream:-consistency is of liquid nature
b) Solid creams:- Consistency is higher
c) Nonaqueous type:-Not containing any aqueous medium.
a.) Isopropyl myristate - 4 gm
Mineral oil -- 2 gm
Stearic acid – 3.gm
Emulsifying wax - .275 gm
Lanolin - 2.5 gm
b.) Glycerin -3.0 gm

Triethanolamine – 1 gm
Water -84.225 gm
Perfume and Preservative -q.s
(F) ALL PURPOSE CREAMS:-

All purpose means it is suitable for hands, face and body. They are w/o types.
Formula:- Oil phase Water phase
Mineral oil 18% Water 61.3%
Lanolin 2% Glycerol 5%
Petroleum jelly 2% Magnesium sulphate 0.2%
Ozokerite 7 % Perfume, preservative q.s
Paraffin wax 3%
2) LOTIONS:-
(I) Cleansing lotion
Mineral oil 38%,
Bees wax 2%,
Triethanolamine stearate 8%,
Water to make 100%
Preservative & Perfumes –q.s

Note: - Triethanolamine discolors on standing so it should be made in situ using calculated
amount of stearic acid and Triethanolamine. O/W lotion have tendency to increase in viscosity
with ageing (this is prevented by using ethoxylated cholesterol)
(II) Sunscreen lotions:-

These lotions have property of protecting the skin from sun burning.
An ideal sunscreen agent should have following properties.
 Absorb light over the range of 200-400 nm.
 Be stable to heat, light & perspiration
 Be nontoxic & nonirritant
 Not be rapidly absorbed
 Be neutral
 Be readily soluble in suitable vehicles.
US dept of health has recommended following ingredients to be used as sunscreen
agents. They absorb U.V radiation.
 CYCLOFORM
 MONOGLYCERYL PARA AMINO BENZOATE
 DIGALLOYL TRIOLEATE
 BENZYL SALICYLATE
 BENZYL CINNAMATE
And few others are PABA, cinnamic acid derivatives, coumarin derivatives, Quinine salts,
uric acid derivatives.
Glyceryl p-amino benzoate 3.0 %
Glycerin 5.0 %
Alcohol 10 %
Methyl cellulose 0.5 %
Perfume q.s
Water to make 100 %
3. POWDERS:-
These are categorized as face powder, body powder, and Compacts.
The powders should have following properties:-
 Must have good covering power so can hide skin blemishes.
 Should adhere perfectly to the skin & not blow off easily.
 Must have absorbent property.
 Must have sufficient slip to enable the powder to spread on the skin by the puff .
 The finish given to the skin must be preferably of a matt or peach like character.
The raw materials used to manufacture of various powders are classified with example as
follows:-
RAW MATERIAL FOR POWDER
EXAMPLE
IMPARTING
Covering prop Titanium dioxide,zno,kaolin,zn stearate
Adhesion prop Mg.stearate,talc,mg & ca salt of myristic acid

Slip & Softness Zn/mg undecanate,aluminium hydrosilicate
Absorbency prop Starch, colloidal kaolin,bentonite,pptd chalk
Peach like finish Rice starch,silica,powdered silk
Frosted look Guanine, bismuth oxychloride,mica,Zn,Al
Color & perfumes Iron oxides
FACE POWDER:-
Types of Face Powders:-
A. Loose face powder
B. Compact face powder
C. Talcum powder
D. Baby powder
A) LOOSE FACE POWDER :-

The essential feature of a good face powder includes Covering power, slip, Adhesiveness,
Absorbency, Bloom, Coloring, Perfuming.
Type:-
b) Light type
c) Medium type
d) Heavy type
Type of face powder purpose & composition
LIGHT Dry skin, contains large amount of talc
MEDIUM Normal or moderately oily skins, lesser talc & zinc oxide
HEAVY Extremely oily skins ,low talc but higher amount of Zinc oxide
TYPICAL FORMULATION OF FACE POWDERS:-
LIGHT POWDER MEDIUM POWDER HEAVY POWDER

Talc ---------63gm Talc---------39.7gm Talc---------20.0gm
Kaolin --------20 gm Kaolin-------39.5 gm Kaolin(light)-20 0gm
Cal. carbonate(l) 5 gm Cal. carbonate(l) 5 gm . Cal. carbonate(l) 39 g
Zinc oxide ---5.0gm Zinc oxide ---7.0gm Zinc oxide ---15.0gm
Zinc stearate-5.0gm Zinc stearate-7.0gm Mg.stearate—5.0gm
Mg.carbonate—1.0gm Mg.carbonate—1.0gm Color ------0.5gm

Color ------0.5gm Color ------0.2gm Perfume------0.5gm
Perfume------0.5gm Perfume------0.6gm
B) COMPACT FACE POWDER:-

It is a dry powder which has been compressed into a cake. The pressure for compaction is
very important. The powder must come off easily when rubbed with puff.
Type of binder Examples

1) Dry binder Zn/Mg.stearate
2) Oil binder (water repellant ) Mineral oil, isopropyl myristate, Lanolin derivative
3) Water soluble binder PVP, CMC, Cellulose, Acacia, Tragacanth
5) Emulsion binder Triethanolamine stearate, Glycerol monostearate
(C) TALCUM POWDER:- It is used as an adsorbent for making the skin from the excess
moisture. Light magnesium carbonate added to mix perfume.
Formula:- Zinc oxide ………………………. .. 50
Zinc stearate ……………………… 50
Chlorhexidine diacetate ………3
Light magnesium carbonate.100
Talc ……………….797
Perfume……………………….0.2
D) BODY POWDER:-
It consists of mainly talc, with small portion of a metallic stearate, precipitated chalk,
magnesium carbonate(light). Talcum/body powders containing antiseptic substances are also
used for prickly heat, and fungus infections. Boric acid act as antiseptic.
Talc - 75 gm Aluminum stearate – 4 gm
Colloidal Kaolin –10 gm Boric acid – 0.3 gm
Colloidal silica--- 5 gm Perfume --- 0.7 gm
Magnesium Carbonate- 5 gm
3. SKIN COLORANTS:-
It includes a) Lipsticks
b) Rouge
a) LIPSTICK:-These are basically dispersions of coloring matter in a base consisting of a
suitable blend of oils, fats, and waxes suitably perfumed and flavored molded in the form of a
stick.
Ideal character of lipstick includes:-

 Should cover the lips adequately with some gloss and last for long time.
 It should make the lips soft.
 The film must adhere firmly to the lips without being brittle.& tachy.
 Should have high retention of color intensity without any change in shade.
 Should be completely free from grittiness & free from drying.
 Nonirritating to the lips.
 Desirable degree of plasticity & have a pleasant odor and flavor.
• Classification of raw materials:-

1) Wax mixtures (bees, candeilla, carnauba, ceresin, Ozokerite wax)
2) Oil mixtures (castor, paraffin, THFA, isopropyl myristate)
3) Bromo mixture
4) Colors
5) Preservatives
Types of lipsticks
1) Transparent lipstick
2) Liquid lipstick
3) Lip rouge
4) Lip jelly
5) Lip salve
6) Lip glosses
A typical formulation of lipstick.

Castor oil 54 gm
Lanolin (anhydrous) 11 gm
Candeilla wax 9 gm
Isopropyl myristate 8 gm
White beeswax 5 gm
Carnauba wax 3 gm
Ozokerite wax 3 gm
Eosin 2 gm
Lakes 5 gm
Rose flavor q.s
Antioxidant q.s
Preservative q.s
b) SKIN ROUGE: - These are the cosmetics preparations used to apply a color to the cheeks.
The color may vary from the palest of pinks to the deep blue reds .The tint or color may be
achieved using water insoluble colors such as iron oxides and certain organic pigments or by
using water soluble organic colors which actually stain the skin.
Types :-
 Powder rouges
 Wax based rouges (Stick rouge)
 Emulsion cream rouges
 Liquid rouges

Powder Rouges Stick rouge

Talc…………………………….40 Carnauba wax…………………3
Zinc oxide……………………..10 Candelilla………………………6

Magnesium carbonate……….20 Ozokerite………………………1.5
Pigment………………………..14 Bees wax………………………1.5
Lanolin………………………...30 Hexadecyl stearate……………10
Perfume………………………..2 Isopropyl myristate…………….8
Castor oil……………………….65
BHA……………………………..0.02
Color……………………………5
Emulsion cream rouge (vanishing type) Liquid rouge

Stearic acid…………………….15 (A) Iso stearic acid…………….0.02
Potassium hydroxide………….0.5 Mineral oil………………….30
Sod. Hydroxide………………..0.18 Iso propyl myristate………..5
Glycerin………………………..8 Colloidal silica……………..1
Water…………………………..76 Color………………………...3
Pigment, Perfume & (B) Water………………………..48.3
Preserative……………………q.s Triethanolamine……………4
Perfume…………………….0.2
(4) ANTIPERSPIRANTS & DEODORANTS:-

Anti perspirants:- Aluminium chlorhydrate used which has antibacterial and astringent
action. Aluminium chloride and Zirconium compounds are also used as antiperspirants.
Deodorants:--11 ( Hexachlorophene)
- TMTD (Tetra methyl triuram disulphide)
- Bithionol
- Bromosalicylanilide
- Diaphene
- Neomycin ( Antibiotic)
- Ion-exchange resin used like Amberlite
- Metal chelates like 1,3 Diketones used which chelate copper,
aluminium, Mg compounds.
 COSMETICS FOR HAIR:-

Includes following type of preparations:-
1. Shampoo
2. Hair tonics & Conditioners
3. Hair colorants and hair color remover
4. Hair grooming preparations
5. Depilatory & Epilatory
6. Shaving soaps & creams
7. Hair wave sets & lacquers ,rinses
1. SHAMPOO
Ideal characters of a shampoo:-
 Should effectively and completely remove the dust, excessive sebum.
 Should effectively wash hair.

 Should produce a good amount of foam
 The shampoo should be easily removed by rinsing with water.
 Should leave the hair non dry ,soft, lustrous with good, manageability.
 Should impart a pleasant fragrance to the hair,.
 Should not make the hand rough and chapped.
 Should not have any side effects or cause irritation to skin or eye.
Composition of shampoo:-
1) Principal surfactant (anionic type)
Non ionic surfactant has sufficient cleansing property but have low
foaming power. Cationic are toxic. So anionic are preferred.
2) Secondary surfactant (anionic or ampholytic detergent)
They modify detergent and surfactant properties of principal surfactant.
3) Antidandruff agents (selenium, cadmium sulfide, ZPTO)
4) Conditioning agent (lanolin, oil, herbal extract, egg, amino acids)
5) Pearlescent agents (substituted 4 methyl coumarins)
6) Sequestrants (EDTA)
Added because Ca, Mg salts are present in hard water. Soaps cause
dullness by deposition of Ca, Mg soaps on hair shaft. This prevented
by EDTA.
7) Thickening agents (alginates, PVA, MC)
8) Colors, perfumes and preservatives
Types of shampoo:-
1) Liquid cream shampoo
2) Solid cream and gel shampoo
3) Powder shampoo
4) Antidandruff shampoo
5) Aerosol foam shampoo
Formulation of shampoo:-
Liquid Cream shampoo Solid cream and Gel Shampoo

SLS 30% SLS………………………20%
PEG 400 Distearate Coconut monoethanolamide….1%
Mag. Stearate Propylene glycol monostearate..2%
Dist. Water Stearic acid…………………….5%
Ninol AB 21 Sodium hydroxide……………0.75%
Oleyl alcohol Water, perfume, Colour…….100
Perfume
PEG 400 distearate and Mg stearate

used to convert clear liquid shampoo
to liquid cream shampoo.
Ninol AB 21- Thickening agent
Oleyl alcohol- Conditioning agent
1) Powder shampoo 2) Antidandruff shampoo

Henna powder ………… 5 gm Selenium disulphide…… 2.5 gm
Borax …………………….15 gm Bentonite ......…………… 5 gm

Sod. carbonate ………… 25 gm Sod. Lauryl Sulphates ... 40 g
Pot. Carbonate ………….. 5 gm Water ………………… 52.5 gm
Soap powder…………….. 50 gm Perfume……………… q.s.
Perfume …………………. q.s.
Aerosol Shampoo:- SLS………………………………………….30%

Triethanolamine lauryl stearate…………..5%
Polyethylene glycol stearate………………3%
Perfume……………………………………..0.3%
Water…………………………………………100
90 parts of above packed with 2 parts of propellant 12 and 8 parts of propellant 14.
2) CONDITIONERS:- These are the preparations used after shampooing to render the hair
more lustrous, easy to comb, and free from static electricity when dry. Conditioners are
usually based on cationic detergents and fatty materials like lanolin, or mineral oil.
3) HAIR COLORANTS:-These are used either to hide gray hair or to change the color of the hair
.
An ideal hair dye should have following properties:-
 Should be nontoxic to the skin or hair, should not impair natural gloss and texture.
 Should not be a dermatitic sensitizer.
 The color imparted must be stable to air, light, water, shampoo.
 Should be easy to apply.
Hair dyes are divided into
1) Vegetable
Example is Henna
2) Metallic
Example:- Lead dyes, Bismuth dyes, Silver dyes, Copper, nickel, cobalt salts
Formula:- (Lead dyes)
Precipitated sulphur……………….1.3%
Lead acetate………………………..1.6%
Glycerine…………………………….9.6%
Rose water………………………….87.5%
3) Synthetic organic dyes
They are of two types.
a) Semipermanent dye. b) Permanent dyes
Thyoglycolic acid……50% Paraphenylene diamne dye
NH3 solution(PH 9.2)…100%
HAIR DYE REMOVER:-

Formula:- Formamidine sulfinic acid……………….1.5%
PVP…………………………………………5%
Ethylene glycol monobutyl ether………..5%
Ammonium carbonate……………………1%
Ammonia…………………………………..0.5%
CMC………………………………………..2.5%
Water up to ……………………………….1oo
Formamidine sulfinic acid is acting as hair dye remover.

4) HAIR GROOMING AIDS :-These are important group of cosmetics which are used both by
men and women to keep their hair in order for good looking, &enhance overall appearance.
Types:-
1. Brilliantines & Hair oils
2. Hair setting lotions
3. Hair creams
4. Hair lacquers or sprays
5) DEPILATORIES:-
• These are the preparations that remove superfluous hair by chemical breakdown. This
removes hair at the neck of the hair follicle and thus has advantage over razor shaver
which removes hair on a level with the surface of epidermis.
• Desirable Characters of an ideal depilatory preparation are:-
 Selective in action
 Efficient and rapid action in few minutes.
 Non toxic and non allergic to the skin.
 Odorless
 Easy to apply
 Stable
 Non staining
• INGREDIENTS :-
1. Inorganic sulphates (Sod,calcium,barium sulphide,Strontium sulphide)
2. Thioglycollates: - (Calcium.thioglycollate & Lithium thioglycollate)
3. Stannites: - sodium stannite
4. Enzymes:-Keratinase (3-4%)
5. Humectant: - Glycerol,Sorbitol ,Propylene glycol
FORMULATION
Name of ingredient Amount
1.Strontium sulphide 20.0 gm
2.Talc 20.0gm
3.Methyl cellulose 3.0 gm
4.Glycerin 15.0 gm
5.Water 42.0 gm
6.Perfume q.s
7. Preservative q.s
6) EPILATORIES:-
Epilation is longer lasting or even can be of permanent nature. This is achieved by plucking
the hair out and removing the root either by tweezers, threading,or by waxing.
• it is a permanent or long lasting effect (done by plucking the hair out, removing the
root)
• Camphor-impart cooling effect to reduce discomfort of hair pulling.
• Local Anaesthetics:- overcomes discomfort and pain
FORMULATION

Rosin 70 gm
Bees wax 20 gm
Ozokerite 10 gm
Perfume q.s
7) SHAVING PREPARATIONS: - These are preparations used to carryout shaving.

Types:-
a) Ued before shaving
b) Used after shaving
Preparations before shaving includes
1) Lather shaving creams
2) Brushless shaving cream
3) Shaving soaps (solid, cream)
4) Aerosol preparation
Aftershave lotion
SOAP BAR SOAP CREAM
I Ingredients A amount I Ingredients A Amount
Stearic acid 49 gm A. A. 䦋
Coconut oil 1 13 gm 1. Stearic acid 30 gm
Caustic potash 22 gm 2. Coconut oil 10 gm
Caustic soda 12 gm 3. Palm kernel oil 05 gm
Water 1.25 gm B. B.
Sodium dioxy
1. Pot. hydroxide
stStearate (50%) o.75 gm 07 gm
Sorbital liquid 1.25 gm 2. Sod. hydroxide 1.5 gm
Glycerol 0.75 gm 3. Water 36.5 gm
Perfume q.s 4. Perfume q.s
Preservative q.s 5. Preservative q.s
1) BRUSHLESS SHAVING CREAM –

Here Lathering with shaving brush is avoided.
Formulation of brushless shaving cream
INGREDIENTS AMOUNT
1. Stearic acid 16 gm
2. Mineral oil 14 gm
3. Spermaceti 2 gm
4. Glycerin 6 gm
5. Dil .ammonia solution 2 gm
6. Water 6 gm
7. Perfume q.s
8. Preservative q.s

2) LATHER SHAVING CREAM:-
Lathering with shaving brush is required.
INGREDIENTS A AMOUNT (%)
Stearic acid 28
Coconut oil 12
Palm oil 5
Pot. hydroxide 6.5
Sod. hydroxide 1.5
Glycerin 10
Perfume q.s
Preservative q.s
Water to make 100
AFTER SHAVE PREPARATION:-
Main purpose of shave preparation is to confer a pleasant feeling of comfort and well being
after shaving. This is achieved by giving slight coolness, anaesthesia, tautness or emolliency to
skin. At the same time it should be aseptic also.
Formula:-( Antiseptic after shave lotion)
Hyamine……………………………..0.25%
Alcohol……………………………….40%
Menthol………………………………0.005%
Benzocaine………………………….0.025%
Water…………………………………59.72%
Perfume………………………………q.s
 COSMETICS FOR NAILS:-

Includes
1. Nail polishes
2. Nail lacquers & removers
3. Nail bleaches & Stain removers
4. Cuticle remover & softener
5. Fingernail elongations
1 ) NAIL POLISHES:-
A distinction between nail polishes and lacquer is that in nail polish exert the abrasive
action. Due to friction it draw the blood to numerous capillaries of nail bed and increasing
blood supply, and exert stimulating effect to growth of nail. Examples are stannic oxide, talc,
precipitated chalk. Silica exert abrasive action.
Formula:- Stannic oxide………………………90%
Powdered silica…………………….8%
Butyl stearate………………………2%
Pigment & Perfume…………….. ..q.s
2) NAIL LACQUERS :-
• These are the preparations that cover the nail with a water and air impermeable layer
which normally remains for days.
• A good Nail lacquer should fulfill the following characters:-

1) Must be innocuous to the nail & the skin
2) Must be easy and inconvenient to apply
3) Product should be stable on storage
4) The product should produce a good &satisfactory film.
• COMPOSITION:-
1) Film former:-Nitro cellulose, Cellulose nitrate (mostly used), Cellulose acetate,

cellulose acetobutyrate, Ethyl. Cellulose.
2) Resins :- Give film more body, gloss, depth, adhesion
Natural - Gum damar, Benzoic acid, Gum copal, Shellac
Synthetic - Sulphonamide –Formaldehyde Resins
3) Solvents:-Mix of solvent is preferred, Mixing middle b.p solvents like alcohols,
acetates,and aromatic solvents rate of evaporation can be retarded.
4) Diluents:-
5) Plasticizers :- Dibutyl phthalate, Castor oil ,n-butyl stearate, castor oil
6) pearlescent material :-Guanine crystals
(R.I-1.8), mica flakes, Ti02, Platelets coated with bismuth oxychloride.
7) colors and perfumes
Formulation (Nail Lacquer)

INGREDIENT AMOUNT
Nitrocellulose 16 gm
Resin 9 gm
plasticizer 4.8 gm
Solvent 60.5 gm
Color 0.5 gm
Perfume q.s
b) LACQUER REMOVERS:-
These are also called as nail cleansers which is applied to remove nail lacquers.
FORMULATION OF LACQUER REMOVERS

Ingredients Amount
Butyl acetate 15 gm
Ethylene glycol monoethyl ether 80 gm
Propylene glycol ricinoleate 05 gm
Perfume q.s
c) CUTICLE REMOVERS AND SOFTENERS:-

Cuticle preparations either soften or remove the cuticles.
 COSMETICS FOR EYES:-

Includes following preparations
1. Eye shadow
2. Mascara

3. Eyebrow pencil
4. Eye cream
5. Eye liners
6. Kajal
1) EYE SHADOW:-
• Give a back ground of color to the eye
• Formulated as cream, liquid, powder or stick.
• Ultramarine(20 part)& Ti02 --- (BLUE)
• Iron oxide(30 part) &Ti02 (5 part)-- (BROWN)
Ingredients Amount
petroleum jelly 47.5 gm
Liquid lanolin 4.5 gm
Bees wax 4.5 gm
Micro crystalline wax 8.5 gm
Isopropyl myristate 35 gm
2) EYE LINER:-
Types
1) Pencil type
2) Liquid type (suspension in a base containing film forming material)
3) Cake eye liners
Formulation of Cake type eyeliner

Kaolin 5%
Zn Stearate 12%
Ppted Caco3 7%
Pigment 10%
Talc to make 100 %
3) EYE BROW PENCIL:-

• Contain high proportion of wax to increase M.P so that these can be moulded into
sticks.
Ingredient Amount
Bees wax 25%
Ozokerite 25%
Butyl stearate 8%
Lanolin 2%
Castor oil 25%
Mineral oil 15%
Perfume q.s
Antioxidant q.s
4) MASCARA:-
• Black pigmented preparation for applying to eye lashes or eye brows ,it darkens the
eye lashes & gives an illusion of their density and length.
• Type:- Cake , Cream , Liquid
Formulation:-
Carbon black 55 %
Coconut oil sodium soap 25%
Palm oil –sodium soap 22.5%
7) QUALITY CONTROL OF COSMETICS :-

We all know that “Price of a product is quickly forgotten but the quality is remembered” so
quality control plays a vital role regarding monitoring different parameters that may affect
quality &also helps in producing quality product every time.
Includes :-
1) RAW MATERIAL CONTROL
2) INTERMEDIATE PRODUCT CONTROL
3) FINISHED PRODUCT CONTROL
4) PACKAGING MATERIAL CONTROL
1) Q.C OF RAW MATERIAL:-

• Done by determination of Bioburden
The bacterias that are monitored in raw materials include:-
• Enterobacteriaceae
• E.Coli
• Salmonella
• Pseudomonas aeruginosa
• Staphylococcus aureus
2) Q.C OF INTERMEDIATES AND BULK FINISHED PRODUCT:-

Basing on the type of product few typical processing parameters are continuously to
ensure quality final product. few of them have been enlisted here.
a) CREAMS & LOTIONS:-
 Mechanics,
 perfume addition temp
 addition of phases
 Viscosity
 Temp of filling
 rate of cooling
b) FACE POWDER
 Uniformity of mixing
 Apparent density
 Shade ,color

 Compression pressure (compacts)
c) LIPSTICKS
 Color match
 Texture
 Softening point
 Breaking point test
d) SHAMPOO:-
 -Foam & foam stability
 -Detergency & coloring action
 -Wetting action
 -Eye irritation
 -Oral toxicity
e) NAIL LACQUER:-
 Color match, Drying rate,
 Non volatile content,
 Smoothness,
 Gloss, Hardness, abrasion resistance, adhesion etc.
Sampling size for final Q.C:-
No of packaging No of packing selected
Up to 3 Each
4-50 03
51-150 04
151-300 05
301-500 06
>500 07
8) COSMOCEUTICALS: - These are cosmetics with therapeutic & disease fighting property
The following substances are now recognized having cosmoceutical potentials

1) Polysacharides :-Fom Tamarind extract and skin beneficial acids from Coriander
extract provide moisture-lipid balance preventing dryness and itching 2
2) Wheat Germ Oil guard skin against free radical damage.
3) Moringa Extract protects your skin against dust and harmful pollutants.

4) Galanga Oil * protects skin from harmful UV rays and fights pimple in acne prone skin.
Skin beneficial fatty acids from Coriander boost the deposition of skin proteins,
enhancing tissue repair
5) Cococin provides wholesome freshness and nourishment of natural tender coconut
water. Natural growth promoters like kinetin and amino acids in Cococin® impart
natural conditioning, suppleness and glow to the skin.
6) Ubiquinone(CO.Q.10) rejuvenates and increases the oxygen uptake into the cells.
7) Tetrahydrocurcuminoids, patented molecule from turmeric in combination with
potent antioxidants - Alpha lipolic acid and Ubiquinone reduces fine lines, wrinkles,
crow's feet, minimizes the UV induced signs of photo aging and pigmentation, leaving
behind blemish-free, youthful skin.
8) Isoflavons from Soy impart luster and brightness to the skin by improving skin
thickness, skin blood circulation, increased desquamation resulting in excellent surface
texture and softness.
9) Tetrahydropiperine as Cosmoperine from Pepper improves the dermal penetration of
the actives,
MISCELLANEOUS ISSUES:-
SKIN TESTING:-
Type of cosmetic Preparation Suspected agent to cause harm
CREAMS Mercurial & Salicylic acid

DEODORANT Phenolic antimicrobials, Aluminium.chloride
DEPILATORIES Sulphides of alkali (R.A)
HAIR DYE Ammonia solution
COLD WAVE LOTIONS Thioglycollates
LIPSTICK Bromofluorescein dye (cause Cheilitis)
HAIR & BATH Prep Agent which cause eye irritation
4) TEN SYNTHETIC COSMETIC INGREDIENTS TO AVOID:-

Organic consumers association has given the following list of chemicals that are to
be avoided in preparation of cosmetics.
1. Imidazolidinyl Urea and Diazolidinyl Urea
2. Methyl and Propyl and Butyl and Ethyl Paraben
3. Petrolatum
4. Propylene Glycol
5. PVP/VA Copolymer
6. Sodium Lauryl Sulfate
7. Stearalkonium Chloride
8. Synthetic Colors
Example: FD&C Red No. 6 / D&C Green No. 6
9. Synthetic Fragrances
10. Triethanolamine
Newer approaches

 Hair Growth-accelerating preparation containing chlorogenic acid or its isomer for
treating androgenic alopecia and its formulation.
 Cosmetic composition contain in caffeine, acetic acid and sodium hyaluronate for
preventing alopecia.
DENTAL PRODUCTS
LIST OF CONTENTS
1) Introduction
2) The teeth and common problem
3) Causes of oral health problems
4) Classification
5) Formulation of dentifrices
6) Type of dentifrices
1. Tooth pastes
2. Tooth powders
3. Solid blocks
4. Liquid preparations
5. Mouth wash
7) Topical anesthetics
8) Tartar reducing product
9) Mechanical method for plaque control
10) Safety
11) Dental care product
12) Newer approaches
INTRODUCTION
Dentifrice a preparation for cleansing and polishing the teeth; it may contain a therapeutic
agent, such as fluoride, to inhibit dental caries.
A substance, such as a paste or powder, for cleaning the teeth.

Etymology: L, dens + fricare, to rub
a pharmaceutic compound used with a toothbrush for cleaning and polishing the teeth. It
typically contains a mild abrasive, detergent, flavoring agent, fluoride, and binder. Other
common ingredients are deodorants, humectants, desensitizers, and various medications to
prevent dental caries. Also called toothpaste.
Dentifrice (toothpaste)
A pharmaceutical compound used in conjunction with the toothbrush to clean and polish the
teeth. Contains a mild abrasive, a detergent, a flavoring agent, a binder, and occasionally
deodorants and various medicaments designed as caries preventives (e.g., antiseptics).
Two type of Dentifrice

1. Simple cleansing dentifrices
2. Therapeutics dentifrices: Therapeutic dentifrices may contain the bactericidal,
bacteriostatic, enzyme inhibiting or acid neutralizing qualities of the drugs or chemicals.
The teeth and common problem

1. Bad Breath
If you suffer from bad breath, you are not alone. Bad breath, also called halitosis, can be
downright embarrassing. According to dental studies, about 85% of people with persistent
bad breath have a dental condition that is to blame. Gum disease, cavities, oral cancer, dry
mouth and bacteria on the tongue are some of the dental problems that can cause bad
breath. Using mouthwash to cover up bad breath when a dental problem is present will only
mask the odor and not cure it. If you suffer from chronic bad breath, visit your dentist to rule
out any of these problems.
2. Tooth Decay
Did you know tooth decay, also known as cavities, is the second most prevalent disease in the
United States (the common cold is first). Tooth decay occurs when plague, the sticky
substance that forms on teeth, combines with the sugars and / or starches of the food we eat.
This combination produces acids that attack tooth enamel. The best way to prevent tooth
decay is by brushing twice a day, flossing daily and going to your regular dental check ups.
Eating healthy foods and avoiding snacks and drinks that are high in sugar are also ways to
prevent decay.
3. Gum (Periodontal) Disease

Studies have shown that periodontal disease, also known as gum disease, is linked to heart
attacks and strokes. Gum disease is an infection in the gums surrounding the teeth. Gum
disease is also one of the main causes of tooth loss among adults. There are two major stages
of gum disease: gingivitis and periodontitis. Regular dental check ups along with brushing at
least twice a day and flossing daily play an important role in preventing gum disease.
4. Oral Cancer
Oral cancer is a serious and deadly disease that affects millions of people. In fact, the Oral
Cancer Foundation estimates that someone in the United States dies every hour of every day
from oral cancer. Over 300,000 new cases of oral cancer are diagnosed every year, worldwide.
This serious dental disease, which pertains to the mouth, lips or throat, is often highly curable
if diagnosed and treated in the early stages.
5. Mouth Sores
There are several different types of mouth sores and they can be pesky and bothersome.
Unless a mouth sore lasts more than two weeks, it is usually nothing to worry about and will
disappear on its own. Common mouth sores are canker sores, fever blisters, cold sores, ulcers
and thrush.
6. Tooth Erosion
Tooth erosion is the loss of tooth structure and is caused by acid attacking the enamel. Tooth
erosion signs and symptoms can range from sensitivity to more severe problems such as
cracking. Tooth erosion is more common than people might think, but it can also be easily
prevented.
7. Tooth Sensitivity
Tooth sensitivity is a common problem that affects millions of people. Basically, tooth
sensitivity means experiencing pain or discomfort to your teeth from sweets, cold air, hot
drinks, cold drinks or ice cream. Some people with sensitive teeth even experience discomfort
from brushing and flossing. The good news is that sensitive teeth can be treated.

8. Toothaches and Dental Emergencies
I can't think of much worse than suffering from a toothache. While many toothaches and
dental emergencies can be easily avoided just by regular visits to the dentist, we all know that
accidents can and do happen. Having a dental emergency can be very painful and scary.
Fortunately, you can do several things until you are able to see your dentist.
9. Unattractive Smile
While an unattractive smile is not technically a "dental problem," it is considered a dental
problem by people who are unhappy with their smile and it's also a major reason that many
patients seek dental treatment. An unattractive smile can really lower a person's self-esteem.
Luckily, with today's technologies and developments, anyone can have a beautiful smile.
Whether it's teeth whitening, dental implants, orthodontics or other cosmetic dental work,
chances are that your dentist can give you the smile of your dreams.
Causes of oral health problems
1)Pellicle
The pellicle is rapidly formed on all freshly cleaned tooth surfaces by the deposition and
absorption of some salivary proteins. It is less than 0.1 mm thick and is invisible to the naked
eye.
2)Plaque
Following the deposition of pellicle on a freshly cleaned tooth surface, plaque forms rapidly.
Plaque is an invisible sticky film of bacteria, salivary proteins, and polysaccharides that
accumulates on everyone's teeth. It is not washed away by the saliva, and the composition of
bacteria depends upon the host, the site in the mouth and the age of the plaque layer. In the
event of poor oral hygiene, plaque ages and there is a shift in bacterial population to more
harmful organisms as the plaque age.
3)Dental calculus (tartar)

Dental plaque may itself become mineralized and this hard deposit is called calculus. It
accumulates on the tooth surface mainly at the gingival margin opposite the salivary ducts. It
is a hard mineral deposit, containing predominantly calcium and phosphate, very tightly
bound to the tooth surface. Once it has formed, it is virtually impossible to remove it except
by a dental hygienist.
CLASSIFICATION OF DENTAL PRODUCTS
Classification depending on Dental Problems.

I. Products for carries control.
a. Systemic fluoride
b. Topical fluoride
i. Dentifrices
ii. Gel
iii. Rinses
iv. Miscellaneous
II. Products for plaque control.
a. Chemical agents
i. Dentifrices
ii. Mouth washes
b. Mechanical products
i. Tooth brushes
ii. Dental floss
iii. Other aids to plaque removal.
III. Products for tooth surface hypersensitivity.
IV. Topical anesthetic.
V. Halitosis
TOOTHPASTE INGREDIENTS AND MANUFACTURE
Requirements of a toothpaste/dentifrice
The major requirements of oral preparations, especially toothpastes, have been summarized
on many occasions in the past. For a toothpaste, these requirements were:
1. When used properly, with an efficient toothbrush, it should clean the teeth adequately,
that is, remove food debris, plaque and stains.
2. It should leave the mouth with a fresh, clean sensation.
3. Its cost should be such as to encourage regular and frequent use by all.
4. It should be harmless, pleasant and convenient to use. (It should conform to the EC
Cosmetics Directive in that it is 'not liable to cause damage to human health when applied
under normal usage conditions'.)
5. It should be capable of being packed economically and should be stable in storage during its
commercial shelf-life.
6. It should conform to accepted standards in terms of its abrasivity to enamel and dentine.
7. Claims should be substantiated by properly conducted clinical trials.
These requirements remain valid today, with perhaps only the priority and emphasis placed
on any individual point being changed.
To achieve this it is necessary to have a high solid suspension in a stable viscous form and
therefore gelling agents or thickening polymers have to be incorporated.
To prevent it from drying out it also becomes necessary to add humectants to the system.
Finally, colours (if desired), and preservatives (if necessary), are also added, creating a
complex matrix of ingredients which can be classified as a 'simple' cosmetic toothpaste,
i.e. 1. Cleaning and polishing agents (abrasives).
2. Surfactant (cleaning and foaming).
3. Humectants.
4. Binding (gelling) agents.
5. Sweetener.
6. Flavouring agents.
7. Minor ingredients (colours, whitening agents, preservatives).
In such a complex system many interactions can take place depending upon internal and
external factors. Even the 'simple' formulations require extensive stability testing, over a
range of temperatures and time, in order to be confident that the product quality does
not change upon storage. Only in this way can the manufacturer have a high degree of
confidence that the product seen by the consumer is of premium quality.
'A dentifrice should be no more abrasive than is necessary to keep the teeth clean - that is
free of accessible plaque, debris and superficial stain'. Thus, considerable performance testing
on the final formulation is necessary.
 Ingredients used in toothpastes
All ingredients generally have specifications approved for use in foodstuffs or are
special grades available for dental preparations, especially abrasives.
1. Cleaning and polishing agents (abrasives)
Clearly the main purpose of the cleaning and polishing agent is to remove any adherent layer
on the teeth, and the materials normally considered are given below.
(a) Dental grade silicas (SiO2)n.
In a relatively short period of time silica has generally become the abrasive of choice
because it offers great flexibility to the formulator.
It can be produced to a high state of purity giving excellent compatibility with therapeutic
additives and flavours.
Varying the particle size can alter the finished product abrasivity.
Clear gels can be formulated by carefully matching the refractive indices of silica used with
the liquid phase of the toothpaste.
Silica can also give additional thickening properties to the dental cream if extremely fine
particle sizes are used (silica thickeners).
When used in toothpastes, silica is generally incorporated at levels between 10 and 30%.
(b) Dicalcium phosphate dihydrate (DCPD) CaHPO4-2H2O.
DCPD is one of the most commonly used dental cream abrasives, perhaps because it gives
good flavour stability.
It is normally white in colour and gives toothpaste which generally does not require
additional whitening agents.
The main drawback is that it is only fully compatible with sodium monofluorophosphate as
the fluoride source because of the presence of free calcium ions. Formulating with other
therapeutic fluoride sources does not appear to have been successful.
The abrasive is usually formulated at levels between 40% and 50% to give relatively dense
toothpaste.
(c) Calcium carbonate CaCO3.
Calcium carbonate is probably one of the most commonly used dental cream abrasives.
Precipitated calcium carbonate (chalk) is available with a white or off-white colour and
both particle size and crystalline form can be varied, depending upon its conditions of
manufacture.
As a result of its structure and calcium content, precipitated calcium carbonate is
incompatible with sodium fluoride, but is stable with the less reactive sodium
monofluorophosphate.
Calcium carbonate is also used at levels between 30% and 50% to give a relatively dense
paste.
(d) Sodium bicarbonate (or baking soda NaHCO3).
Sodium bicarbonate has a unique 'salty' mouth-feel that tends to polarize consumers,
many finding it attractive possibly due to its heritage as a cleaner/deodorizer.
It is a very mild abrasive, usually used at a 5-30% level, in combination with other
abrasives such as silica or calcium carbonate to achieve the required cleaning action.
(e) Hydrated alumina Al2O3 • 3H2O or Al(OH)3.
Hydrated alumina is relatively inert, cost-effective, and available as a white amorphous
solid.
It has good compatibility with sodium monofluorophosphate and other ingredients
added to give a therapeutic benefit.
The abrasive is usually formulated at levels between 40% and 50% to give a relatively
dense paste.
(f) Other abrasives.
Insoluble sodium metaphosphate (IMP) (NaPO3)x, is available as a free-flowing white
powder, with moderate abrasivity and good compatibility with flavour oils, sodium
monofluorophosphate and ionic fluoride sources (stannous and sodium fluorides).
it is now only used in extremely limited amounts.
Calcium pyrophosphate (CPP), Ca2P2O7, was the original abrasive purposely
developed for its compatibility with stannous fluoride to give the first commercially
available therapeutic dentifrice containing fluoride.
2. Surfactants
Surfactants are used in the toothpaste to aid in the penetration of the surface film on
the tooth by lowering the surface tension.
They also provide the secondary benefits of providing foam to suspend and remove
the debris, and the subjective perception of toothpaste performance.
They often have better foaming properties, and are more compatible with other
ingredients since their pH range is essentially neutral.
They are also available with a higher degree of purity that can eliminate some of the
bitter flavour components that affect taste.
In general, surfactants are used at a concentration of around 1-2% by weight in the
dental cream.
(a) Sodium lauryl sulphate (SLS)

This has been the main surfactant of choice, used in nearly all toothpaste brands.
However, while alternative surfactants have been considered, and will continue
to be looked at and developed, none is in widespread use since all have some
disadvantages compared to SLS.
3. Humectants
Humectants are used to prevent the paste from drying out and hardening to an
unacceptable level.
At the same time they give shine and some plasticity to the paste.
Generally only two major humectants are considered for use in toothpaste, often in
combination with small amounts of additional minor humectants.
(a) Glycerin, CH2OHCHOHCH2OH.

Glycerin is still the humectant used in greatest bulk quantity in toothpaste. It is one of
the best humectants, producing a shiny, glossy product.
It is stable, non-toxic, available from both synthetic and natural sources, and provides
a useful sweetening function to the paste.
(b) Sorbitol, CH2OH(CHOH)4CH2OH.

Sorbitol syrup (approximately 70%) is also extensively used throughout the industry
and is sometimes considered superior to glycerin depending upon the formulation.
It also imparts sweetness, and is a stable humectant.
(c) Propylene Glycol, CH3CHOHCH2OH and Polyethylene Glycol, CH2OH(CHOH)nCH2OH.

Propylene glycol and polyethylene glycol are not normally used as the sole humectant
in a paste since they are more expensive and, in the case of propylene glycol, can
impart a slightly bitter taste.

They are more generally used in relatively small amounts in combination with either
glycerin or sorbitol.
The amount of humectant in any formula obviously has to be adjusted depending
upon the other constituents of the formula (especially abrasive nature), but generally
the total humectant loading is in the range 10-30% by weight.
(d) Xylitol (CH2OH(CHOH)3CH2OH).

Xylitol is a polyol equivalent of sorbitol, but with a five-carbon chain instead of six.
Like sorbitol it is a naturally occurring material with a relative sweetness equal to
sugar.
Currently its high cost and limited availability restrict its use.
4. Gelling agents
Gelling or binding agents are hydrophilic (water-loving) colloids which disperse and
swell in the water phase of the toothpaste and are necessary to maintain the
integral stability of the paste and prevent separation into component phases.
They are probably the most widely variable components of toothpaste and the
choice of gelling agent can greatly influence the dispersibility of the paste in the
mouth, the generation of foam and, above all, the release of the flavor
components.
Some formulations have combinations of gelling agents in order to ahieve the desired
consumer preferences.
(a) Sodium Carboxymethyl Cellulose CMC.
Carboxymethyl cellulose is one of the preferred gelling agents for use in toothpaste.
It can be manufactured to a high state of purity, and tailor-made for an individual
requirement by varying the degree of substitution on the cellulose chain.
This can give flexibility in terms of solubility, elasticity and some increased stability in
the presence of electrolytes.
(b) Carrageenan.
It is a purified colloid, consisting of a mixture of sulfated polysaccharides and, as with
all natural products, it can be of variable quality, which could cause a problem for any
formulator.
Therefore, it is standardized either by repeated blending, or dilution with variable
amounts of inert material.
Some flexibility in the gelling properties of carrageenan can be achieved by controlling
the cations present by ion exchange.
(c) Miscellaneous gelling agents

Xanthan - This is a polysaccharide produced by fermentation technology. It offers excellent
properties for use in toothpaste since it gives a highly structured gel, relatively easily broken
down when sheared, but which recovers rapidly. It is relatively insensitive to electrolytes and
heat, but unfortunately it is generally incompatible with cellulosic materials because of
contaminating enzymes that degrade cellulose.
Hydroxy ethyl cellulose HEC - This is occasionally used as an alternative to carboxymethyl

cellulose (CMC), especially when a greater electrolyte tolerance is required.

Synthetic polymers – Cross linked acrylic acid polymers have become more intensively used in
the past decade because of their useful thickening and suspending properties combined with
their inertness and their stability to heat and ageing.
Clays - Colloidal clays, either natural processed bentonites or synthetic clays,have been used
as binding agents because of their thixotropic properties. Depending upon the rest of the
formula components (e.g. abrasive, amount of free water), the level of gelling agent added to
a paste can vary from 0.5% to 2.0% by weight.
5. Sweetening agents
These are important for product acceptance, since the final product must be neither
too sweet nor too bitter.
These ingredients must always be considered in partnership with the flavour because
of their combined impact.
(a) Sodium saccharin.

This is the sweetening agent in widest commercial use, and is generally used at a level
between 0.05% and 0.5% by weight.
6. Flavours
Flavours are probably the most crucial part of toothpaste because of consumer
preferences.
The flavour is a blend of many suitable oils, with peppermint and spearmint being the
major base components. These are nearly always fortified with other components
such as thymol, anethole, menthol (to give a pleasant cooling effect), eugenol (clove
oil), cinnamon, eucalyptol, aniseed, and wintergreen (to give a medicinal effect).
In addition, because the flavour is a mixture of sparingly soluble organic oils, its
interactions with the other dentifrice components are often unpredictable and
unexpected.
Taste and stability can be influenced greatly by both the other components of the
dental cream, e.g. free water content, or absorption by the abrasive (perhaps to the
surface), and also by the physical properties of the dental cream, e.g. pH, viscosity etc.,
Depending upon the formulation, e.g. the abrasive nature and level, the gelling agent
used and the presence of therapeutic ingredients which may impact taste perception,
the flavour level may vary from around 0.5% to 1.5% by weight.
7. Minor ingredients
(a) Titanium Dioxide TiO2- Titanium dioxide may be added to give additional whiteness and
brilliance to the paste.
(b) Colours. Colours can be an integral part of the aspect of any toothpaste that may influence
consumer preference and purchase intent. The EEC Cosmetics Directive (Annex IV) lists the
permitted colours and only a small amount is necessary to create a large impact, <0.01% by
weight.
(c) pH regulators. Occasionally buffering systems need to be added to the dental cream to
adjust the pH of the final finished product.

(d) Sparkles. A recent introduction in the marketplace is the addition of small reflective mica
particles to coloured transparent gel products. This gives toothpaste the appearance of
containing 'sparkles' and is especially aimed at younger children.
8. Fluoride and other 'active' ingredients

The earliest fluoride dentifrices contained sodium fluoride.
However, the fluoride was biologically unavailable because the calcium in the
dentifrice abrasive bound the fluoride and thus inactivated it.
Although a number of dentifrices containing fluoride are on the market, not all provide
available fluoride because the abrasive systems that some dentifrices contain
inactivate the fluoride.
Therefore, the product may contain as much fluoride as any other dentifrice but it is
not available.
Also, if the product has a short shelf life, it will be ineffective if poor marketing gets it
to the consumer too late.
For these reasons, only dentifrices approved by the Council on Scientific Affairs of the
American Dental.
Various topical fluoride preparations are available as given in the table.

Form of fluoride Preparations Concentration of fluoride
Topical solution 1.23 % in 1 % phosphoric acid
Acidulated phosphate Topical gel 1.23 % in 1 % phosphoric acid
fluoride Mouth rinse 0.02-0.04 %
Paste 1.2 %
Dentifrices 1.6 %
Amine fluoride
Mouth rinse 2.5 %
Topical solution 2%
Sodium fluoride Mouth rinse 2.5 %
Dentifrice 0.2 % (weekly)
Sodium 0.76 – 0.8 %
Dentifrices
monofuorophosphate
Topical solution 8%
Mouth rinse 0.1 %
Stannous fluoride Paste 8%
Gel 0.4 %
Dentifrices 0.4 %
Currently accepted dentifrices contain sodium monofluorophosphate,sodium fluoride, or, less

frequently,stannous fluoride, all of which reduce caries by approximately
25% when used daily.
The composition of some popular tooth pastes is given in table.

Foaming
Brand Fluoride Abrasive Sweetener
agent
10 % Hydrated
silica xerogel 1.5 %
Aim 0.8 % Na.MFP 67 % sorbitol
19 % Hydrated SLS
silica
Aim extra 1.2 % Na.MFP

strength
12.6 % calcium
Aqua fresh 0.76 % Na.MFP carbonate 52.8 % sorbitol 1.15 % SLS
12 % silica
48.76 % dicalcium 1.2 %
Colgate 0.76 % Na.MFP 22 % glycerin
phosphate SLS
Stannous fluoride
 Dentifrices stained teeth, particularly in pits and fissures.
 This stain is related to the tin in this compound, which adheres to plaque.
 The significance of this staining and its esthetic problems have resulted in a decreased
usage in dentifrices.
 Stannous fluoride dentifrices are marketed in a plastic container because a reaction of
stannous ions at an acid pH occurs when conventional soft metal tubes are used.
 Dentifrices containing stannous fluoride as an active ingredient are no longer widely
marketed; however, these formulations were the first to be evaluated for caries-
reducing properties.
 Effectiveness in caries reduction varied from 23 to 34%.
Amine fluoride
 Amine fluorides also have strong plaque-reducing properties.
 However, although the amine fluorides may be more effective for caries reduction
than other forms of fluoride, the FDA has not allowed these products to be extensively
tested in this country.
Sodium fluoride
 Recent studies of sodium fluoride dentifrices formulated to ensure ready availability of
fluoride ions have shown anticaries benefits similar to those obtained in clinical caries
trials with dentifrices containing stannous fluoride and sodium monofluorophosphate.
 Clinical caries trials conducted under well controlled, daily supervised brushing
conditions have reported reductions in dental caries of approximately 25–48%.
Sodium monofluorophosphate
 A number of clinical studies have been conducted with dentifrices containing 0.76%
monofluorophosphate (MFP).
 The data from these controlled clinical studies of sodium MFP dentifrices have
indicated reductions in dental caries ranging from approximately 17–42%.
Therapeutic effects of fluoride

Caries control
M/A: fluoride ion can replace the hydroxyl ion in hydroxyapatite the major crystalline
structure of enamel.
 The substituted crystals called fluorapatite is more resistant to acid, such as those
produced by plaque bacteria.
 As fluoride is also an antienzyme. It may inhibit enzymatic acid production by plaque
bacteria.
Dental plaque control

 Mainly stannous fluoride is used for this purpose.
M/A: related to an alteration of bacterial aggregation and metabolism.
Caries sites
1. Pit-and-fissure caries develop initially in the fissures of the teeth, but can spread into
the dentine
2. Smooth-surface caries are most common on interdental surfaces, but can occur on
any smooth surface of the tooth
3. Root caries attack the cementum and dentine, which becomes exposed as gums
recede
Sources of fluoride
 Topical agents
 Fluoridated water
 Other ingested source
 Fluoride effect on remineralization and demineralization of ename

Promote remineralization1
Reduce demineralization Inhibit acid generation

from plaque bacteria4
MECHANICAL PRODUCTS FOR PLAQUE CONTROL
 Toothbrush
 Toothpaste
 Dental Floss

 Tongue Scraper
1. Toothbrush
The toothbrush is the primary dental hygiene product you need to take care of your teeth.
First, the regular toothbrush alone provides a plethora of options. Toothbrushes come in
various sizes and styles. Various brushes differ from the handle to the bristles. That’s why
buying a toothbrush can be a confusing task.
In choosing a brush, most dentists recommend soft-bristled brushes more because these can
best remove plaque and traces of food that gets stuck in the teeth. You should also choose a
brush that does not have a big head. Small-headed brushes can reach the back areas of the
mouth for thorough and complete mouth cleaning. You can also choose from squared heads
or tapered ones.
As for the handle, you should go for brushes that provide good grip. The shape of the handles
themselves differs a lot. But the most important part of the brush is the bristles. There are
many forms of bristles, such as rippled, flat, trimmed, or domed ones. All these different types
of bristles provide specific benefits that may help meet your needs.
Aside from regular brushes, however, you can also use power brushes, which is very popular
among younger users. These powered brushes help clean the teeth better than children
usually can.
2. Toothpaste
Another important choice you have to make is what toothpaste to use to go with that perfect
brush. The toothpaste aisle in the supermarket is highly congested, and the different brands
and kinds often differ in ways that are vague to consumers. That’s why it is even harder to
choose toothpaste than a toothbrush. The trick, however, is to follow the fluoride arrow. Look
for toothpaste that contains fluoride, and the brand usually doesn’t matter much. Fluoride is
an essential ingredient that can provide strengthening for your teeth. Fluoride works by
keeping cavities away and also by polishing tooth enamel.
Another clue to look for is the seal of approval by the American Dental Association, which will
help lead you to safe and effective products that have passed clinical scrutiny. You can also
consider your specific tastes, such as desensitizing toothpaste for sensitive teeth, whitening
toothpaste for yellowing teeth, and tar-tar control toothpaste for those dealing with tar-tar
problems.
3. Dental Floss
Another important dental hygiene product is dental floss, which is often neglected by a lot of
people. Flossing should be done at least once daily, and benefits are far ranging. Flossing can
help clean teeth and in between teeth to make sure no food debris are left. It can help you
easily get rid of the food stuck irritatingly between your teeth, which can lead to tooth decay,
gum disease, and accumulation of bacteria in the long run. Also, bacteria can lead to bad
breath, so dental floss can help keep bad breath away.
4. Tongue Scraper
Another less popular product is the tongue scraper or tongue cleaner, which cleans the
surface of the tongue to remove bacteria, food debris, fungi, and dead cells. The tongue is
vulnerable to bacteria and fungi that can cause bad breath, oral problems and even medical
conditions. Tongue cleaners come in a general form, but one thing to note is that it should be

used before brushing your teeth, since brushing might cause the stuff on your tongue to
recede into the throat.
Tartar (Calculus)-Reducing Products
 A number of products, both dentifrices and mouthrinses,are available for reduction of

supragingival calculus (tartar) in dental patients. Calculus reduction has been shown with
dentifrices containing pyrophosphates, zinc salts, triclosan, and papain.
 The incidence of calculus formation ranges from 45 to 66%, with some variation between
males and females and different age groups. Although supragingival calculus is not a major
etiologic agent for gingivitis or periodontitis, its surface porosity provides an environment
for plaque formation.
 In addition, it serves as a plaque-delivery system by holding plaque against gingival tissues.
Although plaque formation has been well correlated with gingivitis and periodontitis, a
similar correlation for calculus has not been reported.
 For this reason, the ADA does not offer an acceptance program for products that reduce
calculus formation because this is considered to be a cosmetic issue, rather than an issue
of disease.
 The mechanism of action of the calculus-reducing chemicals is related to the latter’s ability
to inhibit crystal growth and interrupt the transformation of calcium phosphate (found in
foods and saliva) into dental calculus.
This effect may occur as follows:
1. The agents complex on the tooth surface to block receptor sites for calcium phosphate that
precipitates from saliva and chemically absorbs to initiate calculus formation.
2. This same receptor site blockage also occurs in the calculus matrix as it begins to form.
3. The pyrophosphate complexes combine with free calcium in saliva to inhibit the
attachment at the tooth surface (probably a secondary mechanism).
TYPE OF DENTIFRICES
(A) Pastes form – Tooth paste
(B) Powder form – Tooth powder
(C) Solid blocks
(D) liquids
(A) TOOTH PASTES

Tooth pastes are most popular valuable and widely used preparations for cleansing the
teeth. It has largest share of dental cleansing and care preparations.
Tooth pastes are preferred over other dental preparations because of following reasons.
Easy to take and spread on the tooth brush
No spillage or wastage
Attractive consistency
Proper distribution in mouth
Available in wide varieties
A good tooth paste should have following characteristics

It must clean the dental surface properly without any scratches.

Consistency should be such that it can be easily squeezed out of the tube to spread on
the brush, but should not penetrate in to the brush.
The consistency should remain constant in wide range of temperature during shelf life.
It should be non toxic and should not sensitize buccal membrane.
It should not interact with the container material.
It should have pleasant taste and odour.
It should have good appearance.
Formulation:
Method: - 1
The binder, prewetted with the humectant, it is disperse in liquid portion containing
the saccharin and preservative and allow swelling to form a homogeneous gel. The swelling
may be accelerated by heat and agitation. The solid abrasive is added slowly to homogeneous
gel and mixed in mixer until a paste formed. The flavour and detergent are added last and
distributed uniformly.
Excessive, aeration, particularly in the presence of detergent, should be avoided. The
paste can then be milled, deairated and tubed.
Method: - 2
The binder is premixed with solid abrasive, which is then mixed with the liquid phase,
containing humectant, preservative and sweetener into a mixer. After formation of
homogeneous paste, the flavour and detergent are added, mixed, milled deairated and tubed.
(A) TOOTH POWDERS

Tooth powders are oldest and simplest preparations. Over the years their market
share has been reduced due to popularity of pastes, but steel they have a considerable
market share.
The main problems encountered with powders are-
Floating of powder in air during manufacturing.
Formation of cake on storage
Uneven distribution in mouth
Composition
Tooth powders contain the following ingredients-
 Abrasives
 Surfactants or detergents
 Sweetening agents
 Flavours
 Colours
Abrasives are used in manufacturing of tooth powders are similar to that of tooth pastes.
Though lighter calcium carbonate is used in tooth paste but in tooth powders heavier grade
calcium carbonate is used.
Other ingredients are similar to that of tooth paste.
General procedure for manufacture

This is done by simple mixing
First ingredients of small quantity are premixed and then mixed with other
ingredients.
Ribbon type or agitator type of mixer are used.
Flavour can be sprayed on to the bulk or can be premixed with part of some abrasive.

(3) SOLID BLOCKS
Solid dentifrice is like a soap preparation.
Basically they consist of tooth powder suspended in a base of soap powder,
water, and humectant.
Solid detifrices provide a convenient and handy from of cleaning for the teeth.
Formulation
The soap first dissolved in a mixture of glycerin and water with the aid of heat. The
powder (abrasive) is then mixed until soft mass formed. Mass is dried on trays, cut into
blocks.
EVALUATION OF SOLID DENTAL PRODUCTS

Identification of ingredients and estimation of their contents are essential components
of overall quality control and evaluation of dental care products. The products, tooth pastes
and tooth powders, can be basically classified into foam forming and non-foam forming.
Some other special evaluation tests are as follows:
Abrasiveness
Various tests have been designed and reported over the year, mostly on the set of extracted
teeth. The teeth were mechanically brushed with pastes or powders and then the effects
were studied by observation, mechanical or other means. Abrasive character normally
depended on the particle size. So, study of particle size can also give such idea.
Particle size
This can be determined by microscopic study of the particles or by sieving or other means.
Cleansing property
This is studied by measuring the change in the reflectance character of a lacquer coating on
the polyester film caused by brushing with a tooth cleanser (paste or powder). Also an in vivo
test has been suggested in which teeth were brushed for two weeks and condition of teeth
was assessed before and after use with the help of photo graphs.
Consistency
It is important that the product , paste, should maintain the consistency to enable the product
press out from the container. Study of viscosity is essential for this. Rheology of powders is
also important for proper flow of the powder from the container.
pH of the product
pH of the dispersion of 10 % of the product in water is determined by PH meter.
Foaming character
This test is specially required for foam forming tooth pastes or tooth powders. Specific
amount of product can be mixed with specific amount of water and to be shaken. The foam
thus formed is studied for its nature, stability, washability.
Limit test for arsenic and lead

This is very important as these are highly toxic metals. Specific tests are there to estimate
these two metals; products may not have excess of such metals.

Volatile matters and moisture
A specific amount of the product required to be taken in a dish and drying is to be done till
constant weight. Loss of weight will indicate percentage of moisture and volatile matters.
Effect of special ingredients

Special test should be done for the special ingredients if any, like antiseptics, enzymes, etc. for
each one special and specific test are to be done.
(4) LIQUID DENTAL PREPARATIONS

Use of liquid dentifrices are comparatively less than solid one.
They are basically aqueous or hydroalcoholic solutions of surfactants with additional
components like
Thickening agent
Sweeteners
Flavours etc.
They do not contain any abrasive as they will sediment
Action of this preparation on dental surface is less but the cleansing effect is more.
Manufacturing process is making solution of all ingredients.
Formulations
Formula :1
Sodium myristate sulphate 4.0 gm
Methyl cellulose 4.0 gm
Saccharine sodium 0.1 gm
Flavouring oil 0.3 gm
Glycerin 5.0 gm
Alcohol 10.0 gm
Water 85.4 gm
HALITOSIS
 Local factors, systemic factors, or a combination of both can cause halitosis.
 It is estimated that 80% of all mouth odors are caused by local factors within the oral
cavity, and these odors are most often associated with caries, gingivitis, and
periodontitis.
 Oral malodors occur because of the action of various microorganisms on proteinaceous
substances, such as, exfoliated oral epithelium, salivary proteins, food debris, and blood.
 Studies have shown that saliva from individuals who are free of dental disease produces
malodor less rapidly than saliva from patients with dental disease.
 It has also been observed that after prolonged periods of decreased salivary flow and
abstinence from food and liquid malodors tend to be most severe.
 Various oral bacteria produce products that are degraded to a number of compounds,
foremost of which are sulfides and mucoproteins.
 These compounds have been most often associated with oral malodor.
Specifically, it appears that oral malodor usually results from the bacterial- mediated
degradative processes of methyl mercaptan and hydrogen sulfide in oral air.
 Ammonia is also produced but does not appear to contribute significantly to halitosis.
 It has even been suggested that ammonia production may improve the odor of mouth
air.
 However, for many patients, systemic or local factors cannot be identified.
 Tongue scraping has been shown to reduce malodor in some patients.
 Mouthwashes and dentifrices can serve an esthetic function by reducing halitosis. They
can accomplish this by masking malodors, acting as antimicrobial agents, or both.
 There are no ADA-accepted products to reduce halitosis at this time.
Safety
 While dentifrice products have a long history of safety, there is an ongoing concern
associated with dental fluorosis due to fluoride ingestion in children under age six. Studies
have shown that for children 1–3 years, 30–75% of the dentifrice is ingested, and for
children 4–7 years 14–48% is ingested.
 As with any OTC drug product, precautions need to be taken to prevent overdose. The
FDA requires labeling of all fluoride dentifrice products to include a statement "to
minimize swallowing use a pea-size amount in children under six."
 Making childproof caps available on fluoride dentifrice products intended for use by
children has been recommended.
 Another approach would be to provide metered dentifrice delivery systems for children
under age six, which could be set to dispense the correct amount of fluoride depending on
the body weight of the child.
Dental care products

 Effervescent Polident Denture Cleansers
Non abrasive cleaning and antibacterial action in a soaking solution with
oxidizing agents and detergents to remove food particles, stains and
bacteria. Cleaning action is available in variants for 3 minutes, overnight
and stain removing whitening and for partials.
 Polident Fresh Cleanse Denture Foam

Denture Cleansing foam provides non abrasive mechanical cleaning and
antibacterial action and stain removal with detergents and a long lasting
flavor
 Polident Dentu-Paste and Dentu- Gel Denture

Cleansers
Mechanical cleaning with a brush using these denture cleansers
containing detergents and oxidizing agents

 Super Poligrip Denture Adhesive Cream
Poly (methylvinylether/maleic polymer cross linking salts to
provide adhesion between denture and the alveolar ridge and
the palate. The denture adhesive cream fills gaps between gum
and denture for a strong hold and sealing out food particles
 Super Poligrip Denture Adhesive Powder

Poly(methylvinylether/maleic polymer cross linking salts to provide
adhesion between a denture and the alveolar ridge and the palate. The
denture adhesive powder forms a strong, thin seal to keep out food
particles
 Super Poligrip Denture Adhesive Strips

Extruded strip with a Polyox/Carboxymethylcellulose system. The denture
adhesive strips are pre cut to control the amount of the application.
Texas Dental Firm Offers Novel Tooth-Whitening Product Line

 Ultra-White Products, Inc., a tooth whitening product manufacturer in Texas, now
offers an attractive alternative to marginally effective over-the-counter tooth
whitening product lines and costly dental treatments.
 The company’s novel tooth whitening product affords users the ability to obtain
custom application trays and whitening gels at a fraction of the cost normally
associated with professional cosmetic dentistry and are far more effective than
Over-the-counter solutions.
 The company has a worldwide following with over 30,000 clients and is owned an
managed by a practicing dentist.
NEWER FORMULATIONS OF DENTIFRICE FROM CHEMICAL ABSTRACTS

 Functional toothpaste containing nano sized silver.
 High Fluoride ion recovery dentifrice compositions.
 Stable Suspensions of composite material s for use as dentifrices containing an
antimicrobial organic acid salt.
 Application of water soluble chitosan in toothpaste & mouthwash.
 Dentifrice containing silica microparticles as the sole abrasives.
 Dentifrice compositions comprising alkyl galactoside derivatives +nonionic
disinfectants or +protein naturants or +vit- E gives strong coaggregation-inhibitory
effect & antibacterial effect against Fusobacterial & other dental caries & periodontal
disease- causing bacteria.

QUESTIONS:-
1) Define cosmetics? Put some light on its origin and development through different
ages.
2) Describe in brief the cosmetics products for skin?
3) Define shampoo? Write note about it?
4) Write a note on skin colorants?
5) Classify cosmetics with examples?
6) Define cosmoceutical? How it differs from cosmetics products? explain
7) Describe different nail preparations?
8) Write in detail about quality control of cosmetics including sampling size?
9) What is powder? Classify powers ? Give formulation of any one type?
10) Classify raw materials of cosmetics? Write in brief about each with example?

PHARMAROCKS GPAT SUCCESS TEST SERIES-2015 PARENTRAL PREPARATION
Parenteral Preparations
Syllabus:
Types- General requirements, Various components, container, closure, production facilities, procedures and equipment
employed in the manufacture of parenterals.
Freeze drying of parenteral formulations, quality control and packaging of parenterals. Study of official preparations
like, water of injection, Calcium gluconate injection.
References
1. Remington’s Pharmaceutical Sciences
2. Ansel Pharmaceutical Dosage Forms and Drug Delivery Systems
3. Banker Rhodes
4. Cooper & Gunn Dispensing
PARENTERAL PREPARATIONS
Definition:
The word ‘parenteral’ came from the Greek work ‘para enteron’ that means ‘beside the intestine’. So parenteral
products mean the dosage forms those deliver drugs through a route other than oral route.
Types of injections
Injections may be classified according to the route of administration, which is given in the tabular form under Routes of
Administration.
Intradermal injection
They are made into the skin between the inner layer or dermis, and the outer layer, or epidermis. The skin of
the front of the left forearm is usually selected. Other details are given in the table. The drug is injected into the dermis
of skin raising a bleb (e.g. BCG vaccine, sensitivity testing of drugs) or scarring / multiple puncture of the epidermis
through a drop of the drug (small pox vaccine) is done.
This route is employed for testing of allergen, such as pollens, dust or microorganisms (tuberculin or
histoplasmin).
Absorption is very small from this site because very small number of blood capillaries are present. The site
should not be massaged.
Body sites of injection: Usually on the outer surface of the left forearm.
Subcutaneous (or Hypodermic) injection

These injections are made under the skin, into the subcutaneous tissue. The drug is deposited in the loose
subcutaneous tissue which is richly supplied by nerves (so irritant drugs cannot be injected) but is less vascular (so
absorption is slower).
Care must be taken to ensure that the needle is not in a blood vessel. This is checked by lightly pulling back
the syringe plunger (a method known as aspiration) before making an injection. If the needle has pierced into a vessel
then blood will appear in the syringe and in that situation the injection should not be made.
Sometimes dextrose and electrolyte solutions are given subcutaneously in amounts from 250 to 1000mL. This
technique is called hypodermoclysis. This method is used when veins are not available in a patient or are difficult to use
for further medication. In this case the hyalouronidase is co-administered with the large volume injection (LVP) that
helps in hydrolysis of hyalouronic acid (the cell-cementing material that binds the cells of the tissues), increases the
absorption of the liquid and decrease tissue distension.
Body sites of injection: Usually on the most portions of arms, legs and abdomen.
Advantages:
1. Self injection is possible because deep penetration is not required.
2. oily solutions or aqueous suspensions can form a depot which will release drug slowly for a prolonged period.
Disadvantages:
1. Since skin is richly supplied by nerve-endings hence irritant drugs cannot be injected.
2. Drugs administered in this route produce slower onset of action than i.m. or i.v. route.
3. This route should be avoided in shock patients.
e.g. Insulin injection.

Intramuscular injection
The drug is injected in one of the large skeletal muscles that lie below the subcutaneous layer.
Body sites of injection: Deltoid (upper arm), gluteal (buttock), vastus lateralis (lateral thigh) msucles.
It is important to aspirate before injection to ensure that the needle does not enter into a vein.
Advantages:
1. Muscle is less richly supplied with sensory nerves, hence mild irritants can be injected.
2. Muscle is more vascular hence absorption is faster (onset of action 15 to 30mins) than subcutaneous route.
3. It is less painful.
4. Depot preparations can be injected by this route and the action of the drug may be prolonged.
Disadvantages:
1. Since deep penetration is needed hence self-medication is not possible.
2. Large volume cannot be given.
e.g. Low volume injections - Vitamin A, hydrocortisone acetate, tetanus toxoid, antibiotic etc.
Intravenous injection
The drug is injected as a bolus (venipuncture) or infused slowly over hours (venoclysis) in one of the
superficial veins (generally medial basilic vein).
Rug must be administered through this route slowly because irritation or an excessive drug concentration at sensitive
organs such as the heart and brain (drug shock) may occur.
The duration of action of a drug depends on the pharamcokinetic parameters (rate of distribution and elimination)
Advantages:
(i) The drug directly reaches the blood stream and effect is produced immediately, hence, this route can
be used in emergencies.
(ii) The inside of the veins is insensitive (because no nerve endings are there) and drug gets diluted with
blood quickly, therefore, even highly irritant drugs can be injected intravenously.
(iii) Large volumes can be infused (e.g. normal saline).
(iv) It is useful in unconscious patients.
(v) Desired blood concentration can be achieved.
Disadvantages:
(i) Drugs that precipitate in the blood cannot be administered. Only aqueous solution can be
administered.
(ii) If the needle puncture the vessel (i.e. extra vasation) then thrombophlebitis of the injected vein and
necrosis of the adjoining tissues may occur.
(iii) No drug can be given in depot form - so the action is not prolonged compared to other parenteral
administrations.
(iv) Untoward reactions if occur are immediate.
(v) Once administered, withdrawal of the drug is not possible.
Intra-arterial injection
The intra-arterial route involves injecting a drug directly into an artery. It is important that the artery not be missed,
since serious nerve damage may occur to the nerves lying close to the arteries.
Dose given through this route must be minimum and given gradually, since, once injected, the drug effect cannot be
neutralized.
This route of injection is used to administer radiopaque contrast media for viewing an organ, such as the heart or
kidney, or to perfuse an antineoplastic agent at the highest possible concentration to the target organ.
Intrathecal injection
The intrathecal route is employed to administer a drug directly into the cerebrospinal fluid at any level of the
cerebrospinal axis. This route is used when it is not possible to achieve sufficiently high plasma levels to accomplish
adequate diffusion and penetration into the cerebrospinal fluid. Intrathecal, intraspinal, and intracisternal routes must be
formulated at physiologic pH, must be isotonic and must not contain any preservatives in order to minimize nerve
damage.
Local anaesthetic drugs are injected through this routes.
Specialized Large-Volume Parenteral and Sterile solutions

Large volume parenterals are designed to provide fluid (water), calories (dextrose solutions), electrolytes (saline
solutions), or combinations of these materials.

Hyperalimentation solution (Total Parenteral Nutrition)

Parenteral hyperalimentation involves administration of large amount of nutrients (e.g. carbohydrates, amino acids,
lipids and vitamins) to maintain a patient who is unable to take food orally for several weeks at caloric intake levels of
4000kcal/day or more. The formulation when administered through a peripheral vein intravenously at a slower rate the
body does not get enough nutrition, so this type of LVP is given as hypertonic solution and given through subclavian
vein so the liquid gets diluted very quickly with the blood. This formulation generally consists commonly a mixture of
dextrose, amino acids and lipids (usually soybean oil, sunflower oil or mixture of two) containing added electrolytes,
trace metals and vitamins.
Nutrition is supplied in this method to comatose patients, patients undergoing oesophageal obstruction, GI disease
(including GI cancer), ulcerative colitis, etc.
Cardioplegic solutions
Cardioplegic solutions are large-volume parenteral solutions used in heart surgery to help prevent ischemic injury to the
myocardium during the time the blood supply to the heart is clamped off and during reperfusion, as well as to maintain
bloodless operating field and to make the myocardium flaccid.
This solutions are typically electrolyte solutions where the electrolyte composition is intended to maintain diastolic
arrest.
These solutions are administered in cold condition in order to cool the myocardium and minimize metabolic activity.
These solutions are slightly alkaline and hypertonic in order to minimize acidosis and to minimize reperfusion injury
resulting from tissue edema.
Peritoneal dialysis solutions

The sterile peritoneal dilysis solutions are infused continuously into the abdominal cavity, bathing the peritoneum, and
are then continuously withdrawn.
The purpose of peritoneal dialysis is to remove toxic substances from the body and accelerates the excretion rate of the
drug from the body in case of acute renal insufficiency.
These types of formulations contains
(a) glucose and ionic content similar to extraceular fluid. In some cases hypertonic glucose solutions are prepared to
draw excess fluid from the patient.
(b) An antibiotic is often added to this solutions as a prophylactic measure.
Irrigating solutions
Irrigating solutions are intended to irrigate, flush, and aid in cleansing body cavities and wounds.
Normal saline may be used as irrigating solution.
Irrigating solutions are sterile and pyrogen free because while it is used to wash the wounds small amount of solution
infuses inside the wound.
Formulation factors
The formulation of injections involves careful consideration of the following factors:
1. The route of administration
2. The volume of injection
3. The vehicle in which the medicament is to be dissolved or suspended.
4. The osmotic pressure of the solution.
5. The need for a preservative.
6. The pH of the solution.
7. The stability of the drug.
1. Routes of administration
Routes Usual Needle Formulation constraints Types of medication administered

volume Used
Length / Dia
Subcutaneous 0.5-2ml 5/8in 23gauge Must be isotonic Insulins, vaccines
Intramuscular 0.5-2ml 1.5in, 22gauge Can be oils, suspensions, Nearly all types of drugs.
emulsion.
Preferably isotonic.
Intravenous
Small volume 1-1000ml Veinpunture Solutions, emulsions and Nearly all types of drugs
1.5in,20-22gauge liposomes
Large volume 101 and Venoclysis Solutions and some emulsions Nearly all types of drugs

(infusion) above 1.5in, 18-19gauge (TPN)

Intra-arterial 2-20ml 20-22gauge Solutions and some emulsions Radiopaque media, antineoplastics,
(Directly into an artery) antibiotics.
Intrathecal 1-4ml 24-28gauge Must be isotonic Local anaesthetics, analgesics,
(into spinal canal) neurolytic agents.
Intraepidural 6-30ml 5in,16-18gauge Must be isotonic Local anaesthetics, narcotics, 2-
(into epidural space near agonists, steroids.
spinal cord)
Intracisternal Must be isotonic
(directly into caudal region
of the brain between the
cerebellum and medula
oblongata)
Routes Usual Needle Formulation constraints Types of medication administered

volume Used
Length / Dia
Intra-articular 2-20ml 1.5-2in, Must be isotonic Morphine, local anaesthetics,
(directly into a joint) 18-22 gauge steroids, NSAIDs, antibiotics.
Intracardial 0.2-1 5 in Cardiotonic drugs (epinephrine),
(directly into the heart) 22gauge calcium.
Intrapleural 2-30ml 2-5 in Local anaesthetics, narcotics,
(directly nito the pleural 16-22 gauge chemotherapeutic agents
cavity of the lung)
Intradermal 0.05ml ½ - 5/8 in, Should be isotonic Diagnostic agents for investigation of
25-26 gauge immunity and allergy to any agent.

2. Volume of injection
Usually the volume of an injection depends on the route of administration. Only the intravenous route is really suitable
for large volume parenterals (LVP). In subcutaneuous route generally 0.5-2ml volume may be injected. Some times
veins of a patient are unavailable. In those cases instead of intravenous infusion large volume parenterals (250 to
1000ml) may be injected subcutaneously. This technique is called hypodermoclysis. In most of this case the injection is
given along with hyalouronidase an enzyme that hydrolyses the hyalouronic acid, the viscous cell-cementing agent. It
helps in rapid absorption of the injection and reduces tissue distension. The hydrolysis is reversible and the acid is
reformed in about 20minutes after completion of the injection.
The volume must be convenient to administer. Less than 20ml is suitable for injection with a syringe and more than
250ml injections are given as infusion.

GPAT SUCCESS TEST SERIES-2015: THE WAY OF SUCCESS CALCULATION FORMULA
PHARMAROCKS GPAT SUCCESS TEST SERIES 2015 CALCULATION FORMULA
MOST IMPORTANT FORMULA USE IN POSOLOGY CALCULATION

1. Young’s Rule: Child dose = [Age X Adult dose] / (Age + 12)
2. Couling’s Rule: Infant dose = [Age (at next birthday) X Adult dose] / 24
3. Fried’s Rule: Infant dose = [Age (in months) X Adult dose] / 150
4. Clark’s Rule: Child dose = [Weight (in lbs) X Adult dose] / 150
DENSITY = MASS / VOLUME
SPECIFIC GRAVITY (Sp. gr.)

Sp. gr. = Wt / V
Sp. vol = V / Wt thus sp. volume = 1 / sp. gr
Wt. of the liquid = sp. gr. of liquid X volume of the liquid

Volume of a liquid = Wt of liquid / sp. gr.
Strength X Volume = Strength X Volume
CALCULATION OF TEMPERATURE
9 X oC = 5 X oF -160
Proof Gallon = Wine gallon X Proof strength / 50%
ISOTONICITY
 Sodium chloride 0.90%
 Dextrose 5.00%
 Boric acid 1.73%
FREEZING POINT DEPRESSION OF NORMAL SALINE IS 0.52
The equivalent weight = Molecular weight / valency

Mosmol = m moles X no of ions = (wt in mg / m wt) X no of ions

GPAT SUCCESS TEST SERIES-2015: THE WAY OF SUCCESS CALCULATION FORMULA
pH = – Log [ H+]
pOH = – log [OH]
pH = pKw – pOH = 14 – pOH
pKa = - log [Ka]
pKb = - log [Kb]
pH = pKa + log [ Salt / Acid ]
pH = pKa + log [ Base / Salt ]
pH = pKw – pKb + log [ Base / Salt ]
Sensitivity requirement = minimum quantity to be weighed in mg X permissible error

PHARMAROCKS
GPAT STUDY MATERIAL
ALKALOIDS
PHARMACOGNOSY

ORGANISE BY MR. AMAR M. RAVAL
ALKALOIDS: SOME IMP POINTS AND DRUGS

Alkaloids are basic nitrogen containing compounds obtained from plants, animals &
microorganisms having a marked physiological action
Characteristics:
Well defined crystalline substances, generally occurring as solids except nicotine which is a
liquid, colourless except berberine which is a yellow coloured alkaloid. Occur in plants in the
salt form.
They answer the following chemical tests:
1. Mayer’s reagent- (potassium mercuric iodide)
Cream coloured precipitate
2. Wagner’s reagent- (iodine in potassium iodide)
Reddish brown precipitate
3. Hager’s reagent- (salt solution of picric acid)
Yellow precipitate
4. Dragendroff’s reagent- (potassium bismuth iodide)
Caffeine is a pseudo alkaloid drug which does not answer this test
Extraction:
 The powdered drug is defatted using petroleum ether if necessary
 The powder is further basified using lime to break the salt form of the alkaloid &
liberate free base which can be extracted using an organic solvent
 Alkaloidal salts can be directly extracted using an acidified aqueous solvent
Classification:
1. Pharmacological method
2. Taxonomic method
3. Biosynthetic method
4. Chemical method – true & proto alkaloids
 TRUE ALKALOIDS
1. Pyrrole & Pyrrolidine Eg- Coca
2. Pyridine & Piperidine Eg- Coniine
3. Tropane Eg- Atropine
4. Quinoline Eg- Cinchona

5. Indole Eg- Rauwolfia
6. Purine Eg- Caffeine
7. Steroidal Eg- Kurchi
8. Isoquinoline Eg- Opium
 PROTO ALKALOIDS
Eg- Ephedrine
INDOLE ALKALOIDS
ERGOT / ARGOT / ST. ANTHONY’S FIRE
BIOLOGICAL SOURCE:
Schlerotium of fungus claviceps purpurea, at the ovary of rye plant secale cereale
Family: graminae (fungus belongs to family clavicipitaceae)
GEOGRAPHICAL SOURCE: Switzerland

Known to have caused gangrene (ergotism) in Germany
Life cycle:
1. Sexual / sphacelial stage
2. Asexual / schlerotium stage
Sexual stage:
The ascospores infect the ovary of the rye plant & if conditions are favourable it develops
hyphal strands, it forms a white mass over the ovary known as the mycelium
Asexual stage:
The hyphal strands further develop invading the ovary & converting it to a hard violet
schlerotium, Schlerotium contains stromatum which shows a globular stalk
It encloses bag like structures known as ascus containing ascospores
If these ascospores are liberated they infect another rye plant
Morphology of schlerotium:
Hard, violet, odourless, with an unpleasant taste
Chemistry:
Derivatives of lysergic acid

Water soluble ones are ergometrine & ergometrinine

Water insoluble ones are ergotamine & ergotoxine
Only the levo isomer is active
Uses:
Ergometrine is an oxytocic drug but its methyl derivative is preferred as it causes less
hypertension
Ergotamine is analgesic in migraine
Chemical Test:
1. Gives a blue colour with Van Curk’s reagent (para dimethyl amino benzaldehyde)
2. Gives blue fluorescence in water
3. When treated with ether, H2SO4 followed by sodium bicarbonate, aqueous layer shows a
red violet colour
4. Ergotamine + glacial acetic acid + ethyl acetate + H2SO4 gives a blue solution with a red
tinge. When further treated with FeCl3 the blue colour disappears
VINCA / PERIWINKLE
BIOLOGICAL SOURCE: aerial parts of catharanthus roseus

Family: apocynaceae
GEOGRAPHICAL SOURCE: India, Madagascar
Morphology:
Leaves are small, opaque, dark green, odourless & bitter to taste
Chemistry:
Indole alkaloids such as vinblastine, vincristine, ajamlicine & serpentine
Use:
Potent anti-cancer agent, hypotensive & anti-diabetic

NUXVOMICA
BIOLOGICAL SOURCE: dried seeds of strychnos nuxvomica

Family: Loganiaceace
GEOGRAPHICAL SOURCE: srilanka, India
MORPHOLOGY:
Seeds are circular, flat, grayish green, covered with trichomes & extremely bitter to taste
Chemistry:
Contains two main indole alkaloids strychnine & brucine
Use:
Rarely used as a nerve tonic as it is poisonous in large doses
Chemical Test:
1. Section when treated with concentrated HNO3 shows a yellow colour with brucine
2. Section when treated with ammonium vanadate & H2SO4 shows a purple colour with
strychnine
3. Strychnine when treated with H2SO4 & K2Cr2O7 develops a violet to yellow colour
RAUWOLFIA / SARPAGANDHA
BIOLOGICAL SOURCE: dried roots of rauwolfia serpentina

Family: apocynaceae
GEOGRAPHICAL SOURCE: Asia, America
Morphology:
Snake shaped, brown coloured, longitudinal wrinkles tapering towards the end
Chemistry:
Reserpine, ajamlicine, serpentine

Use:
Antihypertensive by preventing uptake of adrenaline
Chemical Test:
1. Freshly fractured surface of the root when treated with concentrated HNO3 shows red
coloured medullary rays
2. Reserpine gives a violet colour with vanillin in acetic acid
TROPANE ALKALOIDS
BELLADONA
BIOLOGICAL SOURCE: dried leaves of atropa belladonna

Family: solanaceae
GEOGRAPHICAL SOURCE: England, Europe, India
Morphology:
Leaves are greenish brown, ovate in shape with an entire margin & bitter to taste
Microscopic Characters:
 Dorsiventral leaf
 Collenchyma above & below the mid rib
 Unicellular covering trichomes, unicellular glandular trichomes
 Microsphaenoidal calcium oxalate crystals
Chemistry:
Atropine, hyoscyanine, belladonine
Use:
Atropine is a parasympatholytic, thus decreases secretion & spasms
Chemical Test:
Vitali morin test – to the drug fuming nitric acid is added & it is evaporated to dryness.
Methanolic KOH is added to the acetone solution of the nitrated residue
It develops a violet colour
STRAMONIUM
BIOLOGICAL SOURCE: dried leaves & flowering tops of datura stramonium

Family: solanaceae
GEOGRAPHICAL SOURCE: America, France
Morphology:
Leaves are grayish green with a crenate margin & unequal base
 Unicellular covering & glandular trichomes
 Xylem surrounded by phloem
 Anisocytic stomata
Chemistry:
Hyoscine, atropine, belladonine
Use:
Hyoscine is an anti-emetic
Chemical Test:
Vitali morin test
COCA LEAVES
BIOLOGICAL SOURCE:
Dried leaves of erythroxylon coca (Bolivian variety) Erythroxylon truxillense (Peruvian
variety)
Family: erythroxylaceae
GEOGRAPHICAL SOURCE: Bolivia, Peru
Morphology:
Peruvian leaves are pale green, fragile, thin, and elliptical in shape
Bolivian leaves are greenish brown, oval in a shape with a prominent mid rib
 Collenchyma above & below mid rib
 Xylem surrounded by phloem & pericyclic fibres
 Paracytic stomata
Chemistry:
Cocaine, cinnamoyl cocaine, tropocaine, benzoylecgonine
Extraction:
The leaf powder is basified with lime & extracted using an organic solvent
The free bases are converted to their hydrohlorides by using HCl
Due to this procedure cocaine liberates ecgonine, methanol & benzoic acid whereas cinnamoyl
cocaine generates ecgonine, methanol & cinnamic acid
The ecgonine thus obtained is used to synthesize cocaine by treating it with benzoic anhydride,
methyl iodide, and methanol & sodium methoxide
Use:
Local anaesthetic
Chemical Test:
Drug powder when heated with concentrated H2SO4 gives a typical odour of methyl benzoate
QUINAZOLINE ALKALOIDS
VASAKA LEAF / ADULSA
BIOLOGICAL SOURCE: dried & fresh leaves of adhatoda vasica

Family: acanthaceae
GEOGRAPHICAL SOURCE: India
Morphology:
Leaves are dark green, lanceolate in shape, have a crenate margin with a characteristic odour
& bitter taste
Chemistry:
Vasicine, vasicinone & adhatodic acid
Uses:
Vasicine is an expectorant. It gets oxidized to vasicinone which in an abortifacient in large
doses, otherwise a bronchodilator
PYRIDINE ALKALOIDS
LOBELIA HERB / INDIAN TOBACCO / ASTHMA WEED
BIOLOGICAL SOURCE: dried aerial parts of lobelia nicotianefolia

Family: campanulaceae
Morphology:
Leaves are sessile, large, dark green & possess an acrid taste
Chemistry:
Lobeline, lobelidine & isolobanine
Use:
Respiratory stimulant
Chemical Test:
1. Lobeline solution if heated gives typical odour of acetophenone
2. Lobeline in H2SO4 when treated with formaldehyde develops red colour
IMIDAZOLE ALKALOIDS
PILOCARPUS
BIOLOGICAL SOURCE: dried leaves of pilocarpus jaborandi, Pilocarpus microphyllus
Family: rutaceae
GEOGRAPHICAL SOURCE: south America
Morphology:
Leaves are greyish green with an asymmetrical base & possesses aromatic odour & bitter taste
Chemistry:
Contains pilocarpine, pseudopilocarpine, pilosine & limonene
Uses:
Antagonist to atropine, causes miosis, increases salivation & sweating
Chemical Test:
Pilocarpine solution when treated with H2SO4, H2O2, benzene & K2Cr2O4, the organic layer
appears bluish violet in colour whereas aqueous layer shows yellow colour
INDOLE ALKALOIDS
CALABAR BEANS
BIOLOGICAL SOURCE: dried type seeds of physostigma venenosum

Family: leguminosae
GEOGRAPHICAL SOURCE: Africa
Morphology:
Reddish brown in colour, hard, shiny & rough to touch
Chemistry:
Contains physostigmine, starch & proteins
Use:
Helps in contraction of pupil, retards respiration & causes bradycardia
OPIUM / POPPY PLANT

BIOLOGICAL SOURCE: dried latex obtained from capsules of papaver somniferum
Family: papaveraceae
GEOGRAPHICAL SOURCE: India (MP), turkey, Pakistan, Afghanistan
Collection:
 Collection is started when capsules change colour from dark green to yellowish green.
 Longitudinal incisions about 2mm deep are given on the capsules to exude the latex
 The latex is allowed to solidify overnight & later scraped off
 The process is repeated 4 times with a gap of 2 days

Morphology:
The dried latex is dark brown, extremely bitter to taste & has a strong odour
Chemistry:
Contains phenanthrene type of alkaloids such as morphine & codeine & benzyl isoquinoline
type of alkaloids such as papaverine & noscapine
These occur as salts of meconic acid
Use:
 Morphine is a narcotic analgesic & stimulant
 Codeine is an anti tussive
 Papverine is a smooth muscle relaxant
Chemical Test:
1. Aqueous solution of meconic acid shows a deep reddish purple colour with ferric chloride
2. Morphine when sprinkled with concentrated HNO3 shows an orange red colour. This is
not allowed by codeine
3. Morphine solution when treated with ferric chloride & potassium ferricyanide gives a
bluish green colour
4. Papaverine solution in HCl & potassium ferricyanide develops a lemon yellow colour
Varieties of opium:
Indian, Turkish, Persian, European, manipulated Persian & European
QUINOLINE AKALOIDS
CINCHONA BARK / JESUIT’S BARK / PERUVIAN BARK
BIOLOGICAL SOURCE:
Dried bark of cultivated trees of cinchona calisaya
Cinchona officinalis
Cinchona ledgeriana
Cinchona succirubra
Family: rubiaceae
GEOGRAPHICAL SOURCE: India, Bolivia, srilanka

Collection:
It is collected by coppicing method
Vertical incisions are made on branches, trunk of the tree & these incisions are connected by
horizontal circles
The bark is then stripped off & dried in sunlight & further by artificial heat (175 degree F)
The root bark is collected by uprooting trees & separating manually
Morphology:
Stem bark is rough with transverse fissures
Outer surface is grey & inner surface is pale yellowish brown to deep reddish brown
Root bark is curved, outer surface is scaly, outer & inner surface with same colour
 Cork cells are thin walled
 Cortex has phloem fibres
 Medullary rays with radially arranged cells
 Idioblast of calcium oxalate is a specific characteristic
 Starch grains in parechymatous tissues
 Stone cells rarely present
Chemistry:
Contains quinine, quinidine, cinchonine & cinchonidine
Also contains quinic acid & cinchotannic acid
Chemical Test:
1. On heating the drug in a dry test tube with glacial acetic acid, purple vapours are produced
2. Thalleoquin test: drug + bromine water + dilute ammonia gives an emerald green colour
3. Drug when treated with quinidine solution gives a white precipitate with silver nitrate
which is soluble in nitric acid
Uses:
Anti-malarial, anti-pyretic, quinine is used in arrhythmias against atrial fibrillation

ISOQUINOLINE ALKALOIDS
IPECAC
BIOLOGICAL SOURCE:
Dried roots of cephalis ipecacuanha (Brazilian / Rio), Cephalis acuminata (panama / Cartagena)
Family: rubiaceae
GEOGRAPHICAL SOURCE: Brazil, panama
Morphology:
Brazilian ipecac is dark brick red as compared to greyish brown panama ipecae
Both possess faint odour & bitter taste
Chemistry:
Brazilian – emetine: cephalin ratio is 4:1
Panama – emetine: cephalin ratio is 1:1
Uses:
Expectorant in mild doses & as an emetic in large doses
Emetine also possesses anti protozoal activity
Chemical Test:
1. Emetine shows a bright green colour with H2SO4 & molybdic acid
2. Emetine when shaken with water & small amount of HCl, filtered & to the filtrate potassium
chlorate is added gives a yellow colour changing to red
PYRIDINE- PIPERIDINE ALKALOIDS

TOBACCO
BIOLOGICAL SOURCE: dried leaves of nicotiana tabacum
Family: solanaceae
GEOGRAPHICAL SOURCE: India, France
Morphology:
Leaves are large, green with a dentate margin
It has a characteristic strong odour & bitter taste
Chemistry:
Nicotine, nornicotine & anabasine
Use:
Stimulant
PROTO ALKALOIDS
EPHEDRA / MA HUANG
BIOLOGICAL SOURCE: dried stem of ephedra gerardiana
Family: ephedreaceae / gnetaceae
GEOGRAPHICAL SOURCE: china, Pakistan
Morphology:
Greyish green, thin, cylindrical stem bearing scaly leaves & internodes
No typical odour but has a bitter taste
Chemistry:
Contains amino alkaloids like ephedrine, norephedrine & pseudo ephedrine
Uses:
Sympathomimetic & bronchodilator
Chemical Test:
Aqueous solution of ephedrine shows a violet colour when treated with dilute HCl & CuSO4
followed by dilute NaOH
COLCHICUM / AUTUMN CROCUS

BIOLOGICAL SOURCE: dried seeds & corms of colchicum luteum
Family: liliaceae
GEOGRAPHICAL SOURCE: Europe
Morphology:
Seeds are hard, reddish brown, rough to touch whereas corms are yellowish in colour with a
longitudinal groove & bitter to taste
Chemistry:
Contains amino alkaloid colchicine & demecolchicine

Uses:
Rheumatism, treatment of gout, anti-tumour activity & polyploidy
ACONITE / BACHNAG
BIOLOGICAL SOURCE: dried roots of aconitum napellus
Family: ranunculaceae
GEOGRAPHICAL SOURCE: Germany, Spain
Morphology:
Roots are dark brown, longitudinally wrinkled & tapering towards one end
They have slight odour & taste
Chemistry:
Diterpene alkaloids such as aconitine, neopelline, neoline & small amount of ephedrine
Aconitine is an active constituent but if hydrolysed forms benzoyl aconine & aconine which
are less active
Uses:
Externally in neuralgia & sciatica
PSEUDO ALKALOIDS
COFFEE
BIOLOGICAL SOURCE: dried seeds of coffee Arabica
Family: rubiaceae
GEOGRAPHICAL SOURCE: southern part of India, Indonesia
Collection:
The unripe coffee fruit is dark green & is collected when it turns red
Each fruit has two locules containing one seed each
The seeds are separated, roasted because of which they develop a dark brown colour & a typical
odour
Chemistry:
Contains caffeine which is a salt of chlorogenic acid, volatile oil known as caffeol, enzymes &
other phenolic compounds
Uses:
Stimulant, diuretic (due to theophylline), & source of caffeine

Chemical Test:
1. Murexide test: caffeine when heated with HCl & potassium chlorate give a residue which
turns purple when exposed to ammonia vapours
2. Caffeine forms a white precipitate with tannin solution
TEA
BIOLOGICAL SOURCE: prepared leaves of thea sinensis
Family: theaceae
GEOGRAPHICAL SOURCE: India, srilanka
Collection:
The tea plant is a small green shrub wherein younger leaves are picked & allowed to undergo
fermentation
Polyphenol oxidase carries out oxidation to produce furfural & other phenolic compounds
The process imparts a dark brown or black colour & a typical odour of tea powder
For preparation of green tea, fresh leaves are dried & roasted in copper pans & finally powdered
Chemistry:
Contains caffeine, theophylline, theobromine, oxidase enzyme & tannins
Use:
Stimulant, diuretic, source of caffeine
Chemical Test:
Murexide test
KOLA NUTS / BISSY SEEDS

BIOLOGICAL SOURCE: seeds of cola nitida
Family: sterculiaceae
GEOGRAPHICAL SOURCE: west Africa, Brazil
Morphology:
Seeds are Plano convex in shape & reddish brown with a bitter taste
Chemistry:
Contains caffeine, theobromine & a red pigment known as kola catechin
Use:
Stimulant
COCOA SEEDS
BIOLOGICAL SOURCE: seeds of theobroma cacao
Collection:
The fruits are ellipsoidal in shape with a white pulp & contain about 40 to 50 seeds
Fermentation is carried out in boxes for about 3 days at a temperature below 60 degree Celsius
The seeds acquire a different coulour, taste & odour
Seeds are then roasted to evaporate the water
It also facilitates removal of the seed coat
Seeds are then powdered to obtain cocoa powder
Chemistry:
Caffeine. Theobromine, other phenolic compounds
Use: Stimulant
STEROIDAL ALKALOIDS
KURCHI
BIOLOGICAL SOURCE: dried bark of holarrhena antidysenterica
Family: apocynaceae
Chemistry:
Steroidal alkaloid conessine & norconessine
Use:
Amoebic dysentery
ASHWAGANDHA
BIOLOGICAL SOURCE: dried roots of withania somnifera
Family: solanaceae
GEOGRAPHICAL SOURCE: India, Afghanistan
Morphology:
Roots are cylindrical, buff coloured, have a characteristic odour & are tasteless
Outermost layer of cork cells followed by cortex
Vascular bundle consists of phloem parenchyma & xylem blocking the pith
Chemistry:
2 types of chemical constituents

1. Steroidal lactones called withanolides like withaferine
2. Alkaloids like withanine, somniferine, anaferine
Also contains alcohols known as somnitol & somnirol
Uses:
Sedative, hypnotic, hypotensive & immunomodulatory
PYRAZOLINE ALKALOIDS
PEPPER
BIOLOGICAL SOURCE: dried fruits of piper nigrum
Family: piperaceae
GEOGRAPHICAL SOURCE: south India, Indonesia
Morphology:
Fruits are green when unripe but turn dark black after drying
The dried fruits are wrinkled with an aromatic odour & pungent taste
Chemistry:
Alkaloid piperine is responsible for pungent taste aong with piperetine, resins, volatile oils
containing limonene & pinen responsible for the odour
Uses:
Bronchitis & gonorrhoea
 DO OTHER TOPICS FROM BOOK C.K KOKATE
 DO MICROSCOPY FROM KHANDELWAL BOOK
 THE TABLES GIVEN IN C.K KOKATE ARE IMP FOR GPAT EXAM
 PREPARE WELL ALL THE TABLES GIVEN IN C.K. KOKATE BOOK

PHARMAROCKS
GPAT STUDY MATERIAL
ALKALOIDS
PHARMACOGNOSY

ORGANISE BY MR. AMAR RAVAL
ALKALOIDS: SOME IMP POINTS AND DRUGS

Alkaloids are basic nitrogen containing compounds obtained from plants, animals &
microorganisms having a marked physiological action
Characteristics:
Well defined crystalline substances, generally occurring as solids except nicotine which is a
liquid, colourless except berberine which is a yellow coloured alkaloid. Occur in plants in the
salt form.
They answer the following chemical tests:
1. Mayer’s reagent- (potassium mercuric iodide)
Cream coloured precipitate
2. Wagner’s reagent- (iodine in potassium iodide)
3. Hager’s reagent- (salt solution of picric acid)
Yellow precipitate
4. Dragendroff’s reagent- (potassium bismuth iodide)
Caffeine is a pseudo alkaloid drug which does not answer this test
Extraction:
 The powdered drug is defatted using petroleum ether if necessary
 The powder is further basified using lime to break the salt form of the alkaloid &
liberate free base which can be extracted using an organic solvent
 Alkaloidal salts can be directly extracted using an acidified aqueous solvent
Classification:
1. Pharmacological method
2. Taxonomic method
3. Biosynthetic method
4. Chemical method – true & proto alkaloids
 TRUE ALKALOIDS
1. Pyrrole & Pyrrolidine Eg- Coca
2. Pyridine & Piperidine Eg- Coniine
3. Tropane Eg- Atropine
4. Quinoline Eg- Cinchona

5. Indole Eg- Rauwolfia
6. Purine Eg- Caffeine
7. Steroidal Eg- Kurchi
8. Isoquinoline Eg- Opium
 PROTO ALKALOIDS
Eg- Ephedrine
INDOLE ALKALOIDS
ERGOT / ARGOT / ST. ANTHONY’S FIRE
BIOLOGICAL SOURCE:
Schlerotium of fungus claviceps purpurea, at the ovary of rye plant secale cereale
Family: graminae (fungus belongs to family clavicipitaceae)
GEOGRAPHICAL SOURCE: Switzerland

Known to have caused gangrene (ergotism) in Germany
Life cycle:
1. Sexual / sphacelial stage
2. Asexual / schlerotium stage
Sexual stage:
The ascospores infect the ovary of the rye plant & if conditions are favourable it develops
hyphal strands, it forms a white mass over the ovary known as the mycelium
Asexual stage:
The hyphal strands further develop invading the ovary & converting it to a hard violet
schlerotium, Schlerotium contains stromatum which shows a globular stalk
It encloses bag like structures known as ascus containing ascospores
If these ascospores are liberated they infect another rye plant
Morphology of schlerotium:
Hard, violet, odourless, with an unpleasant taste
Chemistry:
Derivatives of lysergic acid

Water soluble ones are ergometrine & ergometrinine

Water insoluble ones are ergotamine & ergotoxine
Only the levo isomer is active
Uses:
Ergometrine is an oxytocic drug but its methyl derivative is preferred as it causes less
hypertension
Ergotamine is analgesic in migraine
Chemical Test:
1. Gives a blue colour with Van Curk’s reagent (para dimethyl amino benzaldehyde)
2. Gives blue fluorescence in water
3. When treated with ether, H2SO4 followed by sodium bicarbonate, aqueous layer shows a
red violet colour
4. Ergotamine + glacial acetic acid + ethyl acetate + H2SO4 gives a blue solution with a red
tinge. When further treated with FeCl3 the blue colour disappears
VINCA / PERIWINKLE
BIOLOGICAL SOURCE: aerial parts of catharanthus roseus

Family: apocynaceae
GEOGRAPHICAL SOURCE: India, Madagascar
Morphology:
Leaves are small, opaque, dark green, odourless & bitter to taste
Chemistry:
Indole alkaloids such as vinblastine, vincristine, ajamlicine & serpentine
Use:
Potent anti-cancer agent, hypotensive & anti-diabetic

NUXVOMICA
BIOLOGICAL SOURCE: dried seeds of strychnos nuxvomica

Family: Loganiaceace
GEOGRAPHICAL SOURCE: srilanka, India
MORPHOLOGY:
Seeds are circular, flat, grayish green, covered with trichomes & extremely bitter to taste
Chemistry:
Contains two main indole alkaloids strychnine & brucine
Use:
Rarely used as a nerve tonic as it is poisonous in large doses
Chemical Test:
1. Section when treated with concentrated HNO3 shows a yellow colour with brucine
2. Section when treated with ammonium vanadate & H2SO4 shows a purple colour with
strychnine
3. Strychnine when treated with H2SO4 & K2Cr2O7 develops a violet to yellow colour
RAUWOLFIA / SARPAGANDHA
BIOLOGICAL SOURCE: dried roots of rauwolfia serpentina

Family: apocynaceae
GEOGRAPHICAL SOURCE: Asia, America
Morphology:
Snake shaped, brown coloured, longitudinal wrinkles tapering towards the end
Chemistry:
Reserpine, ajamlicine, serpentine

Use:
Antihypertensive by preventing uptake of adrenaline
Chemical Test:
1. Freshly fractured surface of the root when treated with concentrated HNO3 shows red
coloured medullary rays
2. Reserpine gives a violet colour with vanillin in acetic acid
TROPANE ALKALOIDS
BELLADONA
BIOLOGICAL SOURCE: dried leaves of atropa belladonna

Family: solanaceae
GEOGRAPHICAL SOURCE: England, Europe, India
Morphology:
Leaves are greenish brown, ovate in shape with an entire margin & bitter to taste
 Unicellular covering trichomes, unicellular glandular trichomes
 Microsphaenoidal calcium oxalate crystals
Chemistry:
Atropine, hyoscyanine, belladonine
Use:
Atropine is a parasympatholytic, thus decreases secretion & spasms
Chemical Test:
Vitali morin test – to the drug fuming nitric acid is added & it is evaporated to dryness.
Methanolic KOH is added to the acetone solution of the nitrated residue
It develops a violet colour
STRAMONIUM
BIOLOGICAL SOURCE: dried leaves & flowering tops of datura stramonium

Family: solanaceae
GEOGRAPHICAL SOURCE: America, France
Morphology:
Leaves are grayish green with a crenate margin & unequal base
 Unicellular covering & glandular trichomes
 Xylem surrounded by phloem
 Anisocytic stomata
Chemistry:
Hyoscine, atropine, belladonine
Use:
Hyoscine is an anti-emetic
Chemical Test:
Vitali morin test
COCA LEAVES
BIOLOGICAL SOURCE:
Dried leaves of erythroxylon coca (Bolivian variety) Erythroxylon truxillense (Peruvian
variety)
Family: erythroxylaceae
GEOGRAPHICAL SOURCE: Bolivia, Peru
Morphology:
Peruvian leaves are pale green, fragile, thin, and elliptical in shape
Bolivian leaves are greenish brown, oval in a shape with a prominent mid rib
 Collenchyma above & below mid rib
 Xylem surrounded by phloem & pericyclic fibres
 Paracytic stomata
Chemistry:
Cocaine, cinnamoyl cocaine, tropocaine, benzoylecgonine
Extraction:
The leaf powder is basified with lime & extracted using an organic solvent
The free bases are converted to their hydrohlorides by using HCl
Due to this procedure cocaine liberates ecgonine, methanol & benzoic acid whereas cinnamoyl
cocaine generates ecgonine, methanol & cinnamic acid
The ecgonine thus obtained is used to synthesize cocaine by treating it with benzoic anhydride,
methyl iodide, and methanol & sodium methoxide
Use:
Local anaesthetic
Chemical Test:
Drug powder when heated with concentrated H2SO4 gives a typical odour of methyl benzoate
QUINAZOLINE ALKALOIDS
VASAKA LEAF / ADULSA
BIOLOGICAL SOURCE: dried & fresh leaves of adhatoda vasica

Family: acanthaceae
Morphology:
Leaves are dark green, lanceolate in shape, have a crenate margin with a characteristic odour
& bitter taste
Chemistry:
Vasicine, vasicinone & adhatodic acid
Uses:
Vasicine is an expectorant. It gets oxidized to vasicinone which in an abortifacient in large
doses, otherwise a bronchodilator
PYRIDINE ALKALOIDS
LOBELIA HERB / INDIAN TOBACCO / ASTHMA WEED
BIOLOGICAL SOURCE: dried aerial parts of lobelia nicotianefolia

Family: campanulaceae
Morphology:
Leaves are sessile, large, dark green & possess an acrid taste
Chemistry:
Lobeline, lobelidine & isolobanine
Use:
Respiratory stimulant
Chemical Test:
1. Lobeline solution if heated gives typical odour of acetophenone
2. Lobeline in H2SO4 when treated with formaldehyde develops red colour
IMIDAZOLE ALKALOIDS
PILOCARPUS
BIOLOGICAL SOURCE: dried leaves of pilocarpus jaborandi, Pilocarpus microphyllus
Family: rutaceae
GEOGRAPHICAL SOURCE: south America
Morphology:
Leaves are greyish green with an asymmetrical base & possesses aromatic odour & bitter taste
Chemistry:
Contains pilocarpine, pseudopilocarpine, pilosine & limonene
Uses:
Antagonist to atropine, causes miosis, increases salivation & sweating
Chemical Test:
Pilocarpine solution when treated with H2SO4, H2O2, benzene & K2Cr2O4, the organic layer
appears bluish violet in colour whereas aqueous layer shows yellow colour
INDOLE ALKALOIDS
CALABAR BEANS
BIOLOGICAL SOURCE: dried type seeds of physostigma venenosum

Family: leguminosae
GEOGRAPHICAL SOURCE: Africa
Morphology:
Reddish brown in colour, hard, shiny & rough to touch
Chemistry:
Contains physostigmine, starch & proteins
Use:
Helps in contraction of pupil, retards respiration & causes bradycardia
OPIUM / POPPY PLANT

BIOLOGICAL SOURCE: dried latex obtained from capsules of papaver somniferum
Family: papaveraceae
GEOGRAPHICAL SOURCE: India (MP), turkey, Pakistan, Afghanistan
Collection:
 Collection is started when capsules change colour from dark green to yellowish green.
 Longitudinal incisions about 2mm deep are given on the capsules to exude the latex
 The latex is allowed to solidify overnight & later scraped off
 The process is repeated 4 times with a gap of 2 days

Morphology:
The dried latex is dark brown, extremely bitter to taste & has a strong odour
Chemistry:
Contains phenanthrene type of alkaloids such as morphine & codeine & benzyl isoquinoline
type of alkaloids such as papaverine & noscapine
These occur as salts of meconic acid
Use:
 Morphine is a narcotic analgesic & stimulant
 Codeine is an anti tussive
 Papverine is a smooth muscle relaxant
Chemical Test:
1. Aqueous solution of meconic acid shows a deep reddish purple colour with ferric chloride
2. Morphine when sprinkled with concentrated HNO3 shows an orange red colour. This is
not allowed by codeine
3. Morphine solution when treated with ferric chloride & potassium ferricyanide gives a
bluish green colour
4. Papaverine solution in HCl & potassium ferricyanide develops a lemon yellow colour
Varieties of opium:
Indian, Turkish, Persian, European, manipulated Persian & European
QUINOLINE AKALOIDS
CINCHONA BARK / JESUIT’S BARK / PERUVIAN BARK
BIOLOGICAL SOURCE:
Dried bark of cultivated trees of cinchona calisaya
Cinchona officinalis
Cinchona ledgeriana
Cinchona succirubra
Family: rubiaceae
GEOGRAPHICAL SOURCE: India, Bolivia, srilanka

Collection:
It is collected by coppicing method
Vertical incisions are made on branches, trunk of the tree & these incisions are connected by
horizontal circles
The bark is then stripped off & dried in sunlight & further by artificial heat (175 degree F)
The root bark is collected by uprooting trees & separating manually
Morphology:
Stem bark is rough with transverse fissures
Outer surface is grey & inner surface is pale yellowish brown to deep reddish brown
Root bark is curved, outer surface is scaly, outer & inner surface with same colour
 Cork cells are thin walled
 Cortex has phloem fibres
 Medullary rays with radially arranged cells
 Idioblast of calcium oxalate is a specific characteristic
 Starch grains in parechymatous tissues
 Stone cells rarely present
Chemistry:
Contains quinine, quinidine, cinchonine & cinchonidine
Also contains quinic acid & cinchotannic acid
Chemical Test:
1. On heating the drug in a dry test tube with glacial acetic acid, purple vapours are produced
2. Thalleoquin test: drug + bromine water + dilute ammonia gives an emerald green colour
3. Drug when treated with quinidine solution gives a white precipitate with silver nitrate
which is soluble in nitric acid
Uses:
Anti-malarial, anti-pyretic, quinine is used in arrhythmias against atrial fibrillation

ISOQUINOLINE ALKALOIDS
IPECAC
BIOLOGICAL SOURCE:
Dried roots of cephalis ipecacuanha (Brazilian / Rio), Cephalis acuminata (panama / Cartagena)
Family: rubiaceae
GEOGRAPHICAL SOURCE: Brazil, panama
Morphology:
Brazilian ipecac is dark brick red as compared to greyish brown panama ipecae
Both possess faint odour & bitter taste
Chemistry:
Brazilian – emetine: cephalin ratio is 4:1
Panama – emetine: cephalin ratio is 1:1
Uses:
Expectorant in mild doses & as an emetic in large doses
Emetine also possesses anti protozoal activity
Chemical Test:
1. Emetine shows a bright green colour with H2SO4 & molybdic acid
2. Emetine when shaken with water & small amount of HCl, filtered & to the filtrate potassium
chlorate is added gives a yellow colour changing to red
PYRIDINE- PIPERIDINE ALKALOIDS

TOBACCO
BIOLOGICAL SOURCE: dried leaves of nicotiana tabacum
Family: solanaceae
GEOGRAPHICAL SOURCE: India, France
Morphology:
Leaves are large, green with a dentate margin
It has a characteristic strong odour & bitter taste
Chemistry:
Nicotine, nornicotine & anabasine
Use:
Stimulant
PROTO ALKALOIDS
EPHEDRA / MA HUANG
BIOLOGICAL SOURCE: dried stem of ephedra gerardiana
Family: ephedreaceae / gnetaceae
GEOGRAPHICAL SOURCE: china, Pakistan
Morphology:
Greyish green, thin, cylindrical stem bearing scaly leaves & internodes
No typical odour but has a bitter taste
Chemistry:
Contains amino alkaloids like ephedrine, norephedrine & pseudo ephedrine
Uses:
Sympathomimetic & bronchodilator
Chemical Test:
Aqueous solution of ephedrine shows a violet colour when treated with dilute HCl & CuSO4
followed by dilute NaOH
COLCHICUM / AUTUMN CROCUS

BIOLOGICAL SOURCE: dried seeds & corms of colchicum luteum
Family: liliaceae
GEOGRAPHICAL SOURCE: Europe
Morphology:
Seeds are hard, reddish brown, rough to touch whereas corms are yellowish in colour with a
longitudinal groove & bitter to taste
Chemistry:
Contains amino alkaloid colchicine & demecolchicine

Uses:
Rheumatism, treatment of gout, anti-tumour activity & polyploidy
ACONITE / BACHNAG
BIOLOGICAL SOURCE: dried roots of aconitum napellus
Family: ranunculaceae
GEOGRAPHICAL SOURCE: Germany, Spain
Morphology:
Roots are dark brown, longitudinally wrinkled & tapering towards one end
They have slight odour & taste
Chemistry:
Diterpene alkaloids such as aconitine, neopelline, neoline & small amount of ephedrine
Aconitine is an active constituent but if hydrolysed forms benzoyl aconine & aconine which
are less active
Uses:
Externally in neuralgia & sciatica
PSEUDO ALKALOIDS
COFFEE
BIOLOGICAL SOURCE: dried seeds of coffee Arabica
Family: rubiaceae
GEOGRAPHICAL SOURCE: southern part of India, Indonesia
Collection:
The unripe coffee fruit is dark green & is collected when it turns red
Each fruit has two locules containing one seed each
The seeds are separated, roasted because of which they develop a dark brown colour & a typical
odour
Chemistry:
Contains caffeine which is a salt of chlorogenic acid, volatile oil known as caffeol, enzymes &
other phenolic compounds
Uses:
Stimulant, diuretic (due to theophylline), & source of caffeine

Chemical Test:
1. Murexide test: caffeine when heated with HCl & potassium chlorate give a residue which
turns purple when exposed to ammonia vapours
2. Caffeine forms a white precipitate with tannin solution
TEA
BIOLOGICAL SOURCE: prepared leaves of thea sinensis
Family: theaceae
GEOGRAPHICAL SOURCE: India, srilanka
Collection:
The tea plant is a small green shrub wherein younger leaves are picked & allowed to undergo
fermentation
Polyphenol oxidase carries out oxidation to produce furfural & other phenolic compounds
The process imparts a dark brown or black colour & a typical odour of tea powder
For preparation of green tea, fresh leaves are dried & roasted in copper pans & finally powdered
Chemistry:
Contains caffeine, theophylline, theobromine, oxidase enzyme & tannins
Use:
Stimulant, diuretic, source of caffeine
Chemical Test:
Murexide test
KOLA NUTS / BISSY SEEDS

BIOLOGICAL SOURCE: seeds of cola nitida
GEOGRAPHICAL SOURCE: west Africa, Brazil
Morphology:
Seeds are Plano convex in shape & reddish brown with a bitter taste
Chemistry:
Contains caffeine, theobromine & a red pigment known as kola catechin
Use:
Stimulant
COCOA SEEDS
BIOLOGICAL SOURCE: seeds of theobroma cacao
Collection:
The fruits are ellipsoidal in shape with a white pulp & contain about 40 to 50 seeds
Fermentation is carried out in boxes for about 3 days at a temperature below 60 degree Celsius
The seeds acquire a different coulour, taste & odour
Seeds are then roasted to evaporate the water
It also facilitates removal of the seed coat
Seeds are then powdered to obtain cocoa powder
Chemistry:
Caffeine. Theobromine, other phenolic compounds
Use: Stimulant
STEROIDAL ALKALOIDS
KURCHI
BIOLOGICAL SOURCE: dried bark of holarrhena antidysenterica
Family: apocynaceae
Chemistry:
Steroidal alkaloid conessine & norconessine
Use:
Amoebic dysentery
ASHWAGANDHA
BIOLOGICAL SOURCE: dried roots of withania somnifera
Family: solanaceae
GEOGRAPHICAL SOURCE: India, Afghanistan
Morphology:
Roots are cylindrical, buff coloured, have a characteristic odour & are tasteless
Outermost layer of cork cells followed by cortex
Vascular bundle consists of phloem parenchyma & xylem blocking the pith
Chemistry:
2 types of chemical constituents

1. Steroidal lactones called withanolides like withaferine
2. Alkaloids like withanine, somniferine, anaferine
Also contains alcohols known as somnitol & somnirol
Uses:
Sedative, hypnotic, hypotensive & immunomodulatory
PYRAZOLINE ALKALOIDS
PEPPER
BIOLOGICAL SOURCE: dried fruits of piper nigrum
Family: piperaceae
GEOGRAPHICAL SOURCE: south India, Indonesia
Morphology:
Fruits are green when unripe but turn dark black after drying
The dried fruits are wrinkled with an aromatic odour & pungent taste
Chemistry:
Alkaloid piperine is responsible for pungent taste aong with piperetine, resins, volatile oils
containing limonene & pinen responsible for the odour
Uses:
Bronchitis & gonorrhoea
 DO OTHER TOPICS FROM BOOK C.K KOKATE
 DO MICROSCOPY FROM KHANDELWAL BOOK
 THE TABLES GIVEN IN C.K KOKATE ARE IMP FOR GPAT EXAM
 PREPARE WELL ALL THE TABLES GIVEN IN C.K. KOKATE BOOK

PHARMA-ROCKS IMPORTANT SYNONYMS
Synonyms
CARBOHYDRATES Vasaka Adulsa Product Animal
used
Indian gum Gum Arabic, Acacia Digitalis Pigeon
Guar gum Jaguar gum, Punarnava Hog weed Glycogen Cat
Gum karaya Ind. Tragacanth, Sterculia Colchicum Atumun seed Insulin inj. Rabbit
gum
Isabgol Ind. Psyllium, flea seed Lobelia Ind. Tobacco Oxytocin Chicken
Bael Bengal Quince Areca nut Betel nut Parathyroid Dog
Agar Japnese Isinglass, Pilocarpus Jaborandi Vasopressin Rat
vegetable gelatin
Carragenan Irish moss extract Aconite Wolfsbane root Posterior pitutary Chicken
Mokshood
Inulin Alant starch, Dehlia OILS Tubocurarine Rabbit
chloride
Locust bean Aroban, Carob gum, Arachis oil Peanut oil Chorionic Male rat
Ceratonia gonadotropin
Starch Amylum Chaulmogra oil Hydnocarpus oil, Cod liver oil Rachitic rat
Gynocardia oil
GLYCOSIDES Heparin sodium Sheep
Aloe Mussaber, Kumari Sesame oil Gingelly oil Benne oil Iron dextran inj. Microbial
cultures
Rhubarb Revandchini Corn oil Maize oil Antiseptics & Frog
disinfectants
Cascara Sacred bark chittem bark Mustard oil Sarson oil Diphthria toxoid Rat
Hypericum St. John wort, Millepertuis, Nemm oil Margosa oil Atropine Rabbit
goat weed
Digitalis Foxglove Cocca butter Theobroma oil Insulin Prod. Guinea pig
Digitalis latanata Woolly foxglove, Austrial Kokum butter Goa butter, Mango Elastomeric Guinea pig
digitalis steen oil closures
Thevetia Yellow oleander, Trumpet Hydrous wool Lanolin Fungicides and
flower, Luckey nut tree fat germicides
Urgenia Indian Jangli pyaj, Sea onion Lard Adeps
squill
Eur. squill White squill Carnauba wax Brazil wax
Dioscorea Yam Linseed Flaxseed
Liquorice Mulethi TERPENOIDS
Senega Rattlesnake root Chenopodium American wormseed
oil
Quilllia Panama wood, Soap bark Eucalyptous Dinkum
Gokhru Puncture vine Peppermint Colepermin
Bitter Almond Amygdala amara Dill Anethum
WildCherry Bark Virginian prune bark Cinnamon Kalmi Cinnamon,
Ceylon Cinnamon
Silymarin Marian Thistle, Milk Jatamansi Indian spike nard
Thistle, Our lady’s thistle
Ginkgo Maiden hair tree, kew tree Tulsi Sacred basil
Visnga Khella, Picktooth tree Kapur kachri Spiked ginger lily
Psoralea Bavchi Oil of Vetiver Khus oil
Canthrides Spanish flies Cummin Jira

Bearberry Busserole Gaultheria Betula
Picrorrhiza Kutcki Artemisia Santonica
Henna Lawsonia Arnica Leopard bane,
Mountain tobacco,
Wolf’s bare
TANNINS Hops Humulus
Myrobalan Harde Sausserea Kuth, Kostus
Black Catechu Kattha Acorus Bach, Ghoda vaj,
Sweet Flag
Pterocrpus Bijasal DITERPENOIDS
Nux vomica Crow fig Semen Strychni Taxus Yew, Talispatra
Physostigma Calabar bean Crocus Saffron
Rawolfia Sarpagandha RESINS
Vinca Periwinkle Guggul Scented Bdellium
Belladona Deadly Nightshade Asafoetida Devils dung
Hyscamous Henbane Coloycynth Bitter apple
Stramonium Thorn apple leaf Cannabis Ind. Hemp
Cinchona Jesuit bark, Peruvian Bark Male fern Filixmas, Aspidium
Ephedra Ma-huang Kaladana Pharbitis
Guggul Scented Bdellium
Name of the test Test for Result/examine
Dragendroffs test Alkaloids Reddish brown ppt

Mayers reagent Alkaloids Cream colour ppt
Wagenrs reagent Alkaloids Reddish brown ppt
Hagers reagent Alkaloids Yellow ppt
Tannic acid test Alkaloids Buff colour
Picnolic acid test Alkaloids Yellow colour
millions test amino acids White ppt
Ninhydrine test Amino acids Violet colour
Molischs test carbohydrates Purple to violet colour
Barfoeds test Carbohydrates Red cupric oxide
Selivanhoffs test Carbohydrate/ ketones Rose colour ex: fructose,honey
Pentose test Pentose/carbohydrates Red colour
osazone Carbohydrates Yellow colour
Thinone test Cellulose /lignin Blue/bluish violet
………………… Volatile oil+ Sudan III solution Red colour by globules
Saponification test Fats & fixed oils Partial neutralization of alkali
Shinoda test Flavoniods Pink scarlet, crimson red, green to blue
colour
Alkaline reagent test Flavonoids Yellow colour
Zinc hydrochloride Flavonoids Red colour
Borntragers test Anthraquinone glycosides Rose pink to red colour
Modified borntragers Anthraquinone glycosides Rose pink to red colour
test
………….. Anthraquinone glycosides+ Pink colour
methanolic magenisum acetate
……………………… Hydroxyl anthraquinone + KOH Red colour
Keddes test Cardiac glycosides Purple colour
Keller- killani test Cardiac glycosides Blue colour
Raymonds test Cardiac glycosides Violet colour
Legal test Cardiac glycosides Blood red colour
Balijets test Cardiac glycosides Orange colour
Froth formation test Saponin glycosides Stable foam is formed
Haemolysis test Saponin glycosides Red supernatant
Gold beaters skin Tannins Brown/black colour
Ferric chloride test Tannins Green colour
Phenazone test Tannins Bulky ppt is formed
Gelatin test Tannins Ppt formed
Test for catechin Tannins Pink to phlorong luminol
Test for chlorogenic acid Tannins Green colour
Liberman burchard test Steroids and triterpenoids Green steriods,
deep red colour triterpinoids
Salkowski test Steroids, Red colour
Salkowski test triterpinoids Yellow coloured

Sulfur powder test Steroids,& triterpinoids Sinks of steroids & triterpinoids
Fehling solution A & B Carbohydrates Brick red
Identification test for enzymes
Papin +aqueous kmno4 solution …………………………decolourises
Esbachs for protein
Enrichs test for urobilinogen in urine
Kavous for indole
Millions test for protein estimation

PHARMAROCKS: THE WAY OF SUCCESS IMPORATNT DRUGS FROM PHARMACOGNOSY
Laxatives
Plant Name Biological name/ Synonym(s) Other names Part(s) Used Constituents Indications / Use
purgative (causes
Aloe barbadensis, Mill. griping),
A. Indica, Royle. Curacao Aloe, gel—topically
glyburide, anthraquinone
A. Littoralis, Koening Barbados Aloe, emollient, anti-
Aloe Juice glycosides – aloin,
A. Vera, Tourn. Ex Linn. Indian Aloe, inflammatory,
acemannan.
(Liliaceae; Agavaceae) Jaffarabad Aloe, antimicrobial - used
Kummari for wound healing,
sunburn.
chrysophan, chrysophanic
Rheum officinale, Baill. purgative, astringent,
acid, emodin, aporetin,
Rheum Palmatum, Linn. Rhizome, aperient. used for
Rhubarb Rhubarb phæoretin, erythroretin,
(Polygonaceae) root constipation and
rheumic acid, and
atonic dyspepsia
rheotannic acid
essential oils with alpha-
Blond Psyllium, pinene, dipentene, linalool,
Indian Plantago, cineol, methyl salicylate,
Plantago ovata, Forsk. Ispagol, Seed, decyl aldehyde, eugenol, seed -astringent.
Ispaghula
(Plantaginaceae) Pale Psyllium, husk anisaldehyde, bergapten, seed coat -demulcent.
Spogel indole, salicylic and
benzoic acids as major
constituents.
contains rhein, aloe-
purgative (free from
emodin, kaempferol,
Alexandrian Senna, astringent action of
isormamnetin, both free
Cassia senna, Linn. Cassia acutifolia rhubarb type herbs,
and as glucosides,
Cassia angustifolia, Vahl. Delite, but causes gripe),
Fruit (pod), together with mycricyl
Senna (Leguminosae) Khartoum Senna used in compounds
leaves alcohol the purgative
Indian Senna, for treating
principles are largely
Tinnevelly Senna biliousness, distention
attributed to anthraquinone
of stomach, vomiting
derivatives and their
and hiccups.
glucosides.
MR. AMAR M. RAVAL +91 9016312020 1 EMAIL ID: Pharmarocks77@gmail.com

Cardiotonics
Digitalis lanata, Ehrh. cardiac stimulant
cardiac glycosides found
Digitalis Digitalis purpurea, Ehrh. Grecian Foxglove Leaves diuretic
throught entire plant
( Scrophulariaceae) emetic
quinazoline alkaloids -
vasicoline, adhatodine, cold. cough,
Adhatoda zeylanica, Medic.
Malabarnut, vasicolinone and whooping-cough and
Adhatoda vasica, Nees. Leaves along
Adulsa Vasaka anisotine . vasicinol, chronic bronchitis and
(Acanthaceae ) with tender stem
Adulsa vasicinone, asthma as sedative-
deoxyvasicinone, expectorant
deoxyvasicine
Carminatives and GI regulators
contains volatile oil, stimulant, stomachic,
consisting mainly of delta- carminative,
Dhaanyaka, linalool, alpha-pinene and antispasmodic,
Coriandrum sativum, Linn. Kustumburu, terpinine. it also contains diuretic; also
Coriander Fruits
(Umbelliferae) Dhaanyeyaka, flavonoids, coumarins, hypoglycaemic and
Dhanika phthalides and phenolic anti-inflammatory.
acids (including caffeic and oil—bactericidal
chlorogenic) and larvicidal.
fennel seed contain volatile carminative,
Mishreyaa, oils anethole, among stomachic,
Mishi, others fenchone and antispasmodic,
Foeniculum vulgare, Mill.
Fennel Madhurikaa, Fruits methylchavicol), emmenagogue,
(Umbelliferae)
Madhuraa, flavonoids, coumarins galactagogue, anti-
Shatapushpaa (including bergapten) and inflammatory,
sterols diuretic.
Trachyspermum ammi, Linn. Ammi, Fruits the seeds contain a fruits—carminative,
Ajowan Carum copticum, Benth. Lovage, Leaf juice phenolic glucoside, antispasmodic,
(Umbelliferae) Carum, Root principal constituents of the anticholerin,
Ajowan, ajowan oil are the phenols, antidiarrhoeal,

Yavaani mainly thymol and some bechic, stimulant.
carvacrol. leaf juice—
anthelmintic.
root— carminative,
diuretic, febrifuge.
seeds yield an essential oil seed - carminative
the major constituents are, antiemetic, stomachic,
Elettaria cardamomum, Lesser Cardamom ,
1,8-cineole and alpha- orexigenic, anti-gripe,
Cardamom Maton Elaa, Seed
terpinylacetate, with antiasthmatic, bechic,
(Zingiberaceae) Sukshmailaa.
limonene, alpha-terpineol, oil - antispasmodic,
sabinene and linalool. antiseptic.
contains an
essential oil containing
monoterpenes, mainly antiemetic,
Fresh rhizome— geranial and neral; antiflatulent,
Aardraka, sesquiterpenes mainly hypocholesterolaemic,
Aadrikaa, beta-sesquiphellandrene, anti-inflammatory,
Zingiber officinale, Roscoe.
Shrngibera. betabisabolene; antispasmodic,
Ginger (Zingiberaceae) Rhizome
Dried rhizome— aromatic curcumene and expectorant,
Shunthi, alphazingiberene; circulatory stimulant,
Naagara. pungent principles, diaphoretic, increases
consisting of gingerols, bioavailability of
shogaols and related prescription drugs.
phenolic ketone
derivatives.
stimulant, carminative,
the fruit yielded piperine,
diuretic, anticholerin,
piperatine and piperidine;
Black Pepper , sialagogue, bechic,
Piper nigrum, Linn. amides, piperyline,
Black pepper Maricha, Fruits antiasthmatic. used in
(Piperaceae) piperoleins a and b,
Vellaja fevers, dyspepsia,
and n-isobutyl- cicosa-
flatulence, indigestion,
trans-2-trans-4-dienamide.
and as mucous

membrane and
gastro-intestinal
stimulant.
ferula foetida contains:
resins consisting of
asaresionotannols
and their esters;
farnesiferols,
Ferula assafoetida Linn. Oleo gum resin olea-gum-resin—
Asafetida, Asant, ferulic acid and other acids;
Ferula rubricaulis Boiss. obtained by stimulates the
Devil’s Dung, Gum gum; volatile oil, major
Asafoetida Ferula foetida Bunge. incising the intestinal and
Asafetida constituent being sec-
(Apiaceae / Umbelliferae) living rhizomes respiratory tracts and
propenylisobutyl
and roots. the nervous system.
disulphide; sulphated
terpenes, pinene, cadinene
and vanillin;
sesquiterpenoid
coumarins.
nutmeg is used in
contains anti-inflammatory
flatulency, diarrhoea,
principle,
Nutmeg, Mace, nausea and vomiting.
Myristica fragrans Houtt. Dried seed and and licarin-b and dehydro
Nutmeg Jaatiphala, mace is used in
(Myristicaceae) Aril diisoeugenol,
Jaatishasya. rheumatism, chronic
eugenol and isoeugenol,
bowel complaints and
myristicin.
asthma.
Ceylon Cinnamon,
Cinnamomum verum leaf—carminative,
Cinnamomum zeylanicum Bl. J.S. Presl., True antidiarrhoeal,
Cinnamomum loureirii Nees. Cinnamon cinnamaldehyde, alpha- spasmolytic,
Cinnamon Cinnamomum burmanii Cinnamomum Inner bark and beta-pinene, pcymene antirheumatic,
(Nees) Bl. obtusifolium Nees and limonene, linalool hypoglycaemic.
(Lauraceae) var.loureirii Perr. & Eb., essential
Saigon Cassia, Saigon oil—fungicidal.
Cinnamon

Batavia Cassia,
Batavia Cinnamon,
Padang-Cassia,
Panang Cinnamon
carminative,
antiinflammatory,
antibacterial.
Syzygium aromaticum (Linn.) Flower buds—

Merr. & Perry. antiemetic, stimulant,
eugenin,
Caryophyllus aromaticus Lavanga, carminative, used in
triterpene acids,
Linn., Devakusum, dyspepsia, gastric
crategolic acid,
Eugenia aromatica (Linn.) Devapushpa, Clove (dried irritation.
Clove steroid glucosides.
Baill., Shrisangya, flowerbud)
Eugenol a major
Eugenia caryophyllata Shriprasuunaka oil—
component of the oil, is
Thunb., employed as a local
antibacterial.
(Myrtaceae) analgesic for
hypersensitive
dentlines and carious
cavaties; internally
as a carminative and
antispasmodic
Astringent
contains
tannins ─ mainly catechins
and catechu tannic acid, demulcent,
Pale Catechu, extract of the
Uncaria gambier, Roxb. indole alkaloids ─including emollient,
Catechu Gambier, leaves and
(Rubiaceae) gambirine, gambiridine; expectorant,
Khadira shoots
flavonoids ─ quercetin; diuretic,
pigments and intestinal astringent.
gambirfluorescin.

Drugs acting on Nervous System

Indian Henbane, Sedative. Narcotic
tropane alkaloids ─
Hyoscyamus niger, Linn. Black Henbane, Leaves and drug. Used for
Hyoscymus hyoscyamine,
(Solanaceae) Paarsika-yavaani, flowering tops convulsions. Action
and hyoscine.
Ajwaayin. similar to Belladonna
atropine, (dl-hyoscyamine),
l- scopalomine (tropane antispasmodic,
alkaloid) parasympathetic,
Belladonna, (atropine is converted to l- depressant,
Atropa belladonna, Auct. fruits,
Belladonna Deadly Nightshade, hyoscyamine by an vasoconstrictor,
(Solanaceae) leaves
Suuchi enzyme when the plant is smooth muscle
dry, therefore the plant is inhibitor,
more active when dry) bronchodilator.
starch, sugar, mucilage
narcotic, sedative,
antileprotic,
anti-inflammatory.
extremely poisonous.
Aconitum ferox Wall. ex Ser. Aconitum, (roots possess
aconitia,
Aconite Aconitum napellus Linn. Indian aconite, tuber depressant
aconitine or nepalline
(Ranunculaceae) Monkshood activity, but after
mitigation in
cow’s milk for 2–3
days, they exhibit
stimulant activity.)
Withania ashwagandha, Kaul. Winter Cherry, alkaloids ─ withanine, root—used as an
Ashwa-
(cultivated variety) Ashwagandhaa, root withananine, antiinflammatory
gandha
W. somnifera Linn. Hayagandhaa, withananinine, drug for swellings,
(Solanaceae) Ashwakanda, pseudo-withanine, tumours, scrofula and

Gandharvagandhaa. somnine, rheumatism; and as a
somniferine, sedative and hypnotic
somniferinine. in anxiety neurosis.
steroidal lactones ─
withanolide,
Ephedra sinica, Stapf.
Cao Ma Huang, E. arial parts: diaphoretic
E. Equisetina, Bunge.
Mahuang Liu, arial: stimulant
E. Intermedia, Shrenk. ex
Ephedra (and some alkaloids ephedrine, astringent
Ephedra Meyer.
other herbs) has also phytosterols. decongestant
E. Gerardiana, Wallich. ex
been referred to as root: ephedrine, tannin, expectorant diuretic
Meyer.
‘herbal ecstasy saponin, flavone, oil root: diaphoretic
(Ephedraceae)
opium is obsolete
isoquinoline alkaloids ─
Opium Poppy, as a drug. narcotic,
morphine, narcotine,
Papaver somniferum, Linn. Ahiphena, dried poppy sedative, hypnotic,
Opium codeine, papaverine and
(Papaveraceae) Aaphuuka, juice analgesic, sudorific,
thebaine.
Afyum. anodyne,
antispasmodic.
hallucinogenic,
cannabis yields 421 hypnotic, sedative,
Hemp,
chemicals of various analgesic,
Indian Hemp,
classes—cannabinoids, antiinflammatory,
Vijayaa,
Cannabis sativa, Linn. dried leaves or cannabispirans, hemp derivatives
Cannabis Bhangaa,
(Cannabinaceae) juice and many alkaloids, are suggested for
Maadani,
of which treating glaucoma
Maatulaani,
δ -9- tetrahydrocannabinol and as an antiemetic
Indraasana.
(thc) is important. in cancer
chemotherapy.
strychnine, brucine,
Strychnos Nux-vomica, Linn. bitter stomachic and
Nux vomica Semina Strychni seeds caffeotannic acid, igasuric
(Loganiacoe) tonic
acid, loganin
Antihypertensive
indole alkaloids (more than
50 alkaloids identified,
reserpine - best known)
Rauvolfia serpentine, Benth. Snake root, anti-hypertensive alkaloids
Rauvolfia root anti-arrhythmic
(Apocynaceae) Sarpgandha (alseroxylone, corganthine,
anti-hypertensive
voxinil, rescinamine)
anti-arrhythmic alkaloids
─ ajmaline
Antitussive
Plant Name Biological name/ Synonym(s) Other names Part(s) used Constituents Indications / use
quinazoline alkaloids -
vasicoline, adhatodine, cold. cough,
Adhatoda zeylanica, Medic
Malabarnut, vasicolinone and whooping-cough and
Adhatoda vasica, Nees. leaves along
Vasaka Vasaka anisotine . vasicinol, chronic bronchitis and
(Acanthaceae ) with tender stem
Adulsa vasicinone, asthma as sedative-
deoxyvasicinone, expectorant
deoxyvasicine
toluene, benzylic benzoate,
Toluifera Balsamum, Linn. balsam of the benzylic cinnamate,
Tolu Balsam Balsamum Tolutanum expectorant
(Leguminosae) plant benzoic acid, cinnamic
acid, resins
Major components of the leaf— expectorant,
essential oil are eugenol, carminative,
carvacrol, nerol and stomachic,
eugenolmethylether. antispasmodic,
Holy Basil,
Leaves have been antiasthmatic,
Ocimum Sanctum, Linn. Sacred Basil,
Tulsi seed, leaves reported to contain ursolic antirheumatic,
(Labiatae) Tulsi,
acid, apigenin, stimulant,
Surasa
luteolin, apigenin-7-O- hepatoprotective,
glucuronide, antipyretic and
luteolin-7-O-glucuronide, diaphoretic.
orientin and molludistin. seed— used in

genitourinary
diseases.
Antirhumatics
Plant Name Biological name Synonym(s) part(s) used constituents indications / use
Commiphora mukul, Hooker. Indian Bdellium, gum ─ resin anti-cholesterol,
Guggul guggolestrones E, Z.
(Burseraceae) Guggulu exudes antirhumatic
seed and the antirhumatic,
Colchicum autumnale, Linn.
Colchicum corn of colchicine as emetic in
(Liliaceae)
colchicum poisioning
Antitumour
anticancer, circulatory
indole alkaloids stimulant
Vinca major, Linn. whole plant
Vinca Periwinkle, amaranth (vincamine, cinblastine) (increases blood flow
(Apocynaceae) extract
tannins to the brain)
hypotensive
Antileprotics
fixed oil, 25-50 % contains
palmitin, linolein, but chiefly
Chaulmoogra
Taraktogenos. glycerides of two fatty
oil / Oleum Taraktogenos Kurzii, King.
Chaulmoogra. Seed oil acids—chaulmoogric, cho, leprosy
Chaulmoogra (Hydnocarpus)
Chaulmoogra. and hydnocarpic, cho,
e
starch, proteins, tannin,
coloring matter
Antidiabetics
kino-tannic acid,
diabetes, diarrhea,
Pterocarpus Marsupium, kino-red, kinoin,
Gummi (Resina) Kino, pyrosis, menorrhagia,
Pterocarpous Rozburgh. bark juice pyrocatechin
Vengay, Bastard dysentery, leucorrhea,
(Papilionaceae; Fabaceae) (pyrocatechuic acid,
ulcers,
catechol),
MR. AMAR M. RAVAL +91 9016312020 EMAIL ID: Pharmarocks77@gmail.com
9
leaf—antidiabetic.
stimulates
the heart and
circulatory
system, activates the
Australian Cow Plant, uterus. used
Ipecacuanha (Indian). in parageusia and
Gymnema Gymnema sylvestre B. Br. leaves or whole gymnemagenin,
Meshashringi, furunculosis.
sylvestre (Asclepiadaceae) plant gymnemic acids
Meshavishaanikaa,
whole plant—diuretic,
antibilious.
root—
emetic, expectorant,
astringent,
stomachic.
Diuretics
plant contains saponins,
which on hydrolysis yield fruits—diuretic,
sapogenins—diosgenin, demulcent,
gitogenin, chlorogenin, anti-inflammatory,
ruscogenin, anabolic,
Gokshura, 25d-spirosta-3, 5-diene, spasmolytic, muscle
Gokshuraka, among others. flavonoids— relaxant,
fruit,
Tribulus terrestris, Linn. Kshudra (Laghu) rutin, quercetin, hypotensive,
Gokhru leaves,
(Zygophyllaceae) Gokharu, kaempferol, kaempferol-3- hypoglycaemic.
root.
Shvadamshtraa, glucoside and-rutinoside,
Swaadu-kantaka and tribuloside have leaf—diuretic,
been isolated fromthe haemostatic.
leaves and fruits.
theseeds contain carboline root—stomachic,
alkaloids— diuretic.
harmane and harmine.

harmol is also reported

from the herb.
diuretic,
anti-inflammatory,
antiarthritic,
spasmolytic,
antibacterial
Horse-purslane, (used for inflammatory
Hogweed, xanthone, renal diseases,
Boerhavia diffusa, Linn. Rakta-punarnavaa, beta-ecdysone. nephrotic syndrome,
Punarnava whole plant
(Nyctaginaceae) Punarnavaa, flavonoid, in cases of ascites
Katthilla, arbinofuranoside resulting from
Shophaghni. early cirrhosis of liver
and chronic
peritonitis, dropsy
associated with
chronic bright’s
diseases
Antidysenterics
emetine, cephaeline,
Cephaelis ipecacuanha, cephaelic acid,
antidysenterics,
Ipecacuanha A. Richard Ipecacuanha. Ipecac dried root epecacuanhic acid, tannic
emetic
(Rubiacae) acid, volatile oil, starch,
gum
Antiseptic and disinfectant
benzaldehyde, vanillin
resinous
(1 %), phenylpropyl
Styrax benzoin, Dryander. exudates antiseptic and
Benzoin Sumatra benzoin cinnamate, styrol, and
(Styraceoe) obtained by disinfectant
styracin, cinnamic acid,
injury to the tree
benzoic acid
Myrrh Commiphora myrrha Nees. African Myrrh, oleo-gum-resin the gum contains acidic antiseptic and
(Burseraceae) Arabian Myrrh, polysaccharides, volatile oil disinfectant

Balsamodendron including other
Myrrha, constituents, eugenol,
Bitter Myrrh, heerabolene,
Commiphora, monoterpenes and
furanosequiterpenes.
amorphous resin, a
Neem, leaves, crystalline, bitter alkaloid insect repellant, bitter
Melia Azadirachta, Linn.
Neem Limb, bark, (margosine), margosia tonic, antiseptic and
(Meliaceoe)
Nila seed oil. acid, a crystalline disinfectant
substance and tannin
contains volatile oil 5-10%,
antiseptic and
turmerones which are
disinfectant,
Curcuma Longa, Roxb Turmeric, haridra, the dried sesquiterpene, ketones,
Curcuma stomachic, aromatic,
(Zingiberaceae) haldi, halad. rhizome Curcumin, Curcuminoids,
stimulant; dyspepsia,
bitter principles, sugars,
flatulence
starch, resin.
Antimalarial
quinine, quinidine,
Calisaya Weddell, Linn. Quills or in
Cinchona bark, cinchonine, cinchonidine,
Cinchona Cinchona officinalis, Linn. curved pieces of malaria
Jesuit bark. quinamine, quinic acid,
(Rubiaceae) bark
quinovic acid
Oxytocics
Claviceps purpurea, alkaloids (ergotamine) oxytocic,

Ergot (Clavicititaceae) Rye ergot dried sclerotium ergotic/ergotinic acid, hemostatic,
sclerotic motor excitant
Vitamins
Emblica officinalis, Gaertn. Phyllanthus emblica, vitamin C (ascorbic acid), antianaemic, anabolic,
Amla Fruit pericarp
(Euphorbiaceae) Aaamalaki, Aaamalaka zeatin, phyllembin, antiemetic, bechic,
minerals and amino acids astringent,

antihaemorrhagic.
Enzymes
digestive in dyspepsia
stomachic,
carminative, diuretic,
Carica Papaya, Linn. galactagogue. useful
Papaya Papain or Papayotin papain enzyme plant enzyme
(Caricaceae) in bleeding piles,
haemoptysis,
dysentery and chronic
diarrhoea.
Perfumes and Flavoring Agents
menthol, menthone,
digestive, carminative,
pulegone, enthofuran,1,8-
chloretic,
cineole, menthyl acetate,
antispasmodic,
isomenthone, the leaves
diuretic,
contain flavonoid
antiemetic, mild
Pudinaa, steam distilled glycosides, eriocitrin,
Peppermint Mentha piperata, Linn. sedative, diaphoretic,
Peppermint, Brandy volatile oil of the luteolin 7-0-rutinoside,
oil (Labiatae; Lamiaceae) antiseptic, antiviral,
Mint plant hesperidin, isorhoifolin,
used in
diosmin, eriodictyol 7-O-
many mixtures of
glucoside and narirutin,
indigestion and
besides rosmarinic acid,
colic and cough and
azulenes, cholene,
cold remedies.
carotenes.
antiscorbutic,
volatile oil (about 2.5% of
carminative,
Jambira, Jambh, the peel) consists of about
stomachic,
Citrus limon, Linn. Jambhir, 75% limonene,
Lemon oil peel oil antihistaminic,
(Rutaceae) Jaamphal, Nimbu, alpha-and beta-pinenes,
antibacterial. used
Nimbuka, neebu alpha-terpinene, citral,
during coughs,
hesperidin, rutin.
colds, influenza and
onset of fever
Santalum album, Linn. Chandan, Sandal, Heartwood of phenols - santalol, borneol, aromatic therapy,
Sandalwood
( Santalaecae) Sandalwood the plant alcohols - α-norisoborneol perfumary
Miscellaneous
glycyrrhizin 2-8%,
Gan Cao demulcent,
triterpene saponin,
(root/rhizome), expectorant,
glycyrrhetinic acid,
Glycyrrhiza glabra L. antiallergic, anti-
Glycyrrhiza glabra, Linn. root, isoflavonoids, chalcones,
Liquorice Var. Glabra, G.glabra inflammatory,
(Papilionaceae, Fabaceae) stolon coumarins, triterpenoids
L. Subsp. Glandulifera spasmolytic, mild
and sterols, lignans, amino
(Waldst. & Kit.) Ponert, laxative, antistress,
acids, amines, gums and
Licorice antidepressive
volatile oils
disulphide compounds
Ajo, Allium,
allicin (via allinase) anti-microbial
Allium sativum, Linn. Lashuna, Rasona, bulb
Garlic alliin, diallyl disulphide, hypotensive
(Liliaceae, Alliaceae) Yavaneshta, (clove)
lipids, mucilage, albumin hypolipidemic
Ugragandha
vitamins A, B, C, E.
glycosidal bitter
principle, kutkin found to be
a mixture of two iridoid
in jaundice,
Picrorhiza kurroa, glycosides, picroside
Katukaa, Katurohini, intermittent fever,
Picrorhiza Royle ex Benth root i and kutkoside also
Kutki. dyspnoea and
(Scrophulariaceae) obtained were D-mannitol,
skin diseases
kutkiol, kutkisterol
and a ketone (identical with
apocynin).
tubers—used for
ulcer, to
Dioscorea anguina, Roxb. dioscorine , furanoid
Wild yam, Colic-root, kill worms in wounds.
Dioscorea Dioscorea bulbifera, Linn. tubers norditerpenes, contain
Dioscorea villosa plant parts—
(Dioscoreaceae) nearly 83% starch
used in whitlow, sores,
boils.
inflammation of
mucous membranes
fixed oil 35-40%, tannin, of respiratory,
Linum usitatissimum, Linn. Flaxseed, Flax, Lint-
Linseed ripe seed amygdalin, mucilage, oleic digestive, and urinary
(Linaceae) bells, Winter lien
acid, linoleic acid organs, renal and
vesical irritation,
catarrh, dysentery,
as galactagogue, for
disorders of female
saponins— genitourinary tract,
Indian asparagus ,
shatavarins I–IV. ulcer-healing agent,
Asparagus racemosus Willd. Shataavari, Shatmuuli,
Shatavari dried root shatavarin IV is a glycoside intestinal disinfectant
(Asparagaceae) Atirasaa, Bahusutaa,
of sarsasapogenin, and astringent in
Shatpadi, Shatviryaa
sitosterol etc. diarrhea, nervine tonic
and in sexual debility
for spermatogenesis
evolvine,
E. Angustifolius Roxb.
beta-sitosterol, stearic, brain tonic, an aid in
Shankh- Evolvulus alsinoides, Linn. Convolvulus alsinoides aqueous extract
oleic, linoleic conception, astringent,
pushpi (Convolvulaceae) L. Shankhphuli, of whole plant
acids, pentatriacontane antidysenteric.
Shivakrandi
and triacontane
an acrid, brown resin,
Pellitory, inulin, anacycline, sialogogue, stimulant,
Anacyclus Pyrethrum, Linn. Officinarum Hayne, isobutylamide, cordial, rubefacient,
Pyrethrum root
(Compositae) Aakallaka, Aakulakrit, inulin and a trace of insulin-dependent
Agragraahi essential diabetes mellitus
oil.
muscle relaxation in
dislocation,
Indian tobacco,
Nicotiana tabacum, Linn. nicotine strangulated hernia
Tobacco Taamraparna, herb
(Solanaceae ) and orchitis arthralgia,
Dhuumrapatraa
lumbago, rheumatism
and gout

PHARMAROCKS
GPAT -2016 BOOKLET
VITAMINS IMPORTANT INFORMATION
TABLE WISE NOTES
MR. AMAR M. RAVAL
CONTACT US +91 9016312020
FAT SOLUBLE VITAMINS (A D E K)
VITAMIN PHYSIOLOGIC FUNC. DEFICIENCY Toxicity U.S. RDA SOURCES
VITAMIN A  Proper night vision  Night blindness  Toxic in large amounts.  Adult: 3,000 IU  Liver, fish oil
(Retinol):  Formation & maintenance of  Keratinization of corneal  Loss of hair, joint pain,  Inf: 1,300 – 2,600  Butter, whole
Retin = Retina healthy epithelial tissue. epithelium  Xerophthalmia jaundice, L. bone thicken  Ped. prepn. must milk, egg yolk
ol = alcohol  Growth of skeletal / soft tissues  Keratinization of epithelium  In children: hyperstoses contain > 1,000 IU  Green & yellow
B-carotene  bone & teeth of skin / mucous membrane (bone hypertrophy)  Adult prepn. must vegetables
Retinol   Deficiency can be due to: leading to Infections  In adults & children: contain > 1,600 IU  Yellow fruits
11 cis retinol o Inadequate dietary intake  Faulty tooth formation. o Peeling of skin  No prepn. should (apricots)
o Poor absorption  Retarded growth contain > 10,000
o Headache, Nystagmus
o Inadequate hepatic  Loss of appetite
 1IU = 0.3  retinol,
conversion of B carotene o Lymph node enlarge 0.6  carotene
VITAMIN D:  Para-hormone (involved in Ca / P  In children: faulty bone o Calcification of soft 400 IU (children;  Fish oil / yeast
metabolism) formation & rickets (cranial tissues lungs / kidney pregnant or lactating
Formed in the body  Fortified or
women)
by skin exposure to  Absorption of Ca & P from GIT bones soften, bowed o Hyper-calcemia irradiated milk.
UV from sun or  Tubular reabsorption of Ca thighs & knock-knees) 1 IU vitamin D =  In few foods:
o Bone fragility.
lamp 0.025 g vitamin D2. cod liver oil, little
 Calcification of bones (Ca  In adults: osteomalasia & o  Digitalis tox. , MI
(CALCIFEROL) in milk, egg yolk
mobilization from bone to blood) hypo-parathyroidism.
VITAMIN E:  Related to action of Selenium  Hemolysis of RBCs  Safe in large doses  Adult: 5 - 10 IU  Vegetable oil.
Anti-sterility vitamin  Antioxidant (protects # peroxides  Anemia.  Increases vitamin  Seed oils.
(proven in rats) which can destroy RBCs &  Sterility in males. A absorption  Others: milk,
capillary walls)  Anti-oxidant eggs, meat &
 Habitual abortion in females
 Normal development of muscles fish.
 Muscular dystrophy
 Safe in large doses
VITAMIN K:  Blood clotting, necessary for  Hemorrhagic tendencies  o Inf: hemorrhagic  UNKNOWN  Green leafy
hepatic synthesis of prothrombin.  PT time. anemia, kernicterus,  Synthesized by vegetables,
(MENADIONE)
 Toxic in large amounts.  Xss oral AB  inhibits flora &  bilirubin. normal GIT flora  Cheese, egg
 Vitamin K deficiency. o In adults:  liver yolk, liver.
functn.  Jaundice.
WATER SOLUBLE VITAMINS (VITAMIN B-COMPLEX & VITAMIN C)
VITAMIN PHYSIOL. FUNCTIONS Deficiency Toxicity U.S. RDA SOURCES
THIAMINE  Coenzyme in carbohydrate  Results from eating white  Very safe; toxicity not Adults > 0.6 mg  Beef, liver, pork,
(B 1) metabolism (2 C atom wheat polished rice & marked. Infants > 0.4 mg fish, eggs.
metabolism getting rid of alcoholics Beriberi Uses:  Whole or
Anti-beriberi pyruvic).  GI: Anorexia,  HCl Beriberi enriched grains.
factor
 CNS: Fatigue, Mental Periph neuritis in DM  Yeast
(Oral / IM / SC) Disorders, Periph neuritis, Neuralgia  Vitamin B1 is
 CV: Card. failure / LVH, TC Mental Disorders thermolabile.
RIBOFLAVIN  Coenzyme in protein  Wound aggravation Adults > 1.0 mg  Milk, liver,
(B 2) metabolism (proton carrier).  Cheilosis (cracks at corners Infants > 0.6 mg kidney
The yellow green  Deficiency  tissue of mouth).  Never given alone  Enriched cereals
florescent pigment in inflammation. (def. occurs in  Glossitis, eye irritation. but with other B  Absorbed from
milk conjunctn. with other B vit.) vit. (Oral, IM, SC) upper GIT
 Seborrheic dermatitis.
NIACIN  Coenzyme in tissue oxidation  Pellagra characterized by  Vasodilatatn, flushing Adults: > 6 - 45 mg  Meats
(B 3) as H+ carrier  energy (ATP scaly dermatitis,  Hepatotoxicity Infants > 4 mg  Peanuts, beans,
productn in respiratory chain). photosensitivity & fatal (niacin equivalent) peas
As nicotinic acid or  GI irritatn/ ulceration
 Metabolism of Fat, protein, effects on CNS 60 mg tryptophan =
nicotinamide (when  Enriched grains.
glucose.  Weakness, lassitude  Hyperuricemia 1 mg nicotinic acid
vasodilatation is
contraindicated we  Uses: ttt of pellagra.  Anorexia, indigestion. B3 & B2 are closely
 Glucose intolerance interrelated in cell
can use nicotinamide
 Nicot. a (not nicotinamide)  CNS: neuritis, confusion, (hyperglycemia) metabolism. If one is
instead of nicotinic a
> 3 gm / day, hypocholest. apathy, schizophrenia. deficient the other is.
PYRIDOXINE  Coenzyme in amino acid  Anemia (hypo chromic, B6 is contraindicated wit L- 2 mg (Pregnancy &  Wheat, corn, yeast
(B 6) metabolism (in decarboxylation microcytic). dopa (Why) estrogen/progest OC
 Meat, liver, Kidney
& transamination)  B6  additional B6)
Pyridoxal is more  CNS: epileptic convulsions,  GIT flora  B6 but
stable than  Production of GABA (a peripheral neuritis. INH, hydralazine &
significance not
pyridoxine neurotransmitter inhibitor that penicillamine deplete
determined
prevents convulsions) tryptophan  B6 def.
VITAMIN PHYSIOLOGIC FUNC. Deficiency Toxicity U.S. RDA SOURCES
PANTOTHENIC  Coenzyme in overall body Contributes to:  Locally to aid wound GIT flora syn. a  Liver, kidney
metabolism healing. considerable amount
ACID (B5)  Amino acid activation  Yeast, egg yolk
 IM to aid motility of the + wide spread in nat.
Found throughout  Converted to Co-A (Ac Ch  Formation of Cholesterol  Skimmed milk.
intestine after surgical op sources  def. not
body tissues synthesis & fatty a metabolism)
 Excretion of drugs (post-op paralytic ileus. common  Leafy vegetable
.
FOLIC ACID  Important in cell growth &  Megaloplasic anemia  Not toxic by oral route 50 ug  Liver, kidney
blood forming factors.  Sprue (GIT disease  Pern. anemia (doesn’t  Green leafy
 Essential for synth. of purine & characterized by severe control neurologic sym) vegetables
pyrimidine nucleotides diarrhea).  Megaloblastic anemia.  Asparagus.
 Sprue treatment.
COBOLAMINE  Coenzyme in protein synthesis  Pernicious anemia 6 ug.  Liver, meat, egg.
(B12)  Formation of red blood cells.  Sprue treatment + folic a milk, cheese.
BIOTIN  Coenzyme in CO2 reactions in  Undetermined.  Synthesized by GIT flora “micronutrient” bec  Egg yolk,
energy metabolism. or with ingested food (nat. minute traces 
 Liver, kidney.
def. unknown) metabolic task
 Involved in fatty a synthesis &  Tomato, yeast
in carboxylation reactns.  Large amounts of egg
white  deficiency.
CHOLINE  Essential for synthesis of   Synth. in body from

phosphatidyl-choline amino acid methionine
involved in lipid transport &
acetylcholine synthesis
VITAMIN C  Building & maintaining  Scurvy *  Increased stone Adult > 150 mg Citrus fruits,
collagen, cartilage, bone matrix formation in UT. Child > 20 mg tomatoes, green &
(ASCORBIC  Megahemoglobinemia (bec
& connective tissue. yellow vegetables
ACID) of its reducing properties)  Diarrhea
(cabbage, potatoes)
 Wound healing, tissue  Wound healing, tissue Women have
 10 gm daily of vit C & strawberries.
 GIT absorption of iron formation (cementing
followed by rapid higher vitamin C
 Redox reactions in the body  connective tissue)
withdrawal  frank levels than men.
Cellular respiration  Fever, infections  stored
symptoms of scurvy. Smoking  vitamin
vitamin C
 Stress reactions  Scurvy develops in C levels in blood.
newborns to mothers
 Growth period.
who suddenly stop large
 ttt of alcohol overdose 
daily doses of vitamin C.
stimulates alcohol
dehydrogenase
MEDICINAL CHEMISTRY NOTES MR. AMAR M. RAVAL
AMINOGLYCOSIDES
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modified
sugars. These are glycosides of amino sugars. Aglycone part in streptomycin is inositol
derivative streptidine that contains two guanido groups at 1 and 3-position of inositol.
Streptomycin is tri-acidic base on hydrolysis it produces streptidine and streptobiosamine.
Streptobiosamine further breaks in streptose and N-methyl glucosamine. Other
aminoglycosides like gentamicin, tobramycin, kanamycin, neomycin are 2-deoxy streptamine
derivatives.
Several aminoglycosides function as antibiotics that are effective against certain types of
bacteria. They include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin,
paromomycin, rhodostreptomycin, streptomycin, tobramycin, and apramycin.
NOMENCLATURE
Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the
suffix -mycin, whereas those that are derived from Micromonospora are named with the suffix -
micin.
This nomenclature system is not specific for aminoglycosides. For example, vancomycin is a
glycopeptide antibiotic and erythromycin, which is produced from the species
Saccharopolyspora erythraea (previously misclassified as Streptomyces) along with its synthetic
derivatives clarithromycin and azithromycin, is a macrolide.
NH
H2NH 2C
2-deoxy straptamine dererivatives
HO H2N
Streptidine NH HO
CH 2H2N
NH NH1 O H2N
2 O H2N
HO NH2
HOH2C 6 HO NH NH2
O NH R
H3C OH 3 O OH NH2
O OH O OH
NH 5 4 O NH2
HO HOH2C O O
O O
O HO
Streptobiosamine OH NH2 NHCH 3
HO OH
H3C
CH3 OH
OHC Kanamycin, R = H
Gentamicin
Streptomycin Amikacin, R = COCH(OH)CH2CH2NH2
DIFFERENT SOURCES OF ANTIBIOTICS:-
1. Gentamicin Micromonospora purpurea

2. Neomycin Streptomyces fradiae
3. Streptomycin Streptomyces griseus
4. Tobramycin Streptomyces tenebrarius
5. Framycetin Streptomyces decaries
6. Kanamycin Streptomyces kanamyceticus
7. Amikacin It is 1-L-(-)-4-amino-2-hydroxybutyryl kanamycin
1 PHARMAROCKS: THE WAY OF SUCCESS MR. AMAR M. RAVAL (9016312020)

MECHANISMS OF ACTION
Aminoglycosides have several potential antibiotic mechanisms, some as protein synthesis

inhibitors, although their exact mechanism of action is not fully known:
 They interfere with the proofreading process, causing increased rate of error in
synthesis with premature termination.
 Also, there is evidence of inhibition of ribosomal translocation where the peptidyl-tRNA
moves from the A-site to the P-site.
 They can also disrupt the integrity of bacterial cell membrane.
They bind to the bacterial 30S ribosomal subunit (some work by binding to the 50S subunit
There is a significant variability in the relationship between the dose administered and the
resultant plasma level in blood. Therapeutic drug monitoring (TDM) is necessary to obtain the
correct dose. These agents exhibit a post-antibiotic effect in which there is no or very little drug
level detectable in blood, but there still seems to be inhibition of bacterial re-growth. This is
due to strong, irreversible binding to the ribosome, and remains intracellular long after plasma
levels drop. This allows a prolonged dosage interval. Depending on their concentration they act
as bacteriostatic or bactericidal agents.
The protein synthesis inhibition of aminoglycosides does not usually produce a bactericidal
effect, let alone a rapid one as is frequently observed on susceptible Gram-negative bacilli.
Aminoglycosides competitively displace cell biofilm-associated Mg2+ and Ca2+ that link the
polysaccharides of adjacent lipopolysaccharide molecules. "The result is shedding of cell
membrane blebs, with formation of transient holes in the cell wall and disruption of the normal
permeability of the cell wall. This action alone may be sufficient to kill most susceptible Gram-
negative bacteria before the aminoglycoside has a chance to reach the 30S ribosome."
The antibacterial properties of aminoglycosides were believed to result from inhibition of
bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome. This
explanation, however, does not account for the potent bactericidal properties of these agents,
since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not
bactericidal. Recent experimental studies show that the initial site of action is the outer
bacterial membrane. The cationic antibiotic molecules create fissures in the outer cell
membrane, resulting in leakage of intracellular contents and enhanced antibiotic uptake. This
rapid action at the outer membrane probably accounts for most of the bactericidal activity.
Energy is needed for aminoglycoside uptake into the bacterial cell. Anaerobes have less energy
available for this uptake, so aminoglycosides are less active against anaerobes.
Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria,
such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria,
including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. The most
frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia,
complicated intraabdominal infections, complicated urinary tract infections, and nosocomial
respiratory tract infections. Usually, once cultures of the causal organism are grown and their
susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.
Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of
aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity
and inconvenient route of administration) except for multiple drug resistant strains.
Infections caused by gram-positive bacteria can also be treated with aminoglycosides, but other
types of antibiotics are more potent and less damaging to the host. In the past the
aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal
infections for their synergistic effects, particularly in endocarditis. One of the most frequent
combinations is ampicillin (a beta-lactam, or penicillin-related antibiotic) and gentamicin. Often,
hospital staff refer to this combination as "amp and gent" or more recently called "pen and
gent" for penicillin and gentamicin.
Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi, and viruses
Nonsense suppression
The interference with DNA proofreading has been exploited to treat genetic diseases which
result from premature stop codes (leading to early termination of protein synthesis and
truncated proteins). Aminoglycosides can cause the cell to overcome the stop code, insert a
random amino acid, and express a full-length protein.
The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory
to induce them to grow full-length proteins. CF is caused by a mutation in the gene coding for
the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In approximately 10%
of CF cases, the mutation in this gene causes its early termination during translation, leading to
the formation of is truncated and non-functional CFTR protein. It is believed that gentamicin
distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the
termination codon, causing the ribosome to "skip" over the stop sequence and to continue with
the normal elongation and production of the CFTR protein.
Routes of administration
Since they are not absorbed from the gut, they are administered intravenously and
intramuscularly. Some are used in topical preparations for wounds. Oral administration can be
used for gut decontamination (e.g., in hepatic encephalopathy). Tobramycin may be
administered in a nebulized form.
Clinical use
The recent emergence of infections due to Gram-negative bacterial strains with advanced
patterns of antimicrobial resistance has prompted physicians to reevaluate the use of these
antibacterial agents. This revived interest in the use of aminoglycosides has brought back to
light the debate on the two major issues related to these compounds, namely the spectrum of
antimicrobial susceptibility and toxicity. Current evidence shows that aminoglycosides do retain
activity against the majority of Gram-negative clinical bacterial isolates in many parts of the
world. Still, the relatively frequent occurrence of nephrotoxicity and ototoxicity during
aminoglycoside treatment makes physicians reluctant to use these compounds in everyday
practice. Recent advances in the understanding of the effect of various dosage schedules of
aminoglycosides on toxicity have provided a partial solution to this problem, although more
research still needs to be done in order to overcome this problem entirely.
Resistance Development
Aminoglycosides develops resistance very fastly. These are inactivated by N-acetyl transferase,
N-adenyl transferase and O-Phosphorylase. These enzymes inactivate the antibiotics so newer
antibiotics like kanamycin and gentamicin are 2-deoxy streptamine derivative and amikacin has
no free amino group on 1-position.

ANTI ARRHYTHMIC DRUGS
Heart is the major organ that supplies oxygen to the whole body. Heart contains two atria
(right and left) and two ventricles. There is coronary artery that supplies 11% of total oxygen
to the heart and other nutrients. Heart is composed of cardiac muscle that has intrinsic activity
and spontaneous impulse are generated by pace maker (Sinoartrial node) that sweeps over
atria AV nodes and his purkinje fibres; so there is contraction and relaxation of cardiac muscle.
Total 0.8 tme is required, 0.1 for contraction of artrias and 0.3 second for contraction of
ventricles and then complete relaxation of 0.4 second. Both atrias and ventricles beat at the
same time.
Physiology of heart muscle
Normal heart muscle electrical activity curve Heart beats 72

times/minute
her
0.4 second 0.1 second
Diastole atrial
systole
(relaxation) 0.3
second
Ventricle

At the resting stage the potential inside the muscle is negative. At 0 phase there is influx of Na +
ions that causes rapid depolarization of cell and muscle contract as potential reaches to
maximum and generate action potential. After that in 1 phase, there is partial repolarization.
Further in 2 phase (Plateau phase) there is release of caCa2+ ions from sarcoplasmic reticulum
that causes slow inward current. In 3 phase there is repolarization causes influx of k+ ions and
then at last 4 phase comes.
Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal
rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular
tachycardia, and ventricular fibrillation.
Many attempts have been made to classify antiarrhythmic agents. The problem arises from the
fact that many of the antiarrhythmic agents have multiple modes of action, making any
classification imprecise.
Vaughan Williams classification
The Singh Vaughan Williams classification, introduced in 1970 based on the seminal work of
Bramah N. Singh in his doctoral thesis at Oxford where Vaughan Williams was his advisor and
on subsequent work by Singh and his colleagues in the United States, is one of the most widely
used classification schemes for antiarrhythmic agents. This scheme classifies a drug based on
the primary mechanism of its antiarrhythmic effect. However, its dependence on primary
mechanism is one of the limitations of the Singh-VW classification, since many antiarrhythmic
agents have multiple action mechanisms. Amiodarone, for example, has effects consistent with
all of the first four classes. Another limitation is the lack of consideration within the Singh-VW
classification system for the effects of drug metabolites. Procainamide—a class Ia agent whose
metabolite N- acetyl procainamide (NAPA) has a class III action—is one such example. A
historical limitation was that drugs such as digoxin and adenosine – important antiarrhythmic
agents – had no place at all in the VW classification system. This has since been rectified by the
inclusion of class V
There are five main classes in the Singh Vaughan Williams classification of antiarrhythmic
agents:
 Class I agents interfere with the sodium (Na+) channel.

 Class II agents are anti-sympathetic nervous system agents. Most agents in this class are
beta blockers.
 Class III agents affect potassium (K+) efflux.
 Class IV agents affect calcium channels and the AV node.
 Class V agents work by other or unknown mechanisms.

Overview table
Known
Class Examples Mechanism Clinical uses [1]
as
 Ventricular
arrhythmias
 prevention of
paroxysmal recurrent
 Quinidine
fast- (Na+) channel block atrial fibrillation
 Procainamide
Ia channel (intermediate (triggered by vagal
 Disopyramide
blockers association/dissociation) overactivity),
*procainamide in
Wolff-Parkinson-White
syndrome
 treatment and
prevention during and
immediately after
myocardial infarction,
 Lidocaine though this practice is
 Phenytoin (Na+) channel block (fast now discouraged given
Ib
 Mexiletine association/dissociation) the increased risk of
asystole
o ventricular
tachycardia
o atrial fibrillation
 prevents paroxysmal
atrial fibrillation
 treats recurrent
 Flecainide tachyarrhythmias of
 Propafenone (Na+) channel block (slow abnormal conduction
Ic
 Moricizine association/dissociation) system.
 contraindicated
immediately post-
myocardial infarction.
 Propranolol
beta blocking  decrease myocardial
Beta-  Esmolol
II Propranolol also shows infarction mortality
blockers  Timolol
some class I action  prevent recurrence of
 Metoprolol

 Atenolol tachyarrhythmias
 Bisoprolol
 In Wolff-Parkinson-
 Amiodarone White syndrome
 Sotalol K+ channel blocker  (sotalol:) ventricular
 Ibutilide tachycardias and atrial
III
 Dofetilide Sotalol is also a beta fibrillation
 E-4031 blocker  (Ibutilide:) atrial flutter
and atrial fibrillation
 prevent recurrence of
paroxysmal
supraventricular
slow-  Verapamil
tachycardia
IV channel  Diltiazem Ca2+ channel blocker
 reduce ventricular rate
blockers
in patients with atrial
fibrillation
Used in supraventricular
 Adenosine Work by other or arrhythmias, especially in
V  Digoxin unknown mechanisms Heart Failure with Atrial
(Direct nodal inhibition). Fibrillation, contraindicated in
ventricular arrhythmias.
Class I agents
The class I antiarrhythmic agents interfere with the sodium channel. Class I agents are grouped
by what effect they have on the Na+ channel, and what effect they have on cardiac action
potentials.
Class 1 agents are called Membrane Stabilizing agents. The 'stabilizing' is the word used to
describe the decrease of excitogenicity of the plasma membrane which is brought about by
these agents. (Also noteworthy is that a few class 2 agents like propranolol also have a
membrane stabilizing effect.)
Class I agents are divided into three groups (1a, 1b and 1c) based upon their effect on the
length of the action potential.
 1A lengthens the action potential (right shift)

 1B shortens the action potential (left shift)
 1C does not significantly affect the action potential (no shift)

Class Ia agent decreasing Vmax, thereby increasing action
Class Ib Class Ic
potential duration.
Class II agents
Class II agents are conventional beta blockers. They act by blocking the effects of
catecholamines at the β1-adrenergic receptors, thereby decreasing sympathetic activity on the
heart. These agents are particularly useful in the treatment of supraventricular tachycardias.
They decrease conduction through the AV node.
Class II agents include atenolol, esmolol, propranolol, and metoprolol.
Class III agents
Class III
Class III agents predominantly block the potassium channels, thereby prolonging
repolarization.[5] Since these agents do not affect the sodium channel, conduction velocity is
not decreased. The prolongation of the action potential duration and refractory period,
combined with the maintenance of normal conduction velocity, prevent re-entrant
arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become
refractory). Drugs include: amiodarone, ibutilide, sotalol, dofetilide, and dronedarone.
Class IV agents
Class IV agents are slow calcium channel blockers. They decrease conduction through the AV
node, and shorten phase two (the plateau) of the cardiac action potential. They thus reduce the
contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta
blockers, they allow the body to retain adrenergic control of heart rate and contractility.
Class IV agents include verapamil and diltiazem.

Other agents ("Class V")
Since the development of the original Vaughan-Williams classification system, additional agents
have been used that don't fit cleanly into categories I through IV.
Some sources use the term "Class V". However, they are more frequently identified by their
precise mechanism.
Agents include:
 Digoxin, which decreases conduction of electrical impulses through the AV node and
increases vagal activity via its central action on the central nervous system.
 Adenosine
 Magnesium sulfate, which has been used for torsades de pointes.
Sicilian Gambit classification
Another approach, known as the "Sicilian Gambit", placed a greater approach on the underlying
mechanism.
It presents the drugs on two axes, instead of one, and is presented in tabular form. On the Y
axis, each drug is listed, in approximately the Vaughan Williams order. On the X axis, the
channels, receptors, pumps, and clinical effects are listed for each drug, with the results listed
in a grid. It is therefore not a true classification in that it does not aggregate drugs into
categories.[14]
OCH 3
OCH 3
Verapamil CN
H3CO
N
H3CO CH3
H3C CH3

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also

referred to as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal
anti-inflammatory medicines (NSAIMs), are drugs with analgesic and antipyretic (fever-
reducing) effects and which have, in higher doses, anti-inflammatory effects.
The term "nonsteroidal" is used to distinguish these drugs from steroids, which, among a broad
range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As
analgesics, NSAIDs are unusual in that they are non-narcotic.
The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen, all of
which are available over the counter in many areas.

Mechanism of action
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both
the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. COX catalyzes the
formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the
cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as
messenger molecules in the process of inflammation. This mechanism of action was elucidated
by John Vane (1927–2004), who later received a Nobel Prize for his work (see Mechanism of
action of aspirin). Many aspects of the mechanism of action of NSAIDs remain unexplained, for
this reason further COX pathways are hypothesized. The COX-3 pathway was believed to fill
some of this gap but recent findings make it appear unlikely that it plays any significant role in
humans and alternative explanation models are proposed.
NSAIDS have antipyretic activity and can be used to treat fever. Fever is caused by elevated
levels of prostaglandin E2, which alters the firing rate of neurons within the hypothalamus that
control thermoregulation. Antipyretics work by inhibiting the enzyme COX, which causes the
general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus. PGE2 signals to
the hypothalamus to increase the body's thermal set point. Ibuprofen has been shown to be
more effective as an antipyretic than acetaminophen. Arachidonic acid is the precursor
substrate for cyclooxygenase leading to the production of prostaglandins F,D & E.
Classification
NSAIDs can be classified based on their chemical structure or mechanism of action. Older
NSAIDs were known long before their mechanism of action was elucidated and were for this
reason classified by chemical structure or origin. Newer substances are more often classified by
mechanism of action.
O F
Salicylates:- HOOC
OCOCH 3 O COOH
F
COOH HO OH
Aspirin Salsalate Diflunisal

Propionic Acid Derivatives:- Naproxen Ketoprofen
CH3
CH3 O CH3
H3C
CH COOH COOH
COOH
H3C
Ibuprofen H3CO
2-(6-methoxynaphthalen-2-yl)propanoic acid
2-[p-(isobutyl)phenyl]propanoic acid 2-(3-benzoylphenyl)propanoic acid
CH3
Fenoprofen Flurbiprofen CH Oxprozin
3
O O
COOH CH COOH
CH 2CH 2COOH
F N
2-(2-fluorobiphenyl-4-yl)propanoic acid
2-(3-phenoxyphenyl)propanoic acid
Acetic Acid Derivatives:-

4 Nabumetone(Prodrug) Diclofenac Sod.
H3CO 5 3
CH 2CH 2COCH 3
- +
CH 2COOH CH 2COO Na
2
Cl
6 CH3
N H3CO
7 1 NH
4-(6-methoxynaphthalen-2-yl)butan-2-one
Indomethacin Cl
Etodolac {2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
5 4 3 4
6 F 5 3
CH 2COOH
Cl
O 2
[1-(4-chlorophenyl)-6-methoxy-
7 1 2 6 CH3
2-methyl-1H-indol-3-yl]acetic acid
CH 2COOH 1
8 N H5C2 7
Ketorolac H5C2 H
Sulindac
(1,8-diethyl-1,3,4,9-tetrahydropyrano
[3,4-b]indol-1-yl)acetic acid (Prodrug)
N COOH Tolmatin
O H3C
H3C S
5-benzoyl-2,3-dihydro-
1H-pyrrolizine-1-carboxylic acid N COOH O
O {(1Z)-5-fluoro-2-methyl-1-[4-(methylsulfinyl)
CH3 -benzylidene]-1H-inden-3-yl}acetic acid
[Enolic acid (Oxicam) derivatives

Piroxicam, Meloxicam, Tenoxicam, Droxicam, Lornoxicam, Isoxicam
Oxicam Derivatives:-
Piroxicam Meloxicam O N Tenoxicam
OH
HO O CH3
5 4 NH S OH O
6
3 NH
N N CH NH N
N CH S 3
7
S 2 3
O O N
8 1 S S CH3
O O 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)
-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide O O
4-hydroxy-2-methyl-N-(pyridin-2-yl)- 4-hydroxy-2-methyl-N-(pyridin-2-yl)-2H-thieno
2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide [3,2-e][1,2]thiazine-3-carboxamide 1,1-dioxide

Anthranilic Acid (Fenamic) Derivatives:-
Mefenamic Acid Meclofenamic acid Flufenamic acid
COOH COOH COOH
NH CH3 NH Cl NH
CH3 Cl CH3 CF 3
2-[(2,3-dimethylphenyl) 2-[(2,6-dichloro-3-methylphenyl) 2-{[3-(trifluoromethyl)phenyl]

amino]benzoic acid amino]benzoic acid amino}benzoic acid
Tolfenamic acid
Selective COX-2 inhibitors (Coxibs)
 Celecoxib (FDA alert)
 Rofecoxib (withdrawn from market)
 Valdecoxib (withdrawn from market)
 Parecoxib FDA withdrawn
 Lumiracoxib TGA cancelled registration
 Etoricoxib FDA withdrawn
 Firocoxib used in dogs and horses
Sulphonanilides
 Nimesulide (systemic preparations are banned by several countries for the potential risk
of hepatotoxicity)
Others
 Acetaminophen acts by inhibiting COX-2 and to a lesser degree COX-1
 Licofelone acts by inhibiting LOX (lipooxygenase) & COX and hence known as 5-LOX/COX
inhibitor
Main practical differences
NSAIDs within a group will tend to have similar characteristics and tolerability. There is little
difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather,
differences among compounds tend to be with regards to dosing regimens (related to the
compound's elimination half-life), route of administration, and tolerability profile.
Regarding adverse effects, selective COX-2 inhibitors have lower risk of gastrointestinal
bleeding, but a substantially more increased risk of myocardial infarction than the increased
risk from nonselective inhibitors.[13] Some data also supports that the partially selective
nabumetone is less likely to cause gastrointestinal events. The nonselective naproxen appears
to be risk-neutral with regard to cardiovascular events.
A consumer report noted ibuprofen, naproxen and salsalate to be less expensive than other
NSAIDs and to be essentially as effective and safe as any of them when used appropriately in
treating osteoarthritis and pain.

Uses
NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and
inflammation are present. Research continues into their potential for prevention of colorectal
cancer, and treatment of other conditions, such as cancer and cardiovascular disease.
NSAIDs are generally indicated for the symptomatic relief of the following conditions:
 Rheumatoid arthritis
 Osteoarthritis
 Inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's
syndrome)
 Acute gout
 Dysmenorrhoea (menstrual pain)
 Metastatic bone pain
 Headache and migraine
 Postoperative pain
 Mild-to-moderate pain due to inflammation and tissue injury
 Pyrexia (fever)
 Ileus
 Renal colic
 They are also given to neonate infants whose ductus arteriosus is not closed within 24
hours of birth
Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of
platelet aggregation. This is useful in the management of arterial thrombosis and prevention of
adverse cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of
thromboxane -A.
In 2001 NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses
sold annually in the United States.
Pharmacokinetics
Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3-5. They are
absorbed well from the stomach and intestinal mucosa. They are highly protein-bound in
plasma (typically >95%), usually to albumin, so that their volume of distribution typically
approximates to plasma volume. Most NSAIDs are metabolised in the liver by oxidation and
conjugation to inactive metabolites which are typically excreted in the urine, although some
drugs are partially excreted in bile. Metabolism may be abnormal in certain disease states, and
accumulation may occur even with normal dosage.
Ibuprofen and diclofenac have short half-lives (2–3 hours). Some NSAIDs (typically oxicams)
have very long half-lives (e.g. 20–60 hours).
Adverse effects
The widespread use of NSAIDs has meant that the adverse effects of these drugs have become
increasingly prevalent. The two main adverse drug reactions (ADRs) associated with NSAIDs
relate to gastrointestinal (GI) effects and renal effects of the agents.
These effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer
perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy. An
estimated 10-20% of NSAID patients experience dyspepsia, and NSAID-associated upper
gastrointestinal adverse events are estimated to result in 103,000 hospitalizations and 16,500
deaths per year in the United States, and represent 43% of drug-related emergency visits. Many
of these events are avoidable; a review of physician visits and prescriptions estimated that
unnecessary prescriptions for NSAIDs were written in 42% of visits.
NSAIDs, like all drugs, may interact with other medications. For example, concurrent use of
NSAIDs and quinolones may increase the risk of quinolones' adverse central nervous system
effects, including seizure.
Stimilus
Disturbance of cell membranes
Phospholipids
Phospholipase inhibitors
Corticosteroids Phospholipase
Arachidonic
acid
Cyclooxygenase Lipoxygenase
NSAIDS, ASA Lipoxygenase inhibitors
Leukotrines
Prostaglandin Prostacyclines
Thromboxane Receptor level antagonists
LTC4/LTD4 LTB4
Leukocyte modulation Phagocyte

Alteration of vascular Attraction,
permeability, bronchial activation
constriction, increased
secrtion Colchicine
Inflammation
Bronchospam, Inflammation
Congestion,
Mucos plugging

Scheme for mediators from arachidonic acid and site of drug action
Combinational risk
If a COX-2 inhibitor is taken, one should not use a traditional NSAID (prescription or over-the-
counter) concomitantly.[20] In addition, patients on daily aspirin therapy (e.g. for reducing
cardiovascular risk) need to be careful if they also use other NSAIDs, as the latter may block[the
cardioprotective effects of aspirin.
Cardiovascular
A recent meta-analysis of all trials comparing NSAIDs found an 80% increase in the risk of
myocardial infarction with both newer COX-2 antagonists and high dose traditional anti-
inflammatories compared with placebo.
NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of symptomatic heart
failure in patients without a history of cardiac disease. In patients with such a history, however,
use of NSAIDs (aside from low-dose aspirin) was associated with more than 10-fold increase in
heart failure.[22] If this link is found to be causal, NSAIDs are estimated to be responsible for up
to 20 percent of hospital admissions for congestive heart failure.
In patients with already established heart failure, NSAIDs increase mortaility with a hazard ratio
of approximately 1.2-1.3 for naproxen and ibuprofen, 1.7 for rofecoxib and celecoxib, and 2.1
for diclofenac.
Gastrointestinal
The main adverse drug reactions (ADRs) associated with use of NSAIDs relate to direct and
indirect irritation of the gastrointestinal (GI) tract. NSAIDs cause a dual insult on the GI tract:
the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2
reduces the levels of protective prostaglandins. Inhibition of prostaglandin synthesis in the GI
tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished
mucus secretion and diminished trophic effects on epithelial mucosa.
Common gastrointestinal ADRs include:
 Nausea/Vomiting
 Dyspepsia
 Gastric ulceration/bleeding.
 Diarrhea
Risk of ulceration increases with duration of therapy, and with higher doses. In attempting to
minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time,
a practice which studies show is not often followed. Recent studies show that over 50% of
patients taking NSAIDs have sustained damage to their small intestine. Studies show that risk of
ulceration is less with nabumetone than with ibuprofen alone.
There are also some differences in the propensity of individual agents to cause gastrointestinal
ADRs. Indomethacin, ketoprofen and piroxicam appear to have the highest prevalence of
gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.
Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations which are
claimed to reduce the incidence of gastrointestinal ADRs. Similarly, there is a belief that rectal
formulations may reduce gastrointestinal ADRs. However, in consideration of the mechanism of

such ADRs and indeed in clinical practice, these formulations have not been shown to have a
reduced risk of GI ulceration.
Commonly, gastric (but not necessarily intestinal) adverse effects can be reduced through
suppressing acid production, by concomitant use of a proton pump inhibitor, e.g. omeprazole,
esomeprazole; or the prostaglandin analogue misoprostol. Misoprostol is itself associated with
a high incidence of gastrointestinal ADRs (diarrhea). While these techniques may be effective,
they prove to be expensive for maintenance therapy.
Inflammatory bowel disease
NSAIDs are never to be used in individuals with inflammatory bowel disease (e.g., Crohn's
disease or ulcerative colitis) due to their tendency to cause gastric bleeding and form ulceration
in the gastric lining. Pain relievers such as paracetamol (also known as acetaminophen) or drugs
containing codeine (which slows down bowel activity) are safer medications for pain relief in
IBD.
Renal
NSAIDs are also associated with a relatively high incidence of renal adverse drug reactions
(ADRs). The mechanism of these renal ADRs is due to changes in renal haemodynamics (blood
flow), ordinarily mediated by prostaglandins, which are affected by NSAIDs. Prostaglandins
normally cause vasodilation of the afferent arterioles of the glomeruli. This helps maintain
normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of renal function.
This is particularly important in renal failure where the kidney is trying to maintain renal
perfusion pressure by elevated angiotensin II levels. At these elevated levels, angiotensin II also
constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole one it
normally constricts. Prostaglandins serve to dilate the afferent arteriole; by blocking this
prostaglandin-mediated effect, particularly in renal failure, NSAIDs cause unopposed
constriction of the afferent arteriole and decreased renal perfusion pressure. Horses are
particularly prone to these adverse affects compared with other domestic animal species.
Common ADRs associated with altered renal function include:
 Salt and fluid retention
 Hypertension (high blood pressure)
These agents may also cause renal impairment, especially in combination with other
nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an
ACE inhibitor and a diuretic - the so-called "triple whammy" effect.
In rarer instances NSAIDs may also cause more severe renal conditions:
 Interstitial nephritis
 Nephrotic syndrome
 Acute renal failure
 Acute tubular necrosis
NSAIDs in combination with excessive use of phenacetin and/or paracetamol may lead to
analgesic nephropathy.
Photosensitivity
Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs. It is
somewhat ironic that these anti-inflammatory agents may themselves produce inflammation in
combination with exposure to sunlight. The 2-arylpropionic acids have proven to be the most

likely to produce photosensitivity reactions, but other NSAIDs have also been implicated
including piroxicam, diclofenac and benzydamine.
Benoxaprofen, since withdrawn due to its hepatotoxicity, was the most photoactive NSAID
observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-
arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety. The specific
absorbance characteristics of the different chromophoric 2-aryl substituents, affects the
decarboxylation mechanism. While ibuprofen is somewhat of an exception, having weak
absorption, it has been reported to be a weak photosensitising agent.
During pregnancy
NSAIDs are not recommended during pregnancy, particularly during the third trimester. While
NSAIDs as a class are not direct teratogens, they may cause premature closure of the fetal
ductus arteriosus and renal ADRs in the fetus. Additionally, they are linked with premature
birth. Aspirin, however, is used together with heparin in pregnant women with
antiphospholipid antibodies.
In contrast, paracetamol (acetaminophen) is regarded as being safe and well-tolerated during
pregnancy. Doses should be taken as prescribed, due to risk of hepatotoxicity with overdoses.
In France, the country's health agency contraindicates the use of NSAIDs, including aspirin, after
the sixth month of pregnancy.
Other
Common adverse drug reactions (ADR), other than listed above, include: raised liver enzymes,
headache, dizziness. Uncommon ADRs include: hyperkalaemia, confusion, bronchospasm, rash.
Rapid and severe swelling of the face and/or body. Ibuprofen may also rarely cause irritable
bowel syndrome symptoms.
Most NSAIDs penetrate poorly into the central nervous system (CNS). However, the COX
enzymes are expressed constitutively in some areas of the CNS, meaning that even limited
penetration may cause adverse effects such as somnolence and dizziness.
In very rare cases, ibuprofen can cause aseptic meningitis.
As with other drugs, allergies to NSAIDs might exist. While many allergies are specific to one
NSAID, up to 1 in 5 people may have unpredictable cross-reactive allergic responses to other
NSAIDs as well.
Drug Interactions
NSAIDs reduce renal blood flow and thereby decrease the efficacy of diuretics, and inhibit the
elimination of lithium and methotrexate.
NSAIDs cause hypocoagulability, which may be serious when combined with other drugs that
also decrease blood clotting, such as warfarin.
NSAIDS may aggravate hypertension (high blood pressure) and thereby antagonize the effect of
antihypertensives, such as ACE Inhibitors.
Chirality
Most NSAIDs are chiral molecules (diclofenac is a notable exception). However, the majority are
prepared in a racemic mixture. Typically, only a single enantiomer is pharmacologically active.
For some drugs (typically profens), an isomerase enzyme exists in vivo which converts the
inactive enantiomer into the active form, although its activity varies widely in individuals. This
phenomenon is likely to be responsible for the poor correlation between NSAID efficacy and

plasma concentration observed in older studies, when specific analysis of the active enantiomer
was not performed.
Ibuprofen and ketoprofen are now available in single, active enantiomer preparations
(dexibuprofen and dexketoprofen), which purport to offer quicker onset and an improved side-
effect profile. Naproxen has always been marketed as the single active enantiomer.
Selective COX inhibitors
The discovery of COX-2 in 1991 by Daniel L. Simmons at Brigham Young University raised the
hope of developing an effective NSAID without the gastric problems characteristic of these
agents. It was thought that selective inhibition of COX-2 would result in anti-inflammatory
action without disrupting gastroprotective prostaglandins.
Selective COX-2 Inhibitors:-
Celecoxib Rofecoxib Valdecoxib
H3CO 2S
H2NO 2S H2NO 2S CH3
N CF 3 O
N
O
O N
4-[5-phenyl-3-(trifluoromethyl)- 4-[4-(methylsulfonyl)phenyl]- 4-(5-methyl-3-phenyl-4,5-dihydro-

1H-pyrazol-1-yl]benzenesulfonamide 3-phenylfuran-2(5H)-one 1,2-oxazol-4-yl)benzenesulfonamide
COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many
normal physiological processes. One of these is in the stomach lining, where prostaglandins
serve a protective role, preventing the stomach mucosa from being eroded by its own acid.
When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower
stomach prostaglandin levels, these protective effects are lost and ulcers of the stomach or
duodenum and potentially internal bleeding can result. COX-2 is an enzyme facultatively
expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of
NSAIDs.
The relatively selective COX-2 inhibiting oxicam, meloxicam, was the first step towards
developing a true COX-2 selective inhibitor. Coxibs, the newest class of NSAIDs, can be
considered as true COX-2 selective inhibitors, and include celecoxib, rofecoxib, valdecoxib,
parecoxib and etoricoxib.
Acetaminophen does also work mainly by blocking COX-2, unlike the newly developed COX-2
inhibitors it has weaker peripheral inhibitory activity.
Controversies with COX-2 inhibitors
While it was hoped that this COX-2 selectivity would reduce gastrointestinal adverse drug
reactions (ADRs), there is little conclusive evidence that this is true. The original study touted by
Searle (now part of Pfizer), showing a reduced rate of ADRs for celecoxib, was later revealed to
be based on preliminary data - the final data showed no significant difference in ADRs when
compared with diclofenac.
Rofecoxib however, which has since been withdrawn, had been shown to produce significantly
fewer gastrointestinal ADRs compared with naproxen. This study, the VIGOR trial, raised the
issue of the cardiovascular safety of the coxibs - a statistically insignificant increase in the
incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from
the APPROVe trial, showed a relative risk of cardiovascular events of 1.97 versus placebo - a
result which resulted in the worldwide withdrawal of rofecoxib in October 2004.
COX-3 inhibitors
Simmons also co-discovered COX-3 in 2002 and analyzed this new isozyme's relation to
paracetamol (acetaminophen), arguably the most widely used analgesic drug in the world. The
authors postulated that inhibition of COX-3 could represent a primary central mechanism by
which these drugs decrease pain and possibly fever.
The relevance of this research has been called into question as the putative COX-3 gene
encodes proteins with completely different amino acid sequences than COX-1 or COX-2.
Disease-modifying antirheumatic drugs
Methotrexate Hydroxychloroquine
Auranofin, a gold salt

Disease-modifying antirheumatic drugs (DMARDs) is a category of otherwise unrelated drugs
defined by their use in rheumatoid arthritis to slow down disease progression. The term is often
used in contrast to non-steroidal anti-inflammatory drug, which refers to agents that treat the
inflammation but not the underlying cause.
The term "antirheumatic" can be used in similar contexts, but without making a claim about
an effect on the course.
Terminology
Although their use was first propagated in rheumatoid arthritis (hence their name) the term has
come to pertain to many other diseases, such as Crohn's disease, lupus erythematosus (SLE),
idiopathic thrombocytopenic purpura (ITP), myasthenia gravis and various others. Many of
these are autoimmune disorders, but others, such as ulcerative colitis, are probably not (there
is no consensus on this).
The term was originally introduced to indicate a drug that reduced evidence of processes
thought to underlie the disease, such as a raised erythrocyte sedimentation rate, reduced
haemoglobin level, raised rheumatoid factor level and more recently, raised C-reactive protein
level. More recently, the term has been used to indicate a drug that reduces the rate of damage
to bone and cartilage. DMARDs can be further subdivided into traditional small molecular mass
drugs synthesised chemically and newer 'biological' agents produced through genetic
engineering.
Some DMARDs (eg the Purine synthesis inhibitors) are mild chemotherapeutics but use a side-
effect of chemotherapy - immunosuppression - as its main therapeutical benefit.
Members
Drug Mechanism
adalimumab TNF inhibitor
azathioprine Purine synthesis inhibitor
chloroquine and Suppression of IL-1 & TNF-alpha, induce apoptosis of
hydroxychloroquine (antimalarials) inflammatory cells and increase chemotactic factors
ciclosporin (Cyclosporin A) calcineurin inhibitor
D-penicillamine Reducing numbers of T-lymphocytes etc.
etanercept TNF inhibitor
golimumab TNF inhibitor
gold salts (sodium aurothiomalate, unknown - proposed mechanism: inhibits macrophage
auranofin) activation
infliximab TNF inhibitor
leflunomide Pyrimidine synthesis inhibitor

methotrexate (MTX) Antifolate
minocycline 5-LO inhibitor
chimeric monoclonal antibody against CD20 on B-cell
rituximab
surface
Suppression of IL-1 & TNF-alpha, induce apoptosis of
sulfasalazine (SSZ)
inflammatory cells and increase chemotactic factors
Although these agents operate by different mechanisms, many of them can have similar impact
upon the course of a condition.
Some of the drugs can be used in combination.
Alternatives
When treatment with DMARDs fails, cyclophosphamide or steroid pulse therapy is often used
to stabilise uncontrolled autoimmune disease. Some severe autoimmune diseases are being
treated with bone marrow transplants in clinical trials, usually after cyclophosphamide therapy
has failed.
Combinations of DMARDs are often used together, because each drug in the combination can
be used in smaller dosages than if it were given alone, thus reducing the risk of side effects.
Many patients receive an NSAID and at least one DMARD, sometimes with low-dose oral
glucocorticoids. If disease remission is observed, regular NSAIDs or glucocorticoid treatment
may no longer be needed. DMARDs help control arthritis but do not cure the disease. For that
reason, if remission or optimal control is achieved with a DMARD, it is often continued at a
maintenance dosage. Discontinuing a DMARD may reactivate disease or cause a “rebound
flare”, with no assurance that disease control will be reestablished upon resumption of the
medication, according to Arthritis & Rheumatism.
These agents are used to treat gout
Antigout agents
Gout also known as podagra when it involves thebig toe is a medical condition usually  FS
characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen eu
joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected bl
(~50% of cases). However, it may also present as tophi, kidney stones, or urate nephropathy. It uf
is caused by elevated levels of uric acid in the blood which crystallize and are deposited in xi
joints, tendons, and surrounding tissues. on
Diagnosis is confirmed clinically by the visualization of the characteristic crystals in joint fluid. sp
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine ty
improves symptoms. Once the acute attack has subsided, levels of uric acid are usually ar
lowered via lifestyle changes, and in those with frequent attacks allopurinol or probenicid ta

provide long-term prevention. z
Gout has increased in frequency in recent decades affecting approximately 1–2% of the o
Western population at some point in their lives. The increase is believed to be due to P n
increasing risk factors in the population, such as metabolic syndrome, longer life expectancy e
and changes in diet. Gout was historically known as "the disease of kings" or "rich man's  P
disease". e
U g
l
 oU
tl
Signs and symptoms
io
cr
ai
Gout presenting in the metatarsal-phalangeal joint of the big toe. Note the slight redness of sc
the skin overlying the joint. e
 P
Gout can present in a number of ways, although the most usual is a recurrent attack of acute
inflammatory arthritis (a red, tender, hot, swollen joint). The metatarsal-phalangeal joint at r
the base of the big toe is affected most often, accounting for half of cases. Other joints, such o
as the heels, knees, wrists and fingers, may also be affected. Joint pain usually begins over 2– b
4 hours and during the night. The reason for onset at night is due to the lower body e
temperature then. Other symptoms that may occur along with the joint pain include fatigue n
and a high fever. e
Long-standing elevated uric acid levels (hyperuricemia) may result in other symptomatology, c
including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead i
to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals d
precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.
 P
r
Cause
o
Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons, b
including diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. Renal e
underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of cases, while n
overproduction is the cause in less than 10%.] About 10% of people with hyperuricemia e
develop gout at some point in their lifetimes.[7] The risk, however, varies depending on the c
degree of hyperuricemia. When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dL), the i
risk is 0.5% per year, while in those with a level greater than 535 μmol/L (9 mg/dL), the risk is d
4.5% per year.
a
Lifestyle n
d
Dietary causes account for about 12% of gout, and include a strong association with the
consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other triggers include c

physical trauma and surgery. Recent studies have found dietary factors once believed to be o
associated are in fact not, including the intake of purine-rich vegetables and total protein. l
Coffee, vitamin C and dairy products consumption and physical fitness appear to decrease the c
risk. This is believed to be partly due to their effect in reducing insulin resistance. h
i
Genetics c
i
The occurrence of gout is partly genetic, contributing to about 60% of variability in uric acid n
level. A few rare genetic disorders, including familial juvenile hyperuricemic nephropathy, e
medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity, and
hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan
syndrome, are complicated by gout.
Medical conditions
Gout frequently occurs in combination with other medical problems. Metabolic syndrome, a
combination of abdominal obesity, hypertension, insulin resistance and abnormal lipid levels
occurs in nearly 75% of cases. Other conditions which are commonly complicated by gout
include: polycythemia, lead poisoning, renal failure, hemolytic anemia, psoriasis, and solid
organ transplants. A body mass index greater than or equal to 35 increases a male's risk of
gout threefold. Chronic lead exposure and lead-contaminated alcohol are risk factors for gout
due to the harmful effect of lead on kidney function.. Lesch-Nyhan syndrome is often
associated with gouty arthritis.
Medication
Diuretics have been associated with attacks of gout. However, a low dose of
hydrochlorothiazide does not seem to increase the risk. Other medicines that have been
associated include niacin and aspirin (acetylsalicylic acid). Cyclosporine is also associated with
gout, particularly when used in combination with hydrochlorothiazide, as are the
immunosuppressive drugs ciclosporin and tacrolimus.
Pathophysiology
O
O O
H
N N N
HN Xanthine Oxidase HN Xanthine Oxidase HN O
N N O N N
H N O N
H H H
Hypoxanthine Xanthine Uric Acid
Gout is a disorder of purine metabolism, and occurs when its final metabolite, uric acid,
crystallizes in the form of monosodium urate, precipitating in joints, on tendons, and in the
surrounding tissues. These crystals then trigger a local immune-mediated inflammatory
reaction with one of the key proteins in the inflammatory cascade being interleukin 1β. An
evolutionary loss of uricase, which breaks down uric acid, in humans and higher primates is
what has made this condition so common.
The triggers for precipitation of uric acid are not well understood. While it may crystallize at
normal levels, it is more likely to do so as levels increase. Other factors believed to be
important in triggering an acute episode of arthritis include cool temperatures, rapid changes
in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as
proteoglycans, collagens, and chondroitin sulfate. The increased precipitation at low
temperatures partly explains why the joints in the feet are most commonly affected. Rapid
changes in uric acid may occur due to a number of factors, including trauma, surgery,
chemotherapy, diuretics, and stopping or starting allopurinol.
Diagnosis
Gout on X-ray of a left foot. Typical location at the big toe joint. Note also the soft tissue
swelling at the lateral border of the foot.
Gout may be diagnosed and treated without further investigations in someone with
hyperuricemia and the classic podagra. Synovial fluid analysis should be done, however, if the
diagnosis is in doubt. X-rays, while useful for identifying chronic gout, have little utility in acute
attacks.
Synovial fluid
Spiked rods of uric acid (MSU) crystals from a synovial fluid sample photographed under a
microscope with polarized light. Formation of uric acid crystals in the joints is associated with
gout.
A definitive diagnosis of gout is based upon the identification of monosodium urate (MSU)
crystals in synovial fluid or a tophus. All synovial fluid samples obtained from undiagnosed
inflamed joints should be examined for these crystals. Under polarized light microscopy, they
have a needle-like morphology and strong negative birefringence. This test is difficult to
perform, and often requires a trained observer. The fluid must also be examined relatively
quickly after aspiration, as temperature and pH affect their solubility.
Blood tests
Hyperuricemia is a classic feature of gout; gout occurs, however, nearly half of the time
without hyperuricemia, and most people with raised uric acid levels never develop gout. Thus,
the diagnostic utility of measuring uric acid level is limited. Hyperuricemia is defined as a

plasma urate level greater than 420 μmol/L (7.0 mg/dL) in males and 360 μmol/L (6.0 mg/dL)
in females. Other blood tests commonly performed are white blood cell count, electrolytes,
renal function, and erythrocyte sedimentation rate (ESR). However, both the white blood cells
and ESR may be elevated due to gout in the absence of infection. A white blood cell count as
high as 4.0×109/L (40,000/mm3) has been documented.
Differential diagnosis
The most important differential diagnosis in gout is septic arthritis. This should be considered
in those with signs of infection or those who do not improve with treatment. To help with
diagnosis, a synovial fluid Gram stain and culture may be performed. Other conditions which
present similarly include pseudogout and rheumatoid arthritis. Gouty tophi, in particular when
not located in a joint, can be mistaken for basal cell carcinoma, or other neoplasms.
Prevention
Both lifestyle changes and medications can decrease uric acid levels. Dietary and lifestyle
choices that are effective include reducing intake of food such as meat and seafood,
consuming adequate vitamin C, limiting alcohol and fructose consumption, and avoiding
obesity. A low-calorie diet in obese men decreased uric acid levels by 100 µmol/L (1.7 mg/dL).
Vitamin C intake of 1,500 mg per day decreases the risk of gout by 45% compared to 250 mg
per day.] Coffee, but not tea, consumption is associated with a lower risk of gout.[28] Gout may
be secondary to sleep apnea via the release of purines from oxygen-starved cells. Treatment
of apnea can lessen the occurrence of attacks.
Treatment
The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can
be prevented by different drugs used to reduce the serum uric acid levels. Ice applied for 20 to
30 minutes several times a day decreases pain. Options for acute treatment include
nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids, while options for
prevention include allopurinol, probenecid and febuxostat. Lowering uric acid levels can cure
the disease. Treatment of comorbidities is also important.

Anti Gout Drugs:-
O O
H3C
HN Xanthine Oxidase HN
N N N COOH
N N O N N H3C
H H H
Allopurinol Alloxanthine Probenicid
O
O
O
S H3CO
NH CH3
N H3CO
O N
H3CO
Sulfinpyrazone Colchicine
O
OCH3
NSAIDs
NSAIDs are the usual first-line treatment for gout, and no specific agent is significantly more or
less effective than any other. Improvement may be seen within 4 hours, and treatment is
recommended for 1–2 weeks. They are not recommended, however in those with certain
other health problems, such as gastrointestinal bleeding, renal failure, or heart failure. While
indomethacin has historically been the most commonly used NSAID, an alternative, such as
ibuprofen, may be preferred due to its better side effect profile in the absence of superior
effectiveness. For those at risk of gastric side effects from NSAIDs, an additional proton pump
inhibitor may be given.
Colchicine
Colchicine is an alternative for those unable to tolerate NSAIDs. Its side effects (primarily
gastrointestinal upset) limit its usage. Gastrointestinal upset, however, depends on the dose,
and the risk can be decreased by using smaller yet still effective doses. Colchicine may interact
with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.
Steroids
Glucocorticoids have been found to be as effective as NSAIDs and may be used if

contraindications exist for NSAIDs.] They also lead to improvement when injected into the
joint; the risk of a joint infection must be excluded, however, as they worsen this condition.

Pegloticase
Pegloticase (Krystexxa) was approved to treat gout in 2010. It will be an option for the 3% of
people who are not adequately treated with other medications due to their association with
severe allergic reactions. Pegloticase is administered as an intravenous infusion every two
weeks. As of March 2010, however, no double blind, placebo controlled trials have been
completed.
Prophylaxis
A number of medications are useful for preventing further episodes of gout, including
allopurinol, probenecid, and febuxostat. They are not usually commenced until one to two
weeks after an acute attack has resolved, due to theoretical concerns of worsening the attack,
and are often used in combination with either an NSAID or colchicine for the first 3–6 months.
They are not recommended until a person has suffered two attacks of gout, unless destructive
joint changes, tophi, or urate nephropathy exist, as it is not until this point that medications
have been found to be cost effective. Urate-lowering measures should be increased until
serum uric acid levels are below 300-360 µmol/L (5.0-6.0 mg/dL) and are continued
indefinitely. If these medications are being used chronically at the time of an attack, it is
recommended they be continued.
Allopurinol blocks uric acid production, and is the most commonly used hypourecemic agent.
Long term therapy is safe and well tolerated, and can be used in people with renal impairment
or urate stones, although hypersensitivity occurs in a small number of individuals. Probenecid
is effective for treating hyperuricemia, but has been found to be less effective than
allopurinol. Febuxostat, a nonpurine inhibitor of xanthine oxidase, is now available as an
alternative to allopurinol. It is approved in both Europe and the United States.
Prognosis
Without treatment, an acute attack of gout will usually resolve in 5 to 7 days. However, 60% of
people will have a second attack within one year.[1] Those with gout are at increased risk of
hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease
and thus at increased risk of death. This may be partly due to its association with insulin
resistance and obesity, but some of the increased risk appears to be independent.
Without treatment, episodes of acute gout may develop into chronic gout with destruction of
joint surfaces, joint deformity, and painless tophi. These tophi occur in 30% of those who are
untreated for five years, often in the helix of the ear, over the olecranon processes, or on the
Achilles tendons. With aggressive treatment, they may dissolve. Kidney stones also frequently
complicate gout, affecting between 10 and 40% of people, and occur due to low urine pH
promoting the precipitation of uric acid. Other forms of chronic renal dysfunction may occur.
Epidemiology
Gout affects around 1–2% of the Western population at some point in their lifetimes, and is

becoming more common. Rates of gout have approximately doubled between 1990 and 2010.
This rise is believed to be due to increasing life expectancy, changes in diet, and an increase in
diseases associated with gout, such as metabolic syndrome and high blood pressure. A
number of factors have been found to influence rates of gout, including age, race, and the
season of the year. In men over the age of 30 and women over the age of 50, prevalence is
2%.
In the United States, gout is twice as likely in African American males as it is in European
Americans. Rates are high among the peoples of the Pacific Islands and the Māori of New
Zealand, but rare in Australian aborigines, despite a higher mean concentration of serum uric
acid in the latter group. It has become common in China, Polynesia, and urban sub-Saharan
Africa. Some studies have found attacks of gout occur more frequently in the spring. This has
been attributed to seasonal changes in diet, alcohol consumption, physical activity, and
temperature.
History
The word gout was initially used by Randolphus of Bocking, around 1200 AD. It is derived from
the Latin word gutta, meaning "a drop" (of liquid).
Gout has, however, been known since antiquity. Historically, it has been referred to as "the
king of diseases and the disease of kings" or "rich man's disease". The first documentation of
the disease is from Egypt in 2,600 BC in a description of arthritis of the big toe. The Greek
physician Hippocrates around 400 BC commented on it in his Aphorisms, noting its absence in
eunuchs and premenopausal women. Aulus Cornelius Celsus (30 AD) described the linkage
with alcohol, later onset in women, and associated kidney problems:
Again thick urine, the sediment from which is white, indicates that pain and disease are to be
apprehended in the region of joints or viscera... Joint troubles in the hands and feet are very
frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack
eunuchs or boys before coition with a woman, or women except those in whom the menses
have become suppressed... some have obtained lifelong security by refraining from wine,
mead and venery.
While in 1683, Thomas Sydenham, an English physician, described its occurrence in the early
hours of the morning, and its predilection for older males:
Gouty patients are, generally, either old men, or men who have so worn themselves out in
youth as to have brought on a premature old age - of such dissolute habits none being more
common than the premature and excessive indulgence in venery, and the like exhausting
passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning
he is awakened by a severe pain in the great toe; more rarely in the heel, ankle or instep. The
pain is like that of a dislocation, and yet parts feel as if cold water were poured over them.
Then follows chills and shivers, and a little fever... The night is passed in torture, sleeplessness,
turning the part affected, and perpetual change of posture; the tossing about of body being as
incessant as the pain of the tortured joint, and being worse as the fit comes on.
The Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of

urate crystals in 1679. In 1848 English physician Alfred Baring Garrod realized that this excess
uric acid in the blood was the cause of gout.
Research
A number of new medications are under study for treating gout, including anakinra,
canakinumab, and rilonacept. A recombinant uricase enzyme (rasburicase) is available; its use,
however, is limited, as it triggers an autoimmune response. Less antigenic versions are in
development.
Opioid
An opioid is a chemical that works by binding to opioid receptors, which are found principally in
the central nervous system and the gastrointestinal tract. The receptors in these organ systems
mediate both the beneficial effects and the side effects of opioids.
The analgesic (painkiller) effects of opioids are due to decreased perception of pain, decreased
reaction to pain as well as increased pain tolerance. The side effects of opioids include sedation,
respiratory depression, and constipation. Opioids can cause cough suppression, which can be
both an indication for opioid administration or an unintended side effect. Physical dependence
can develop with ongoing administration of opioids, leading to a withdrawal syndrome with
abrupt discontinuation. Opioids can produce a feeling of euphoria, motivating some to
recreationally use opioids.
Although the term opiate is often used as a synonym for opioid, the term opiate is properly
limited to only the natural alkaloids found in the resin of the opium poppy (Papaver
somniferum).

Classification
There are a number of broad classes of opioids:
 Natural opiates: alkaloids contained in the resin of the opium poppy, primarily
morphine, codeine, and thebaine, but not papaverine and noscapine which have a
different mechanism of action; The following could be considered natural opiates: The
leaves from Mitragyna speciosa (also known as Kratom) contain a few naturally-
occurring opioids, active via Mu- and Delta receptors. Salvinorin A, found naturally in
the Salvia divinorum plant, is a kappa-opioid receptor agonist.
 Semi-synthetic opioids: created from the natural opiates, such as hydromorphone,
hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine (heroin),
nicomorphine, dipropanoylmorphine, benzylmorphine and ethylmorphine and
buprenorphine;

 Fully synthetic opioids: such as fentanyl, pethidine, methadone, tramadol and
dextropropoxyphene;
 Endogenous opioid peptides, produced naturally in the body, such as endorphins,
enkephalins, dynorphins, and endomorphins.
 There are also drugs such as tramadol and tapentadol that are chemically not of the
opioid class, but do have agonist actions at the μ-opioid receptor. Although their exact
mechanism of action is not fully understood, they both have a dual mode of action, the
second mode of action appearing to be on the noradrenergic and serotonergic systems.
This second mechanism of action was discovered during testing in where the drugs
showed signs of analgesia even when naloxone, an opioid antagonist, was administered.
Some minor opium alkaloids and various substances with opioid action are also found
elsewhere, including molecules present in Kratom, Corydalis, and Salvia divinorum plants and
some species of poppy aside from Papaver somniferum and there are strains which produce
copious amounts of thebaine, an important raw material for making many semi-synthetic and
synthetic opioids. Of all of the more than 120 poppy species, only two produce morphine.
Amongst analgesics are a small number of agents which act on the central nervous system but
not on the opioid receptor system and therefore have none of the other (narcotic) qualities of
opioids although they may produce euphoria by relieving pain—a euphoria that, because of the
way it is produced, does not form the basis of habituation, physical dependence, or addiction.
Foremost amongst these are nefopam, orphenadrine, and perhaps phenyltoloxamine and/or
some other antihistamines. Tricyclic antidepressants have painkilling effect as well, but they're
thought to do so by indirectly activating the endogenous opioid system. The remainder of
analgesics work peripherally (i.e., not on the brain or spinal cord). Research is starting to show
that morphine and related drugs may indeed have peripheral effects as well, such as morphine
gel working on burns. Paracetamol is predominantly a centrally acting analgesic (non-narcotic)
which mediates its effect by action on descending serotoninergic (5-hydroxy triptaminergic)
pathways, to increase 5-HT release (which inhibits release of pain mediators). It also decreases
cyclo-oxygenase activity. It has recently been discovered that most or all of the therapeutic
efficacy of paracetamol is due to a metabolite ( AM404, making paracetamol a prodrug) which
enhances the release of serotonin and also interacts as with the cannabinoid receptors by
inhibiting the uptake of anandamide.
It has been discovered in 1953, that the human body, as well as those of some other animals,
naturally produce minute amounts of morphine and codeine and possibly some of their simpler
derivatives like heroin and dihydromorphine, in addition to the well known endogenous opioid
peptides. Some bacteria are capable of producing some semi-synthetic opioids such as
hydromorphone and hydrocodone when living in a solution containing morphine or codeine
respectively.
Many of the alkaloids and other derivatives of the opium poppy are not opioids or narcotics;
the best example is the smooth-muscle relaxant papaverine. Noscapine is a marginal case as it
does have CNS effects but not necessarily similar to morphine, and it is probably in a category

all its own.
Dextromethorphan (the stereoisomer of levomethorphan, a semi-synthetic opioid agonist) and
its metabolite dextrorphan have no opioid analgesic effect at all despite their structural
similarity to other opioids; instead they are potent NMDA antagonists and sigma 1 and 2-
receptor agonists and are used in many over-the-counter cough suppressants.
Salvinorin A is a unique selective, powerful ĸ-opioid receptor agonist. It is not properly
considered an opioid nevertheless, because 1) chemically, it is not an alkaloid; and 2) it has no
typical opioid properties: absolutely no anxiolytic or cough-suppressant effects. It is instead a
powerful hallucinogen.
Pharmacology
Opioids bind to specific opioid receptors in the central nervous system and other tissues. There
are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta), although up to
seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta)
receptors. Conversely, σ (Sigma) receptors are no longer considered to be opioid receptors
because: their activation is not reversed by the opioid inverse-agonist naloxone, they do not
exhibit high-affinity binding for classical opioids, and they are stereoselective for dextro-
rotatory isomers while the other opioid receptors are stereo-selective for laevo-rotatory
isomers. In addition, there are three subtypes of μ-receptor: μ1 and μ2, and the newly
discovered μ3. Another receptor of clinical importance is the opioid-receptor-like receptor 1
(ORL1), which is involved in pain responses as well as having a major role in the development of
tolerance to μ-opioid agonists used as analgesics. These are all G-protein coupled receptors
acting on GABAergic neurotransmission.The pharmacodynamic response to an opioid depends
upon the receptor to which it binds, its affinity for that receptor, and whether the opioid is an
agonist or an antagonist. For example, the supraspinal analgesic properties of the opioid
agonist morphine are mediated by activation of the μ1 receptor; respiratory depression and
physical dependence by the μ2 receptor; and sedation and spinal analgesia by the κ receptor.
Each group of opioid receptors elicits a distinct set of neurological responses, with the receptor
subtypes (such as μ1 and μ2 for example) providing even more [measurably] specific responses.
Unique to each opioid is its distinct binding affinity to the various classes of opioid receptors
(e.g. the μ, κ, and δ opioid receptors are activated at different magnitudes according to the
specific receptor binding affinities of the opioid). For example, the opiate alkaloid morphine
exhibits high-affinity binding to the μ-opioid receptor, while ketazocine exhibits high affinity to
ĸ receptors. It is this combinatorial mechanism that allows for such a wide class of opioids and
molecular designs to exist, each with its own unique effect profile. Their individual molecular
structure is also responsible for their different duration of action, whereby metabolic
breakdown (such as N-dealkylation) is responsible for opioid metabolism.

Relative Protein Lipid
Drug Nonionized Fraction
Potency[3] Binding Solubility[4]
Morphine 1 ++ ++ +
Meperidine 0.1 + +++ ++
Hydromorphone 10
Alfentanil 10-25 ++++ ++++ +++
Fentanyl 75-125 + +++ ++++
Remifentanil 250 +++ +++ ++
Sufentanil 500-1000 ++ ++++ ++++
Etorphine 1000-3000
+ very low, ++ low, +++ high,
++++ very high
Uses
Prescription use
Opioids have long been used to treat acute pain (such as post-operative pain). They have also
been found to be invaluable in palliative care to alleviate the severe, chronic, disabling pain of
terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis.
Contrary to popular belief, high doses are not necessarily required to control the pain of
advanced or end-stage disease, so long as the effects of tolerance (which means a physical
reaction which makes the body immune to analgesic as well as mental effects of opiates,
narcotics, and others) allow patients to often require a median dose in such patients being only
15 mg oral morphine every four hours (90 mg/24 hours). This means that 50% of patients
manage on lower doses, and requirements can level off for many months at a time, depending
on severity of pain, which varies. This is despite the fact that opioids have some of the greatest
potential for tolerance of any category of drugs, which essentially means in many cases, opioids
are a successful long-term care strategy for those in chronic pain as well as acute pain.
In recent years there has been an increased use of opioids in the management of non-
malignant chronic pain. This practice has grown from over 30 years experience in palliative care
of long-term use of strong opioids which has shown that addiction is rare when the drug is
being used for pain relief. The basis for the occurrence of iatrogenic addiction to opioids in this
setting being several orders of magnitude lower than the general population is the result of a
combination of factors. Open and voluminous communication and meticulous documentation
amongst patient, caretakers, physicians, and pharmacists is one part of this; the aggressive and
consistent use of opioid rotation, adjuvant analgesics, potentiators, and drugs which deal with
other elements of the pain (NSAIDS) and opioid side effects both improve the prognosis for the
patient and appear to contribute to the rarity of addiction in these cases. Unfortunately, in

most countries the use of opioids is subject to complex legal regulations, which often impede
proper medical use for pain control and thus result in unnecessary suffering for patients.
United States
The sole clinical indications for opioids in the United States, according to Drug Facts and
Comparisons, 2005, are:
 Moderate to severe pain, i.e., to provide analgesia or, in surgery, to induce and maintain
anesthesia, as well as allaying patient apprehension right before the procedure.
Fentanyl, oxymorphone, hydromorphone, and morphine are most commonly used for
this purpose, in conjunction with other drugs such as scopolamine, short and
intermediate-acting barbiturates, and benzodiazepines, especially midazolam which has
a rapid onset of action and lasts shorter than diazepam(Valium) or similar drugs. The
combination of morphine (or sometimes hydromorphone) with alprazolam(Xanax) or
midazolam(Dormicum) or other similar benzodiazepines with or without scopolamine
(rarely replaced with or used alongside Compazine, Zofran or other anti-nauseants) is
colloquially called "Milk of Amnesia" amongst anesthesiologists, hospital pharmacists,
physicians, radiologists, patients and others. The enhancement of the effects of each
drug by the others is useful in troublesome procedures like endoscopies, complicated
and difficult deliveries (pethidine and its relatives and piritramide where it is used are
favoured by many practitioners with morphine and derivatives as the second line),
incision & drainage of severe abcesses, intraspinal injections, and minor and moderate-
impact surgical procedures in patients unable to have general anesthesia due to allergy
to some of the drugs involved or other concerns.
 Cough (codeine, dihydrocodeine, ethylmorphine (dionine), hydromorphone and
hydrocodone, with morphine or methadone as a last resort.)
 Diarrhea (generally loperamide, difenoxin or diphenoxylate; but paregoric, powdered
opium or laudanum or morphine may be used in some cases of severe diarrheal
diseases, e.g. cholera); also diarrhea secondary to Irritable Bowel Syndrome (Codeine,
paregoric, diphenoxylate, difenoxin, loperamide, laudanum)
 Anxiety due to shortness of breath (oxymorphone and dihydrocodeine only)
 Opioid dependence (methadone and buprenorphine only)
In the U.S., doctors virtually never prescribe opioids for psychological relief (with the narrow
exception of anxiety due to shortness of breath), despite their extensively reported
psychological benefits, and the widespread use of opiates in depression and anxiety up until the
mid 1950s. There are virtually no exceptions to this practice, even in circumstances where
researchers have reported opioids to be especially effective and where the possibility of
addiction or diversion is very low—for example, in the treatment of senile dementia, geriatric
depression, and psychological distress due to chemotherapy or terminal diagnosis.
Opioids are often used in combination with adjuvant analgesics (drugs which have an indirect
effect on the pain). In palliative care, opioids are not recommended for sedation or anxiety

because experience has found them to be ineffective agents in these roles. Some opioids are
relatively contraindicated in renal failure because of the accumulation of the parent drug or
their active metabolites (e.g. morphine and oxycodone). Age (young or old) is not a
contraindication to strong opioids. Some synthetic opioids such as pethidine have metabolites
which are actually neurotoxic and should therefore be used only in acute situations.
History
Non-clinical use was criminalized in the U.S by the Harrison Narcotics Tax Act of 1914, and by
other laws worldwide. Since then, nearly all non-clinical use of opioids has been rated zero on
the scale of approval of nearly every social institution. However, in United Kingdom the 1926
report of the Departmental Committee on Morphine and Heroin Addiction under the
Chairmanship of the President of the Royal College of Physicians reasserted medical control and
established the "British system" of control—which lasted until the 1960s; in the U.S. the
Controlled Substances Act of 1970 markedly relaxed the harshness of the Harrison Act.
Before the twentieth century, institutional approval was often higher, even in Europe and
America. In some cultures, approval of opioids was significantly higher than approval of alcohol.
Global shortage of poppy-based medicines
Morphine and other poppy-based medicines have been identified by The World Health
Organization as essential in the treatment of severe pain. However, only six countries use 77%
of the world's morphine supplies, leaving many emerging countries lacking in pain relief
medication. The current system of supply of raw poppy materials to make poppy-based
medicines is regulated by the International Narcotics Control Board under the provision of the
1961 Single Convention on Narcotic Drugs. The amount of raw poppy materials that each
country can demand annually based on these provisions must correspond to an estimate of the
country's needs taken from the national consumption within the preceding two years. In many
countries, underprescription of morphine is rampant because of the high prices and the lack of
training in the prescription of poppy-based drugs. The World Health Organization is now
working with different countries' national administrations to train healthworkers and to
develop national regulations regarding drug prescription to facilitate a greater prescription of
poppy-based medicines.
Another idea to increase morphine availability is proposed by the Senlis Council, who suggest,
through their proposal for Afghan Morphine, that Afghanistan could provide cheap pain relief
solutions to emerging countries as part of a second-tier system of supply that would
complement the current INCB regulated system by maintaining the balance and closed system
that it establishes while providing finished product morphine to those suffering from severe
pain and unable to access poppy-based drugs under the current system.

Adverse effects
Common adverse reactions in patients taking opioids for pain relief include: nausea and
vomiting, drowsiness, itching, dry mouth, miosis, and constipation.
Infrequent adverse reactions in patients taking opioids for pain relief include: dose-related
respiratory depression (especially with more potent opioids), confusion, hallucinations,
delirium, urticaria, hypothermia, bradycardia/tachycardia, orthostatic hypotension, dizziness,
headache, urinary retention, ureteric or biliary spasm, muscle rigidity, myoclonus (with high
doses), and flushing (due to histamine release, except fentanyl and remifentanil).
Opioid-induced hyperalgesia has been observed in some patients, whereby individuals using
opioids to relieve pain may paradoxically experience more pain as a result of their medication.
This phenomenon, although uncommon, is seen in some palliative care patients, most often
when dose is escalated rapidly. If encountered, rotation between several different opioid
analgesics may mitigate the development of hyperalgesia.
Both therapeutic and chronic use of opioids can compromise the function of the immune
system. Opioids decrease the proliferation of macrophage progenitor cells and lymphocytes,
and affect cell differentiation (Roy & Loh, 1996). Opioids may also inhibit leukocyte migration.
However the relevance of this in the context of pain relief is not known.
Men who are taking moderate to high doses of an opioid analgesic long-term are likely to have
subnormal testosterone levels, which can lead to osteoporosis and decreased muscle strength
if left untreated. Therefore, total and free testosterone levels should be monitored in these
patients; if levels are suboptimal, testosterone replacement therapy, preferably with patches or
transdermal preparations, should be given. Also, prostate-specific antigen levels should be
monitored.
Treating opioid adverse effects
Nausea: tolerance occurs within 7–10 days, during which antiemetics (e.g. low dose haloperidol
1.5–3 mg once at night) are very effective.[ Due to severe side effects such as tardive
dyskinesia, haloperidol is currently rarely used. A related drug, Compazine (prochlorperazine) is
more often used, although it has similar risks. (Stronger antiemetics such as ondansetron or
tropisetron may be indicated if nausea is severe or continues for an extended period, although
these tend to be avoided due to their high cost unless nausea is really problematic. A cheaper
alternative is dopamine antagonists, e.g. domperidone and metoclopramide. Domperidone
does not cross the blood-brain barrier, so blocks opioid emetic action in the chemoreceptor
trigger zone without adverse central anti-dopaminergic effects (not available in the U.S.) Some
antihistamines with anti-cholinergic properties (e.g. orphenadrine or diphenhydramine) may
also be effective. The first-generation anti-histamine hydroxyzine is very commonly used, with
the added advantages of not causing movement disorders, and also possessing analgesic-
sparing properties.

 5-HT3 antagonists (e.g. ondansetron)
 Dopamine antagonists (e.g. domperidone)
 Anti-cholinergic antihistamines (e.g. diphenhydramine)
Vomiting: this is due to gastric stasis (large volume vomiting, brief nausea relieved by vomiting,
oesophageal reflux, epigastric fullness, early satiation), besides direct action on the vomiting
centre of the brain. Vomiting can thus be prevented by prokinetic agents (e.g. domperidone or
metoclopramide 10 mg every eight hours). If vomiting has already started, these drugs need to
be administered by a non-oral route (e.g. subcutaneous for metoclopramide, rectally for
domperidone).
 Prokinetic agents (e.g. domperidone)

 Anti-cholinergic agents (e.g. orphenadrine)
Drowsiness: tolerance usually develops over 5–7 days, but if troublesome, switching to an
alternative opioid often helps. Certain opioids such as morphine and diamorphine (heroin) tend
to be particularly sedating, while others such as oxycodone and meperidine (pethidine) tend to
produce less sedation, but individual patients responses can vary markedly and some degree of
trial and error may be needed to find the most suitable drug for a particular patient. Treatment
is at any rate possible - CNS stimulants are generally effective.
 Stimulants (e.g. caffeine, modafinil, amphetamine)
Itching: tends not to be a severe problem when opioids are used for pain relief, but if required
then antihistamines are useful for counteracting itching. Non-sedating antihistamines such as
fexofenadine are preferable so as to avoid increasing opioid induced drowsiness, although
some sedating antihistamines such as orphenadrine may be helpful as they produce a
synergistic analgesic effect which allows smaller doses of opioids to be used while still
producing effective analgesia. For this reason some opioid/antihistamine combination products
have been marketed, such as Meprozine (meperidine/promethazine) and Diconal
(dipipanone/cyclizine), which may also have the added advantage of reducing nausea as well.
 Antihistamines (e.g. fexofenadine)
Constipation: develops in 99% of patients[on opioids and since tolerance to this problem does
not develop, nearly all patients on opioids will need a laxative. Over 30 years experience in
palliative care has shown that most opioid constipation can be successfully prevented:
"Constipation ... is treated [with laxatives and stool-softeners]" (Burton 2004, 277). According
to Abse, "It is very important to watch out for constipation, which can be severe" and "can be a
very considerable complication" (Abse 1982, 129) if it is ignored. Peripherally acting opioid
antagonists such as alvimopan (Entereg) and methylnaltrexone (Relistor) have been found to
effectively relieve opioid induced constipation without affecting analgesia or triggering
withdrawal symptoms, although alvimopan is contraindicated in patients who have taken
opioids for more than seven days, is only FDA-approved for 15 doses or less, and may increase

risk of heart attack. For mild cases, a lot of water (around 1.5 L/day) and fiber might suffice (in
addition to the laxative and stool-softeners).
 Stool-softening and peristalsis-promoting laxatives (e.g. docusate in combination with

bisacodyl or senna).
 Peripherally-acting opioid antagonists (e.g. methylnaltrexone)
 High water intake and dietary fiber
For more severe and/or chronic cases, the drugs that are used work by not increasing
peristalsis, but by preventing water uptake in the intestine, leading to a softer stool with a
larger component of water, and, additionally, by acidifying the environment inside the
intestine, which both decreases water uptake and enhances peristalsis (e.g. lactulose, which is
controversially noted as a possible probiotic). The following drugs are generally efficacious:
 Polyethylene glycol 3350±10% dalton powder for solution (MiraLax, GlycoLax) 8.5-34g
daily.
 Lactulose syrup 10g/15mL 30-45mL twice daily.
One medicine provider, Napp, claim to have solved this problem by combining Oxicodone with
an opioid suppressor, Naloxone, in a form which does not pass through the body-brain barrier.
Thus, the constipation effect is suppressed, but not the pain reduction. Their product is
marketed under the names Targiniq or Targinact.
Respiratory depression: although this is the most serious adverse reaction associated with
opioid use it usually is seen with the use of a single, intravenous dose in an opioid-naive
patient. In patients taking opioids regularly for pain relief, tolerance to respiratory depression
occurs rapidly, so that it is not a clinical problem. Several drugs have been developed which can
block respiratory depression completely even from high doses of potent opioids, without
affecting analgesia, although the only respiratory stimulant currently approved for this purpose
is doxapram, which has only limited efficacy in this application. Newer drugs such as BIMU-8
and CX-546 may however be much more effective.
 Respiratory stimulants: carotid chemoreceptor agonists (e.g. doxapram), 5-HT4 agonists

(e.g. BIMU8), δ-opioid agonists (e.g. BW373U86)
 Opioid antagonists (e.g. naloxone)
Finally, all opioid effects (adverse or otherwise) can readily be reversed with an opioid
antagonist (more exactly, an inverse agonist) such as naloxone or naltrexone. These
competitive antagonists bind to the opioid receptors with higher affinity than agonists but do
not activate the receptors. This displaces the agonist, attenuating and/or reversing the agonist
effects. However, the elimination half-life of naloxone can be shorter than that of the opioid
itself, so repeat dosing or continuous infusion may be required, or a longer acting antagonist
such as nalmefene may be used. In patients taking opioids regularly it is essential that the
opioid is only partially reversed to avoid a severe and distressing reaction of waking in

excruciating pain. This is achieved by not giving a full dose (e.g. naloxone 400 μg) but giving this
in small doses (e.g. naloxone 40 μg) until the respiratory rate has improved. An infusion is then
started to keep the reversal at that level, while maintaining pain relief.
Safety
Studies over the past 20 years have repeatedly shown opioids to be safe when they are used
correctly. In the UK two studies have shown that double doses of bedtime morphine did not
increase overnight deaths, and that sedative dose increases were not associated with
shortened survival (n=237). Another UK study showed that the respiratory rate was not
changed by morphine given for breathlessness to patients with poor respiratory function
(n=15). In Australia, no link was found between doses of opioids, benzodiazepines or
haloperidol and survival. In Taiwan, a study showed that giving morphine to treat
breathlessness on admission and in the last 48 hours did not affect survival. The survival of
Japanese patients on high dose opioids and sedatives in the last 48 hours was the same as
those not on such drugs.[25] In U.S. patients whose ventilators were being withdrawn, opioids
did not speed death, while benzodiazepines resulted in longer survival (n=75). Morphine given
to elderly patients in Switzerland for breathlessness showed no effect on respiratory function
(n=9, randomised controlled trial). Injections of morphine given subcutaneously to Canadian
patients with restrictive respiratory failure did not change their respiratory rate, respiratory
effort, arterial oxygen level, or end-tidal carbon dioxide levels. Even when opioids are given
intravenously, respiratory depression is not seen.
Carefully titrating the dose of opioids can provide for effective pain relief while minimizing
adverse effects. Morphine and diamorphine have been shown to have a wider therapeutic
range or "safety margin" than some other opioids. It is impossible to tell which patients need
low doses and which need high doses, so all have to be started on low doses, unless changing
from another strong opioid.
Opioid analgesics do not cause any specific organ toxicity, unlike many other drugs, such as
aspirin and acetaminophen. They are not associated with upper gastrointestinal bleeding and
renal toxicity.
Tolerance
Tolerance is the process whereby neuroadaptation occurs (through receptor desensitization)

resulting in reduced drug effects. Tolerance is more pronounced for some effects than for
others; tolerance occurs quickly to the effects on mood, itching, urinary retention, and
respiratory depression, but occurs more slowly to the analgesia and other physical side effects.
However, tolerance does not develop to constipation or miosis (the constriction of the pupil of
the eye to less than or equal to two millimeters).Tolerance to opioids is attenuated by a
number of substances, including:
 calcium channel blockers

 intrathecal magnesium and zinc
 NMDA antagonists, such as dextromethorphan or ketamine
 cholecystokinin antagonists, such as proglumide
 Newer agents such as the phosphodiesterase inhibitor ibudilast have also been
researched for this application.
Magnesium and zinc deficiency speed up the development of tolerance to opioids and relative
deficiency of these minerals is quite common due to low magnesium/zinc content in food and
use of substances which deplete them including diuretics (such as alcohol,
caffeine/theophylline) and smoking. Reducing intake of these substances and taking
zinc/magnesium supplements may slow the development of tolerance to opiates.
Dependence
Dependence is characterised by extremely unpleasant withdrawal symptoms that occur if

opioid use is abruptly discontinued after tolerance has developed. The withdrawal symptoms
include severe dysphoria, sweating, nausea, rhinorrea, depression, severe fatigue, vomiting and
pain. Slowly reducing the intake of opioids over days and weeks will reduce or eliminate the
withdrawal symptoms. The speed and severity of withdrawal depends on the half-life of the
opioid; heroin and morphine withdrawal occur more quickly and are more severe than
methadone withdrawal, but methadone withdrawal takes longer. The acute withdrawal phase
is often followed by a protracted phase of depression and insomnia that can last for months.
The symptoms of opioid withdrawal can also be treated with other medications, such as
clonidine, antidepressants and benzodiazepines, but with a low efficacy.
Addiction
Addiction is the process whereby physical and/or psychological dependence develops to a drug
- including opioids. The withdrawal symptoms can reinforce the addiction, driving the user to
continue taking the drug. Psychological addiction is more common in people taking opioids
recreationally.
Misuse
Drug misuse is the use of drugs for reasons other than what the drug was prescribed for.
Opioids are primarily misused due to their ability to produce euphoria.

Examples
Endogenous opioids
Opioid-peptides that are produced in the body include:
 Endorphins
 Enkephalins
 Dynorphins
 Endomorphins
β-endorphin is expressed in Pro-opiomelanocortin (POMC) cells in the arcuate nucleus and in a

small population of neurons in the brainstem, and acts through μ-opioid receptors. β-endorphin
has many effects, including on sexual behavior and appetite. β-endorphin is also secreted into
the circulation from pituitary corticotropes and melanotropes. α-neoendorphin is also
expressed in POMC cells in the arcuate nucleus.
[met]-enkephalin is widely distributed in the CNS; [met]-enkephalin is a product of the

proenkephalin gene, and acts through μ and δ-opioid receptors. [leu]-enkephalin, also a
product of the proenkephalin gene, acts through δ-opioid receptors.
Dynorphin acts through κ-opioid receptors, and is widely distributed in the CNS, including in the
spinal cord and hypothalamus, including in particular the arcuate nucleus and in both oxytocin
and vasopressin neurons in the supraoptic nucleus.
Endomorphin acts through μ-opioid receptors, and is more potent than other endogenous
opioids at these receptors.
Opium alkaloids
Phenanthrenes naturally occurring in opium:
 Codeine
 Morphine
 Thebaine, Oripavine

1) 3-methylation produce codeine (3-methyl morphine)
Morphine
CH3
2) 3,6-dimethylation produce thiabaine (3,6-dimethyl morphine)
1
N
10 17
2 11 16
9
3) 3,6-diacetyl morphine is known as heroin
15 4) 7,8-dihydro-6-keto morphine is hydromorphone
3
12 14 8
HO 4 13
5) 7,8-dihydro-6-keto-14 hydroxy morphine is oxomorphone
O 7
5 6) N-allyl-7,8-dihydro-6-keto-14 hydroxy normorphine is naloxone
6
OH
N-cyclopropyl methyl-7,8-dihydro-6-keto-14 hydroxy normorphine (Naltreoxone)
SAR (Structure Activity relationship) of morphine
1. If 3-hydroxyl group is replaced by 3-H, activity decrease ten times

2. If 3-hydroxyl group is replaced by 3-methoxy group, analgesic activity decrease
but compound becomes anti-tussive (codeine)
3. If 3-hydroxyl group is replaced by 3-acetyl group, activity decrease.
4. If 6-hydroxyl group is replaced by 6-acetyl group, activity increase ten times
5. If 7,8 double bound is reduced and 6-hydroxy is oxidized to keto group then
activity increase 8 to 10 times (hydromorphone)
6. If 14-position of morphine is hydroxylated, activity increase (oxomorphome)
7. If basic nitrogen contains methyl then the drug is agonist on µ receptor
(morphine) but methyl is replace by 3 – 5 carbon aliphatic or carbocyclic group
compound becomes antagonist at µ receptor (Naloxone, naltreoxone) but k
receptor agonist (pentazocin, nalbupine, butorphanol), when chain is increased
8-10 carbon then the compound becomes again µ receptor agonist (Fentanyl).
Preparations of mixed opium alkaloids, including papaveretum, are still occasionally

used.Semisynthetic derivatives
 Diacetylmorphine (heroin)
 Dihydrocodeine
 Hydrocodone
 Hydromorphone
 Nicomorphine
 Oxycodone
 Oxymorphone
Synthetic opioids
Anilidopiperidines
 Fentanyl

 Alphamethylfentanyl
 Alfentanil
 Sufentanil
 Remifentanil
 Carfentanyl
 Ohmefentanyl
Phenylpiperidines
 Pethidine (meperidine)
 Ketobemidone
 MPPP
 Allylprodine
 Prodine
 PEPAP
Diphenylpropylamine derivatives
 Propoxyphene
 Dextropropoxyphene
 Dextromoramide
 Bezitramide
 Piritramide
 Methadone
 Dipipanone
 Levomethadyl Acetate (LAAM)
 Difenoxin
 Diphenoxylate
 Loperamide (used for diarrhoea, does not cross the blood-brain barrier)
Benzomorphan derivatives
 Dezocine - agonist/antagonist
 Pentazocine - agonist/antagonist
 Phenazocine
[edit] Oripavine derivatives
 Buprenorphine - partial agonist

 Dihydroetorphine
 Etorphine
Morphinan derivatives

 Butorphanol - agonist/antagonist
 Nalbuphine - agonist/antagonist
 Levorphanol
 Levomethorphan
Morphinans
CH3
If D ring in morphine is removed or k agonist mu antantagonist
N
(epoxide) the remaining 4 ring skelton is Butorphanol
1
N
10 17
1 10 17 known as morphinans (Levorphanol). leavo 2 11 16
2 11 16 9
9 form of morphinan acts as analgesic but 15 OH
A B E15 dextroform shows anti-tussive activity like 3
3 8
12 14
HO
12
13
14 8 Dextromethorphan (dextro rotatary methyl HO 4 13
4
form of levorphanol)
5 7
Levorphanol 5 C 7
6
6
Others
 Lefetamine
 Meptazinol
 Tilidine
 Tramadol
 Tapentadol
CH3 CH3
Meperidine Fentanyl
6,7-Benzmorphane N CH3 COOEt
H3C N N
N O
CH3
HO
Pentazocine CH3
ethyl 1-methyl-4-phenylpiperidine-4-carboxylate
2,6 metheno-3-benzazocine
O Tramadol CH3
Methadone CH3 N
H3C
CH3
H3C N H3CO
HO
H3C
Opioid antagonists
 Nalmefene
 Naloxone
 Naltrexone

ANTIPSYCHOTIC
An antipsychotic (or neuroleptic) is a tranquilizing psychiatric medication primarily used to
manage psychosis (including delusions or hallucinations, as well as disordered thought),
particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as
typical antipsychotics, was discovered in the 1950s. Most of the drugs in the second generation,
known as atypical antipsychotics, have been developed more recently, although the first
atypical antipsychotic, clozapine, was discovered in the 1950s and introduced clinically in the
1970s. Both generations of medication tend to block receptors in the brain's dopamine
pathways, but antipsychotic drugs encompass a wide range of receptor targets.
A number of harmful and undesired (adverse) effects have been observed, including lowered
life expectancy, weight gain, enlarged breasts and milk discharge in men and women
(hyperprolactinaemia), lowered white blood cell count (agranulocytosis), involuntary repetitive
body movements (tardive dyskinesia), diabetes, an inability to sit still or remain motionless
(akathisia), sexual dysfunction, a return of psychosis requiring increasing the dosage due to cells
producing more neurochemicals to compensate for the drugs (tardive psychosis), and a
potential for permanent chemical dependence leading to psychosis much worse than before
treatment began, if the drug dosage is ever lowered or stopped (tardive dysphrenia).
Temporary withdrawal symptoms including insomnia, agitation, psychosis, and motor disorders
may occur during dosage reduction of antipsychotics, and can be mistaken for a return of the
underlying condition.
The development of new antipsychotics with fewer of these adverse effects and with greater
relative effectiveness as compared to existing antipsychotics (efficacy), is an important ongoing
field of research. The most appropriate drug for an individual patient requires careful
consideration.
History
The original antipsychotic drugs were happened upon largely by chance and then tested for
their effectiveness. The first, chlorpromazine, was developed as a surgical anesthetic. It was
first used on psychiatric patients because of its powerful calming effect; at the time it was
regarded as a "chemical lobotomy". Lobotomy at the time was used to treat many behavioral
disorders, including psychosis, although its effect was to markedly reduce behavior and mental
functioning of all types. However, chlorpromazine proved to reduce the effects of psychosis in a
more effective and specific manner than the extreme lobotomy-like sedation it was known for.
The underlying neurochemistry involved has since been studied in detail, and subsequent
antipsychotic drugs have been discovered by an approach that incorporates this sort of
information.
Antipsychotics have long been known as neuroleptic drugs. The word neuroleptic was derived
from the Greek: "νεῦρον" (neuron, originally meaning "sinew" but today referring to the
nerves) and "λαμβάνω" (lambanō, meaning "take hold of"). Thus, the word means taking hold
of one's nerves. This may refer to common side effects such as reduced activity, lethargy, and
impaired motor control. Although these effects are unpleasant and in some cases harmful, they
were at one time considered a reliable sign that the drug was working. The term "neuroleptic"
is being abandoned in favor of "antipsychotic," which refers to the drug's desired effects.
Typical antipsychotics have also been referred to as the major tranquilizers, because of their
tendency to tranquilize and sedate. As with the term "neuroleptics," the term "major
tranquilizers" is falling out of common and scientific use. The term "tranquilizers" now generally
refers to drugs that are primarily intended to sedate—mostly the barbiturates and
benzodiazepines, which were once referred to as the "minor tranquilizers."
Antipsychotics are broadly divided into two groups, the typical or first-generation
antipsychotics and the atypical or second-generation antipsychotics. The typical antipsychotics
are classified according to their chemical structure while the atypical antipsychotics are
classified according to their pharmacological properties. These include serotonin-dopamine
antagonists (see dopamine antagonist and serotonin antagonist), multi-acting receptor-
targeted antipsychotics (MARTA, those targeting several systems), and dopamine partial
agonists, which are often categorized as atypicals.
Usage
Common conditions with which antipsychotics might be used include schizophrenia, bipolar
disorder and delusional disorder. Antipsychotics might also be used to counter psychosis
associated with a wide range of other diagnoses, such as psychotic depression. However, not all
symptoms require heavy medication and hallucinations and delusions should only be treated if
they distress the patient or produce dangerous behaviors.
In addition, "antipsychotics" are increasingly used to treat non-psychotic disorders. For

example, they are sometimes used off-label to manage aspects of Tourette syndrome or autism
spectrum disorders. They have multiple off-label uses as an augmentation agent (i.e. in addition
to another medication), for example in "treatment-resistant" depression or OCD. Despite the
name, the off-label use of "antipsychotics" is said to involve deploying them as antidepressants,
anti-anxiety drugs, mood stabilizers, cognitive enhancers, anti-aggressive, anti-impulsive, anti-
suicidal and hypnotic (sleep) medications.
Antipsychotics have also been increasingly used off-label in cases of dementia in older people,
and for various disorders and difficulties in children and teenagers. A survey of children with

pervasive developmental disorder found that 16.5% were taking an antipsychotic drug, most
commonly to alleviate mood and behavioral disturbances characterized by irritability,
aggression, and agitation. Recently, risperidone was approved by the US FDA for the treatment
of irritability in children and adolescents with autism.
Antipsychotics are sometimes used as part of compulsory treatment via inpatient (hospital)
commitment or outpatient commitment. This may involve various methods to persuade a
person to take the medication, or actual physical force. Administration may rely on an
injectable form of the drug rather than tablets. The injection may be of a long-lasting type
known as a depot injection, usually applied at the top of the buttocks.
Due to the chronic nature of the treated disorders, antipsychotic medications, once started, are
seldom discontinued, and the aim of the treatment is often to gradually reduce dosage to a
minimum safe maintenance dose that is enough to control the symptoms. Only when the side-
effects have become too severe and/or a patient have been symptom-free for a long periods of
time, is discontinuation carefully attempted. One reason for this strategy is that discontinuation
and restarting of neuroleptics tends to cause increasing nervous system malfunction, affecting
the brainstem and autonomous nervous system that control vital body functions.
Side-effects
Antipsychotics are associated with a range of side effects. It is well-recognized that many
people stop taking them (around two-thirds even in controlled drug trials) due in part to
adverse effects. Extrapyramidal reactions include acute dystonias, akathisia, parkinsonism
(rigidity and tremor), tardive dyskinesia, tachycardia, hypotension, impotence, lethargy,
seizures, intense dreams or nightmares, and hyperprolactinaemia. Some of the side-effects will
appear after the drug has been used only for a long time.
The most serious adverse effect associated with long-term antipsychotic use is lowered life
expectancy. This has proved most controversial in regard to the use of antipsychotics in
dementia in older people, worsened by alleged use to control and sedate rather than
necessarily to treat. A 2009 systematic review of studies of schizophrenia also found decreased
life expectancy associated with use of antipsychotics and argued that more studies were
urgently needed, a call that had already been made when similar results were found in 2006.
In "healthy" individuals without psychosis, doses of antipsychotics can produce the so-called
"negative symptoms" (e.g. emotional and motivational difficulties) associated with
schizophrenia.
From a subjective perspective, antipsychotics heavily influence one's perceptions of pleasurable

sensations, causing a severe reduction in feelings of desire, motivation, pensive thought, and
awe. This does not coincide with the apathy and lack of motivation experienced by the negative
symptoms of schizophrenia. Detrimental effects on short term memory, which affect the way
one figures and calculates (although this also may be purely subjective), may also be observed

on high enough dosages. These are all the reasons why they are thought to affect "creativity".
Also, for some individuals with schizophrenia, too much stress may cause "relapse".
Following are details concerning some of the side effects of antipsychotics:
 Antipsychotics, particularly atypicals, appear to cause diabetes mellitus and fatal

diabetic ketoacidosis, especially (in US studies) in African Americans.
 Antipsychotics may cause pancreatitis.
 The atypical antipsychotics (especially olanzapine) seem to cause weight gain more
commonly than the typical antipsychotics. The well-documented metabolic side effects
associated with weight gain include diabetes, which can be life-threatening.
 Antipsychotics increase the likelihood of a fatal heart attack, with the risk of death
increasing with dose and the length of time on the drug.
 Clozapine also has a risk of inducing agranulocytosis, a potentially dangerous reduction
in the number of white blood cells in the body. Because of this risk, patients prescribed
clozapine may need to have regular blood checks to catch the condition early if it does
occur, so the patient is in no danger.
 One of the more serious of these side effects is tardive dyskinesia, in which the sufferer
may show repetitive, involuntary, purposeless movements often of the lips, face, legs,
or torso. It is believed that there is a greater risk of developing tardive dyskinesia with
the older, typical antipsychotic drugs, although the newer antipsychotics are now also
known to cause this disorder.
 A potentially serious side effect of many antipsychotics is that they tend to lower an
individual's seizure threshold. Chlorpromazine and clozapine, in particular, have a
relatively high seizurogenic potential. Fluphenazine, haloperidol, pimozide and
risperidone exhibit a relatively low risk. Caution should be exercised in individuals that
have a history of seizurogenic conditions such as epilepsy, or brain damage.
 Neuroleptic malignant syndrome, in which the drugs appear to cause the temperature
regulation centers to fail, resulting in a medical emergency, as the patient's temperature
suddenly increases to dangerous levels.
 Dysphoria.
 Sexual dysfunction, which may rarely continue after withdrawal, similar to Post-SSRI
sexual dysfunction (PSSD).
 Dystonia, a neurological movement disorder in which sustained muscle contractions
cause twisting and repetitive movements or abnormal postures.
 Hyperprolactinaemia. The breasts may enlarge and discharge milk, in both men and
women due to abnormally-high levels of prolactin in the blood. Prolactin secretion in
the pituitary is normally suppressed by dopamine. Drugs that block the effects of
dopamine at the pituitary or deplete dopamine stores in the brain may cause the
pituitary to secrete prolactin.
 There is evidence that exposure may cause demyelinating disease in laboratory animals.
 Following controversy over possible increased mortality (death) related to
antipsychotics in indivdiuals with dementia, warnings have been added to packaging.

Continuous use of neuroleptics has been shown to decrease the total brain volume by 10% in
macaque monkeys.
Some people suffer few apparent side effects from taking antipsychotic medication, whereas
others may have serious adverse effects. Some side effects, such as subtle cognitive problems,
may go unnoticed.
There is a possibility that the risk of tardive dyskinesia can be reduced by combining the anti-
psychotics with diphenhydramine or benzatropine, although this remains to be established.
Central nervous system damage is also associated with irreversible tardive akathisia and/or
tardive dysphrenia.
Withdrawal
Withdrawal symptoms from antipsychotics may emerge during dosage reduction and
discontinuation. Withdrawal symptoms can include nausea, emesis, anorexia, diarrhea,
rhinorrhea, diaphoresis, myalgia, paresthesia, anxiety, agitation, restlessness, and insomnia.
The psychological withdrawal symptoms can include psychosis, and can be mistaken for a
relapse of the underlying disorder. Conversely, the withdrawal syndrome may also be a trigger
for relapse. Better management of the withdrawal syndrome may improve the ability of
individuals to discontinue antipsychotics.
Tardive dyskinesia can emerge as a physical withdrawal symptom, and may either gradually
abate during the withdrawal phase, or become persistent. Withdrawal-related psychosis from
antipsychotics is called "supersensitivity psychosis", and is attributed to increased number and
sensitivity of brain dopamine receptors, due to blockade of dopaminergic receptors by the
antipsychotics, which often leads to exacerbated symptoms in the absence of neuroleptic
medication. Efficacy of antipsychotics may likewise be reduced over time, due to this
development of drug tolerance.
Withdrawal effects may also occur when switching a person from one antipsychotic to another,
(presumably due to variations of potency and receptor activity). Such withdrawal effects can
include cholinergic rebound, an activation syndrome, and motor syndromes including
dyskinesias. These adverse effects are more likely during rapid changes between antipsychotic
agents, so making a gradual change between antipsychotics minimises these withdrawal
effects. The British National Formulary recommends a gradual withdrawal when discontinuing
antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.
Efficacy
There have been a large number of studies of the efficacy of typical antipsychotics, and an
increasing number on the more recent atypical antipsychotics.

The American Psychiatric Association and the UK National Institute for Health and Clinical
Excellence recommend antipsychotics for managing acute psychotic episodes in schizophrenia
or bipolar disorder, and as a longer-term maintenance treatment for reducing the likelihood of
further episodes. They state that response to any given antipsychotic can be variable so that
trials may be necessary, and that lower doses are to be preferred where possible. A number of
studies have looked at levels of "compliance" or "adherence" with antipsychotic regimes and
found that discontinuation (stopping taking them) by patients is associated with higher rates of
relapse, including hospitalization.
Nevertheless, a 2009 systematic review and meta-analysis of trials in people diagnosed with
schizophrenia found that less than half (41%) showed any therapeutic response to an
antipsychotic, compared to 24% on placebo, and that there was a decline in treatment
response over time, and possibly a bias in which trial results were published. In addition, a 2010
Cochrane Collaboration review of trials of Risperidone, one of the biggest selling antipsychotics
and the first of the new generation to become available in generic form, found only marginal
benefit compared with placebo and that, despite its widespread use, evidence remains limited,
poorly reported and probably biased in favor of risperidone due to pharmaceutical company
funding of trials. Another Cochrane review in 2009, of bipolar disorder, found the efficacy and
risk/benefit ratio better for the traditional mood stabilizer lithium than for the antipsychotic
Olanzapine as a first line maintenance treatment.
Antipsychotic polypharmacy (prescribing two or more antipsychotics at the same time for an
individual) is said to be a common practice but not necessarily evidence-based or
recommended, and there have been initiatives to curtail it. Similarly, the use of excessively high
doses (often the result of polypharmacy) continues despite clinical guidelines and evidence
indicating that it is usually no more effective but is usually more harmful.
A review by the US Agency for Healthcare Research and Quality found that much of the
evidence for the off-label use of antipsychotics (for example, for depression, dementia, OCD,
PTSD, Personality Disorders, Tourette's) was of insufficient scientific quality to support such
use, especially as there was strong evidence of increased risks of stroke, tremors, significant
weight gain, sedation, and gastrointestinal problems. A UK review of unlicensed usage in
children and adolescents reported a similar mixture of findings and concerns.
Aggressive challenging behavior in adults with intellectual disability is often treated with
antipsychotic drugs despite lack of an evidence base. A recent randomized controlled trial,
however, found no benefit over placebo and recommended that the use of antipsychotics in
this way should no longer be regarded as an acceptable routine treatment.
A 2006 Cochrane Collaboration review of controlled trials of antipsychotics in old age dementia
reported that one or two of the drugs showed a modest benefit compared to placebo in
managing aggression or psychosis, but that this was combined with a significant increase in
serious adverse events. They concluded that this confirms that antipsychotics should not be

used routinely to treat dementia patients with aggression or psychosis, but may be an option in
the minority of cases where there is severe distress or risk of physical harm to others.
Some doubts have been raised about the long-term effectiveness of antipsychotics for
schizophrenia, in part because two large international World Health Organization studies found
individuals diagnosed with schizophrenia tend to have better long-term outcomes in developing
countries (where there is lower availability and use of antipsychotics and mental health
problems are treated with more informal, community-led methods only) than in developed
countries. The reasons for the differences are not clear, however, and various explanations
have been suggested.
Some argue that the evidence for antipsychotics from discontinuation-relapse studies may be
flawed, because they do not take into account that antipsychotics may sensitize the brain and
provoke psychosis if discontinued, which may then be wrongly interpreted as a relapse of the
original condition. Evidence from comparison studies indicates that at least some individuals
with schizophrenia recover from psychosis without taking antipsychotics, and may do better in
the long term than those that do take antipsychotics. Some argue that, overall, the evidence
suggests that antipsychotics only help if they are used selectively and are gradually withdrawn
as soon as possible and have referred to the "Myth of the antipsychotic".
A review of the methods used in trials of antipsychotics, despite stating that the overall quality
is "rather good," reported issues with the selection of participants (including that in
schizophrenia trials up to 90% of people who are generally suitable do not meet the elaborate
inclusion and exclusion criteria, and that negative symptoms have not been properly assessed
despite companies marketing the newer antipsychotics for these); issues with the design of
trials (including pharmaceutical company funding of most of them, and inadequate
experimental "blinding" so that trial participants could sometimes tell whether they were on
placebo or not); and issues with the assessment of outcomes (including the use of a minimal
reduction in scores to show "response," lack of assessment of quality of life or recovery, a high
rate of discontinuation, selective highlighting of favorable results in the abstracts of
publications, and poor reporting of side-effects).
Typicals versus atypicals
While the atypical (second-generation) antipsychotics were marketed as offering greater

efficacy in reducing psychotic symptoms while reducing side effects (and Extrapyramidal
symptoms in particular) than typical medications, the results showing these effects often lacked
robustness, and the assumption was increasingly challenged even as atypical prescriptions were
soaring. One review concluded there were no differences while another found that atypicals
were "only moderately more efficacious". These conclusions were, however, questioned by
another review, which found that clozapine, amisulpride, and olanzapine and risperidone were
more effective Clozapine has appeared to be more effective than other atypical antipsychotics,
although it has previously been banned due to its potentially lethal side effects. While
controlled clinical trials of atypicals reported that extrapyramidal symptoms occurred in 5–15%

of patients, a study of bipolar disorder in a real world clinical setting found a rate of 63%,
questioning the generalizability of the trials.
In 2005 the US government body NIMH published the results of a major independent (not
funded by the pharmaceutical companies) multi-site, double-blind study (the CATIE project).
This study compared several atypical antipsychotics to an older typical antipsychotic,
perphenazine, among 1493 persons with schizophrenia. The study found that only olanzapine
outperformed perphenazine in discontinuation rate (the rate at which people stopped taking it
due to its effects). The authors noted an apparent superior efficacy of olanzapine to the other
drugs in terms of reduction in psychopathology and rate of hospitalizations, but olanzapine was
associated with relatively severe metabolic effects such as a major weight gain problem
(averaging 44 pounds over 18 months) and increases in glucose, cholesterol, and triglycerides.
The mean and maximal doses used for olanzapine were considerably higher than standard
practice, and this has been postulated as a biasing factor that may explain olanzapine's superior
efficacy over the other atypical antipsychotics studied, where doses were more in line with
clinically relevant practices. No other atypical studied (risperidone, quetiapine, and ziprasidone)
did better than the typical perphenazine on the measures used, nor did they produce fewer
adverse effects than the typical antipsychotic perphenazine (a result supported by a meta-
analysis by Dr. Leucht published in Lancet), although more patients discontinued perphenazine
owing to extrapyramidal effects compared to the atypical agents (8% vs. 2% to 4%, P=0.002).
A phase 2 part of this CATIE study roughly replicated these findings. This phase consisted of a
second randomization of the patients that discontinued taking medication in the first phase.
Olanzapine was again the only medication to stand out in the outcome measures, although the
results did not always reach statistical significance (which means they were not reliable
findings) due in part to the decrease of power. The atypicals again did not produce fewer
extrapyramidal effects than perphenazine. A subsequent phase was conducted that allowed
clinicians to offer clozapine which was more effective at reducing medication drop-outs than
other neuroleptic agents. However, the potential for clozapine to cause toxic side effects,
including agranulocytosis, limits its usefulness.
It had been hoped that patient adherence to antipsychotics would be higher with the atypicals,
but a 2008 review found that the data have failed to substantiate the notion that novel
antipsychotic drug use leads to improved medication compliance and favorable clinical
outcomes.[62]
Overall evaluations of the CATIE and other studies have led many researchers to question the
first-line prescribing of atypicals over typicals, or even to question the distinction between the
two classes.[63][64] In contrast, other researchers point to the significantly higher risk of tardive
dyskinesia and EPS with the typicals and for this reason alone recommend first-line treatment
with the atypicals, notwithstanding a greater propensity for metabolic adverse effects in the
latter. The UK government organization NICE recently revised its recommendation favoring
atypicals, to advise that the choice should be an individual one based on the particular profiles
of the individual drug and on the patient's preferences.

The re-evaluation of the evidence has not necessarily slowed the bias towards prescribing the
atypicals, however.
Common antipsychotics
First generation antipsychotics (Typical antipsychotic)
Phenothiazines
 (Aliphatic Chain analogoues):- Chlorpromazine (Thorazine, Largactil), Promazine,

Triflupromazine (Vesprin) Levomepromazine (Nozinan), Promethazine (Phenergan)
 (Piperidinyl side chain analogoues):- Thioridazine (Mellaril, Melleril), Mesoridazine
 (Piperizinyl side chain analogoues):-Trifluoperazine (Stelazine), Fluphenazine (Prolixin) -
Available in decanoate (long-acting) form, Perphenazine (Trilafon), Prochlorperazine
(Compazine), Periciazine
 (Diphenyl butyl piperidine derivative):-Pimozide (Orap)
Butyrophenones
 Haloperidol (Haldol, Serenace), Droperidol (Droleptan)
Thioxanthenes
 Chlorprothixene (Cloxan, Taractan, Truxal), Clopenthixol (Sordinol), Flupenthixol

(Depixol, Fluanxol), Thiothixene (Navane), Zuclopenthixol (Cisordinol, Clopixol,
Acuphase)

Phenothiazine Derivatives Thioxanthene Derivatives
6 4 6 4
S S
7 5 3 7 5 3
2
Phenothiazine 2 Substituting C for
8 8
N R1 nucleus 10 R1 N in the nucleus
9 10 1 9 1
R R
Name R1 R Name R1 R
(Aliphatic side Chain) Chlorprothixene -Cl -CH2-CH2-CH2N(CH3)2

Chlorpromazine -Cl -CH2-CH2-CH2N(CH3)2 Thiothixene -SONH - CH2 CH2 CH2 N N CH3
2
Triflupromazine -CF3 -CH2-CH2-CH2N(CH3)2
(Piperidine side Chain)

Thioridazine -SCH3 - CH3 Butyrophenone
N
OH
F N
(Piperizine side Chain) O
Haloperidol Cl
Trifluoperzine -CF3 - CH2 CH2 CH2 N N CH3
Perphenazine -Cl - CH2 CH2 CH2 N N -CH 2CH 2OH Metabolic Product of phenothiazine
is 7-O-Glu-Nor-CPZ-SO
Fluphenazine -CF3 - CH2 CH2 CH2 N N -CH 2CH 2OH
Commonly used antipsychotic medications are listed above by drug group. Trade names appear
in parentheses.
SAR of Phenothiazines
1. 2-position is substituted by electron withdrawing groups like –Cl, CF3, SCH3 etc.
for antipsychotic activity.
2. Aliphatic side chain at 10-position must contain three carbon chain; lengthening
or shortening of the chain diminish neuroleptic activity.
3. Nitrogen in side chain must be tertiary for antipsychotic activity.
4. Piperidine, piperizine ring in side chain increase the potency of drugs.
Second generation antipsychotics (Atypical antipsychotic)
 Clozapine (Clozaril) - Requires weekly to biweekly complete blood count due to risk of
agranulocytosis.
 Olanzapine (Zyprexa) - Used to treat psychotic disorders including schizophrenia, acute
manic episodes, and maintenance of bipolar disorder. Dosing 2.5 to 20 mg per day.

F H
O C2H5 N
4 3
N O
O 5 2
CH3 N
6 N
7 H N
Molindone 1 CH3 CH3
N N
Pimozide
F
N N
9 N 1 9 N 1
10 11 Cl 10 11
8 Cl 2
Loxapine 2 Clozapine 8
7
O 3 N 3
5 7
6 4 6 H 4
5
O
N CH 2CH 2OCH2CH 2OH
N
N CH3
F
N N
N N
CH2 Quetiapine
O S
Risperidone
CH3
N
N
S
N N O
N
Olanzapine N N
Cl H
Ziprasidone
N CH3
S
H
Cl Cl
Third Generation compound
O
N N
OH
Aripiprazole N
H
Figure:- Structural formulas of some newer antipsychotic drugs (Second Generation)
 Risperidone (Risperdal) - Dosing 0.25 to 6 mg per day and is titrated upward; divided
dosing is recommended until initial titration is completed, at which time the drug can be
administered once daily. Used off-label to treat Tourette syndrome and anxiety
disorder.
 Quetiapine (Seroquel) - Used primarily to treat bipolar disorder and schizophrenia, and
"off-label" to treat chronic insomnia and restless legs syndrome; it is a powerful
sedative. Dosing starts at 25 mg and continues up to 800 mg maximum per day,
depending on the severity of the symptom(s) being treated.
 Ziprasidone (Geodon) - Approved in 2004 to treat bipolar disorder. Dosing 20 mg twice
daily initially up to 80 mg twice daily. Side-effects include a prolonged QT interval in the

heart, which can be dangerous for patients with heart disease or those taking other
drugs that prolong the QT interval.
 Amisulpride (Solian) - Selective dopamine antagonist. Higher doses (greater than
400 mg) act upon post-synaptic dopamine receptors resulting in a reduction in the
positive symptoms of schizophrenia, such as psychosis. Lower doses, however, act upon
dopamine autoreceptors, resulting in increased dopamine transmission, improving the
negative symptoms of schizophrenia. Lower doses of amisulpride have also been shown
to have antidepressant and anxiolytic effects in non-schizophrenic patients, leading to
its use in dysthymia and social phobias. Amisulpride has not been approved for use by
the Food and Drug Administration in the United States.
 Asenapine (Saphris) is a 5-HT2A- and D2-receptor antagonist under development for the
treatment of schizophrenia and acute mania associated with bipolar disorder.
 Paliperidone (Invega) - Derivative of risperidone that was approved in 2006.
 Iloperidone (Fanapt) - Approved by the FDA on May 6, 2009.
 Zotepine (Nipolept, Losizopilon, Lodopin, Setous)- An atypical antipsychotic indicated for
acute and chronic schizophrenia. It was approved in Japan circa 1982 and Germany in
1990, respectively.
 Sertindole (Serdolect, and Serlect in Mexico). Sertindole was developed by the Danish
pharmaceutical company H. Lundbeck. Like the other atypical antipsychotics, it is
believed to have antagonist activity at dopamine and serotonin receptors in the brain.
Third generation antipsychotics
 Aripiprazole (Abilify) - Dosing 1 mg up to maximum of 30 mg has been used. Mechanism

of action is thought to reduce susceptibility to metabolic symptoms seen in some other
atypical antipsychotics. The extent to which these effects differ from other atypical
antipsychotics is debated.
 Partial agonists of dopamine.
Other options
 Cannabidiol is one of the main components of Cannabis sativa. Cannabidiol differs from
the active drug in cannabis, tetrahydrocannabinol, in that cannabidiol lacks the typical
intoxicating and recreational effects. One study has suggested that cannabidiol may be
as effective as atypical antipsychotics in treating schizophrenia.[71] Some further
research has supported these results, and found fewer side effects with cannabidiol
than with amisulpride.
 Tetrabenazine is similar in function to antipsychotic drugs, though is not, in general,
considered an antipsychotic itself. Its main usefulness is the treatment of hyperkinetic
movement disorders such as Huntington's disease and Tourette syndrome, rather than
for conditions such as schizophrenia. Also, rather than having the potential to cause
tardive dyskinesia, which most antipsychotics have, tetrabenazine can be an effective
treatment for the condition.

 Metabotropic glutamate receptor 2 agonism has been seen as a promising strategy in
the development of novel antipsychotics. When tested in patients, the research
substance LY2140023 yielded promising results and had few side effects. The active
metabolite of this prodrug targets the brain glutamate receptors mGluR2/3 rather than
dopamine receptors.
 Glycine transporter 1 inhibition. RG1678 has been shown in phase 2 clinical trials to be
selectively effective for the negative symptoms of schizophrenia.
Drug action
All antipsychotic drugs tend to block D2 receptors in the dopamine pathways of the brain. This
means that dopamine released in these pathways has less effect. Excess release of dopamine in
the mesolimbic pathway has been linked to psychotic experiences. It is the blockade of
dopamine receptors in this pathway that is thought to control psychotic experiences.
Typical antipsychotics are not particularly selective and also block dopamine receptors in the
mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2
receptors in these other pathways is thought to produce some of the unwanted side effects
that the typical antipsychotics can produce (see below). They were commonly classified on a
spectrum of low potency to high potency, where potency referred to the ability of the drug to
bind to dopamine receptors, and not to the effectiveness of the drug. High-potency
antipsychotics such as haloperidol, in general, have doses of a few milligrams and cause less
sleepiness and calming effects than low-potency antipsychotics such as chlorpromazine and
thioridazine, which have dosages of several hundred milligrams. The latter have a greater
degree of anticholinergic and antihistaminergic activity, which can counteract dopamine-
related side effects.
Atypical antipsychotic drugs have a similar blocking effect on D2 receptors. Some also block or
partially block serotonin receptors (particularly 5HT2A, C and 5HT1A receptors):ranging from
risperidone, which acts overwhelmingly on serotonin receptors, to amisulpride, which has no
serotonergic activity. The additional effects on serotonin receptors may be why some of them
can benefit the "negative symptoms" of schizophrenia.
Structural effects
Many studies now indicate that chronic treatment with antipsychotics affects the brain at a
structural level, for example increasing the volume of the basal ganglia (especially the caudate
nucleus), and reducing cortical grey matter volume in different brain areas. The effects may
differ for typical versus atypical antipsychotics and may interact with different stages of
disorders. Death of neurons in the cerebral cortex, especially in women, has been linked to the
use of both typical and atypical antipsychotics for individuals with Alzheimers.
Recent studies on macaque monkeys have found that administration of haloperidol or

olanzapine for about two years led to a significant overall shrinkage in brain tissue, in both gray

and white matter across several brain areas, with lower glial cell counts, due to a decrease in
astrocytes and oligodendrocytes, and increased neuronal density. It has been said that these
studies require serious attention and that such effects were not clearly tested for by
pharmaceutical companies prior to obtaining approval for placing the drugs on the market.
Anxiolytic
An anxiolytic (also antipanic or antianxiety agent) is a drug used for the treatment of
symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety
disorders.
Beta-receptor blockers such as propranolol and oxprenolol, although not anxiolytics, can be
used to combat the somatic symptoms of anxiety.
Anxiolytics are also known as "minor tranquilizers", though their use and effects are by no
means minor; this term is less common in modern texts, and was originally derived from a
dichotomy with major tranquilizers, also known as neuroleptics or antipsychotics.
Types of anxiolytics
Benzodiazepine
Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety.
Benzodiazepines may also be indicated to cover the latent periods associated with the
medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide
variety of conditions and symptoms and are usually a first choice when short-term CNS
sedation is needed. Longer-term uses include treatment for severe anxiety. There is a risk of a
benzodiazepine withdrawal and rebound syndrome after continuous usage for longer than two
weeks. There is also the added problem of the accumulation of drug metabolites and adverse
effects. Benzodiazepines include:
 Alprazolam (Xanax)
 Chlordiazepoxide (Librium)
 Clonazepam (Klonopin)
 Diazepam (Valium)
 Lorazepam (Ativan)
Benzodiazepines exert their anxiolytic properties at moderate dosage. At higher dosage

hypnotic properties occur.

 Tofisopam (Emandaxin and Grandaxin) is a drug which is a benzodiazepine derivative.
Like other benzodiazepines, it possesses anxiolytic properties but unlike other
benzodiazepines it does not have anticonvulsant, sedative, skeletal muscle relaxant,
motor skill-impairing or amnestic properties.
SSRIs
Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a

class of compounds typically used as antidepressants in the treatment of depression, anxiety
disorders, and some personality disorders. SSRIs are primarily classified as antidepressants and
typically higher dosages are required to be effective against anxiety disorders than to be
effective against depression but nevertheless most SSRIs have anxiolytic properties.
Azapirone
Azapirones are a class of 5-HT1A receptor agonists. They lack the sedation and the dependence
associated with benzodiazepines and cause much less cognitive impairment. They may be less
effective than benzodiazepines in patients who have been previously treated with
benzodiazepines as they do not provide the sedation that these patients may expect or equate
with anxiety relief. Currently approved azapirones include buspirone (Buspar) and tandospirone
(Sediel). Gepirone (Ariza, Variza) is also in clinical development.
Barbiturates
Barbiturates exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and
addiction is high. Many experts consider these drugs obsolete for treating anxiety but valuable
for the short-term treatment of severe insomnia, though only after benzodiazepines or non-
benzodiazepines have failed. They are rarely prescribed anymore.
Hydroxyzine
Hydroxyzine (Atarax) is an old antihistamine originally approved for clinical use by the FDA in
1956. It possesses anxiolytic properties in addition to its antihistamine properties and is also
licensed for the treatment of anxiety and tension. It is also used for its sedative properties as a
premed before anesthesia or to induce sedation after anesthesia.[6] It has been shown to be as
effective as benzodiazepines in the treatment of generalized anxiety disorder while producing
fewer side effects.
Pregabalin
Pregabalin's therapeutic effect appears after 1 week of use and is similar in effectiveness to
lorazepam, alprazolam and venlafaxine but pregabalin has demonstrated superiority by
producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-
term trials have shown continued effectiveness without the development of tolerance and

additionally unlike benzodiazepines it does not disrupt sleep architecture and produces less
severe cognitive and psychomotor impairment; it also has a low potential for abuse and
dependence and may be preferred over the benzodiazepines for these reasons.
Herbal treatments
Certain herbs are reputed to have anxiolytic properties, including the following:
 Rhodiola rosea (Arctic Weed/Golden Root)

 Bacopa monnieri (Brahmi)
 Hypericum perforatum (St. John's Wort)
 Matricaria recutita (German Chamomile)
 Mitragyna speciosa (Kratom)
 Cannabis sativa (Marijuana)
 Nepeta persica (Catnip)
 Piper methysticum (Kava)
 Sceletium tortuosum (Kanna)
 Scutellaria spp. (Skullcap)
 Valeriana officinalis (Valerian)
Of these, only Kava and Brahmi have shown anxiolytic effects in randomized clinical trials, and
only Kava's effect has been independently replicated.
In mice, trials have shown anxiolytic effects at 50 mg/kg. However an increase in the dose of N.
persica exerted stimulation rather than sedation as is the case for many other herbs.
A team from Brazil found cannabidiol (a constituent of cannabis; also called CBD) to be an
effective anti-psychotic and anxiolytic. "CBD induced a clear anxiolytic effect and a pattern of
cerebral activity compatible with anxiolytic activity. Therefore, similar to the data obtained in
animal models, results from studies on healthy volunteers have strongly suggested an
anxiolytic-like effect of CBD."
Pineapple sage, or salvia elegans, is used as a treatment for anxiety in traditional Mexican
medicine, and a preliminary study on mice has yielded some support for both anxiolytic and
antidepressant properties.
Over-the-counter
Chlorpheniramine (Chlor-Trimeton) and diphenhydramine (Benadryl) have hypnotic and

sedative effects with mild anxiolytic-like properties(off-label use). These drugs are approved by
the FDA for allergies, rhinitis, and urticaria.

FLUOROQUINOLONES
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone(s)
refers to potent synthetic chemotherapeutic antibacterials,.
The first generation of the quinolones begins with the introduction of nalidixic acid in 1962 for
treatment of urinary tract infections in humans. Nalidixic acid was discovered by George Lesher
and coworkers in a distillate during an attempt at chloroquine synthesis.
They prevent bacterial DNA from unwinding and duplicating. (See Mechanism of Action later.)
Quinolones in comparison to other antibiotic classes have the highest risk of causing
colonization with MRSA and Clostridium difficile. A general avoidance of fluoroquinolones is
recommended based on the available evidence and clinical guidelines. The majority of
quinolones in clinical use belong to the subset of fluoroquinolones, which have a fluorine atom
attached to the central ring system, typically at the 6-position or C-7 position.
History
Nalidixic acid is considered to be the predecessor of all members of the quinolone family,
including the second, third and fourth generations commonly known as fluoroquinolones. This
first generation also included other quinolone drugs such as pipemidic acid, oxolinic acid, and
cinoxacin, which were introduced in the 1970s. They proved to be only marginal improvements
over nalidixic acid. Though it is generally accepted that nalidixic acid is to be considered the first
quinolone drug, this has been disputed over the years by a few researchers that believe that
chloroquine, from which nalidixic acid is derived, is to be considered the first quinolone drug,
rather than nalidixic acid.
Since the introduction of nalidixic acid in 1962, more than 10,000 analogs have been
synthesized, but only a handful have found their way into clinical practice. The fluoroquinolone
drugs are the most toxic and dangerous antibiotics in clinical practice today.
Indications
It continues to be debatable as to whether or not the effectiveness of fluoroquinolones for the
treatment of respiratory disorders is similar to that of other antibiotic classes.
Fluoroquinolone use for pneumonia is increasing, and with it so is bacterial resistance to
fluoroquinolones. The majority of the prescribing of fluoroquinolones is inappropriate, with less
than 4 percent of people prescribed quinolones being appropriate according to clinical
guidelines. Clinical guidelines in Canada recommend fluoroquinolones only for outpatient
treatment of pneumonia in a small number of patients, such as those with certain co-morbid
conditions, e.g., patients with a history of COPD, or those with recent use of antibiotics. For
severe forms of community-acquired pneumonia, the fluoroquinolones are associated with
improved treatment rates, but with no differences found in mortality between other antibiotic
classes.
Fluoroquinolones are not recommended as first-line antibiotics for acute sinusitis, as this
condition is usually self-limiting, and the risks outweigh the benefits in comparison to other
antibiotic classes.

Antibiotics including fluoroquinolones can be effective in some cases of bronchitis. However,
only about 5-10% of bronchitis cases are caused by a bacterial infection; most cases of
bronchitis are caused by a viral infection and are self-limiting and resolve themselves in a few
weeks. It has been recommended that antibiotics are limited in most cases to those whose
symptoms fail to resolve on their own.
Fluoroquinolones are often used for genitourinary infections; in general they are recommended
only after other antibiotic regimens have failed. However, for serious acute cases of
pyelonephritis or bacterial prostatitis where the patient may need to be hospitalised,
fluoroquinolones are recommended as first-line therapy. Prostatitis has been termed "the
waste basket of clinical ignorance" by prominent Stanford University urologist Dr. Thomas
Stamey. Campbell's Urology, the urologist's most authoritative reference text, identifies only
about 5% of all patients with prostatitis as having bacterial prostatitis, which can be "cured" at
least in the short term by antibiotics. In other words, 95% of men with prostatitis have little
hope for a cure with antibiotics alone, since they do not actually have any identifiable bacterial
infection.
The American Thoracic Society recommends that fluoroquinolones are not used as a first-line
agent, instead recommending macrolide or doxycycline as first-line agents. The Drug-Resistant
Streptococcus pneumoniae Working Group recommends that fluoroquinolones be used only
after other antibiotic classes have been tried and failed, or in those with demonstrated drug-
resistant Streptococcus pneumoniae. The Centers for Disease Control are concerned that
fluoroquinolones are being used as a "one-size-fits-all" treatment unnecessarily by doctors
without considering suitability and differences due to age and other risk factors. Effective
interventions have been recommended to reduce the excessive fluoroquinolone prescribing in
the United States.
Adverse effects
In general, fluoroquinolones are well tolerated, with most side-effects being mild to moderate.
On occasion, serious adverse effects occur. Some of the serious adverse effects that occur more
commonly with fluoroquinolones than with other antibiotic drug classes include CNS and
tendon toxicity. The currently marketed quinolones have safety profiles similar to that of other
antimicrobial classes. Fluoroquinolones are sometimes associated with an QTc interval
prolongation and cardiac arrhythmias, convulsions, tendon rupture, torsade de pointes and
hypoglycemia.
These adverse reactions are a class effect of all quinolones; however, certain quinolones are
more strongly associated with increased toxicity to certain organs. For example, moxifloxacin
carries a higher risk of QTc prolongation, and gatifloxacin has been most frequently linked to
disturbed blood sugar levels, although all quinolones carry these risks. Some quinolones were
withdrawn from the market because of these adverse events (for example, sparfloxacin was
associated with phototoxicity and QTc prolongation, thrombocytopenia and nephritis were
seen with tosufloxacin, and hepatotoxicity with trovafloxacin). Simultaneous use of
corticosteroids is present in almost one-third of quinolone-associated tendon rupture. The risk
of adverse events is further increased if the dosage is not properly adjusted, for example if
there is renal insufficiency.
The serious events may occur during therapeutic use at therapeutic dose levels or with acute
overdose. At therapeutic doses they include: central nervous system toxicity, cardiovascular

toxicity, tendon / articular toxicity, and, rarely, hepatic toxicity. Caution is required in patients
with liver disease. Events that may occur in acute overdose are rare, and include renal failure
and seizure. Susceptible groups of patients, such as children and the elderly, are at greater risk
of adverse reactions during therapeutic use. Adverse reactions may manifest during, as well as
after fluoroquinolone therapy has been completed.
Fluoroquinolones are considered high-risk antibiotics for the development of Clostridium
difficile and MRSA infections. A previously rare strain of C. difficile that produces a more severe
disease with increased levels of toxins is becoming epidemic, and may be connected to the use
of fluoroquinolones. Fluoroquinolones are more strongly associated with C. difficile infections
than other antibiotics, including clindamycin, third-generation cephalosporins, and beta
lactamase inhibitors. One study found that fluoroquinolones were responsible for 55% of C.
difficile infections. The European Center for Disease Prevention and Control recommends that
fluoroquinolones and the antibiotic clindamycin should be avoided in clinical practice due to
their high association with Clostridium difficile, a potentially life-threatening super-infection.
The central nervous system is an important target for fluoroquinolone-mediated neurotoxicity.
Adverse event reporting in Italy by doctors showed fluoroquinolones among the top 3
prescribed drugs for causing adverse neurological and psychiatric effects. These
neuropsychiatric effects included tremor, confusion, anxiety, insomnia, agitation, and, in severe
cases, psychosis. Moxifloxacin came out worst among the quinolones for causing CNS toxicity.
Some support and patient advocacy groups refer to these adverse events as "fluoroquinolone
toxicity". Some people from these groups claim to have suffered serious long-term harm to
their health from using fluoroquinolones. This has led to a class-action lawsuit by people
harmed by the use of fluoroquinolones as well as action by the consumer advocate group Public
Citizen. Partly as a result of the efforts of Public Citizen, the FDA ordered black box warnings on
all fluoroquinolones, advising consumers of the possible toxic effects of fluoroquinolones on
tendons.
Contraindications
Quinolones are contraindicated if a patient has epilepsy, QT prolongation, pre-existing CNS
lesions, central nervous system inflammation or those who have suffered a stroke. There are
safety concerns of fluoroquinolone use during pregnancy and, as a result, are contraindicated
except for when no other safe alternative antibiotic exists. They are also contraindicated in
children due to the risks of damage to the musculoskeletal system. Their use in children is not
absolutely contraindicated, however. For certain severe infections where other antibiotics are
not an option, their use can be justified. Quinolones should also not be given to people with a
known hypersensitivity to the drug.
Boxed warnings
U.S. Boxed Warning: Increased risk of developing tendonitis and tendon rupture in patients of
all ages taking fluoroquinolones for systemic use. This risk is further increased in individuals
over 60 years of age, taking corticosteroid drugs, and have received kidney, heart, or lung
transplants.
Musculoskeletal disorders attributed to use of quinolone antibiotics were first reported in the
medical literature in 1972, as an adverse reaction to nalidixic acid. Rheumatic disease after use
of a fluoroquinolone (norfloxacin) was first reported eleven years later. In response to a 1995
letter published in the New England Journal of Medicine, representatives of the U.S. Food and

Drug Administration (FDA) stated that the agency would "update the labeling [package insert]
for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture."
By August 1996, the FDA had not taken action, and the consumer advocacy group Public Citizen
filed a petition with the FDA, prompting the agency to act. Two months later, the FDA published
an alert in the FDA Medical Bulletin and requested that fluoroquinolone package inserts be
amended to include information on this risk.
Nine years later, in 2005, the Illinois Attorney General filed a second petition with the FDA again
seeking black box warnings and "Dear Doctor" letters emphasizing the risk of tendon rupture;
the FDA responded that it had not yet been able to reach a decision on the matter. In 2006,
Public Citizen, supported by the Illinois Attorney General, renewed its demand of ten years
prior for black box warnings by filing a third petition requesting such changes be made. When
the FDA failed to respond to these two petitions as required by law, Public Citizen, in January
2008, filed suit to compel the FDA to respond to their 2006 petition. On July 7, 2008 the FDA
requested that the makers of systemic-use fluoroquinolones add a boxed warning regarding
spontaneous tendon ruptures, and to develop a Medication Guide for patients. The package
inserts for ciprofloxacin, Avelox (moxifloxacin), Proquin XR, Factive (gemifloxacin), Floxin
(ofloxacin), Noroxin (norfloxacin) and Levaquin (levofloxacin) were amended on September 8,
2008 to include these new warnings. Bayer, which manufactures Cipro, Avelox and Proquin XR,
issued a Dear Healthcare Professional letter on October 22 concerning these changes. Ortho-
McNeil, the manufacturers of Levaquin, issued a similar letter in November. through the Health
Care Notification Network, a registration-only website that distributes drug alerts to licensed
healthcare professionals.
A review of the FDA website indicates that the majority of the generic versions of the
fluoroquinolones have not been updated to include this Boxed Warning as of September 2009.
In addition, there are numerous reports that claim that this information has not been
disseminated to the pharmacist, the name brand products continue to contain the previous
labels that are absent of this warning, and the Medication Guide has not been made available
to the pharmicist or physician for distribution.
Pharmacology
The basic pharmacophore, or active structure, of the fluoroquinolone class is based upon the
quinoline ring system. The addition of the fluorine atom at C6 is what distinguishes the
successive-generation fluoroquinolones from the first-generation quinolones. It has since been
demonstrated that the addition of the C6 fluorine atom is not a necessary requirement for the
antibacterial activity of this class (circa 1997).
Various substitutions made to the quinoline ring resulted in the development of numerous
fluoroquinolone drugs available today. Each substitution is associated with a number of specific
adverse reactions, as well as increased activity against bacterial infections, whereas the
quinoline ring, in and of itself, has been associated with severe and even fatal adverse
reactions.
Mechanism of action
Quinolones and fluoroquinolones are chemotherapeutic bactericidal drugs, eradicating bacteria
by interfering with DNA replication. The other antibiotics used today, (e.g., tetracyclines,
lincomycin, erythromycin, and chloramphenicol) do not interact with components of eukaryotic
ribosomal particles and, thus, have not been shown to be toxic to eukaryotes,[64] as opposed to
the fluoroquinolone class of drugs. Other drugs used to treat bacterial infections, such as
penicillins and cephalosporins, inhibit cell wall biosynthesis, thereby causing bacterial cell
death, as opposed to the interference with DNA replication as seen within the fluoroquinolone
class of drugs.
Quinolones inhibit the bacterial DNA gyrase or the topoisomerase II enzyme, thereby inhibiting
DNA replication and transcription. Recent evidence has shown that topoisomerase II is also a
target for a variety of quinolone-based drugs. Thus far, most of the compounds that show high
activity against the eukaryotic type II enzyme contain aromatic substituents at their C-7
positions.
Quinolones can enter cells easily via porins and, therefore, are often used to treat intracellular
pathogens such as Legionella pneumophila and Mycoplasma pneumoniae. For many Gram-
negative bacteria, DNA gyrase is the target, whereas topoisomerase IV is the target for many
Gram-positive bacteria. It is believed that eukaryotic cells do not contain DNA gyrase or
topoisomerase IV. However, there is debate concerning whether the quinolones still have such
an adverse effect on the DNA of healthy cells, in the manner described above, hence
contributing to their adverse safety profile. This class has been shown to damage mitochondrial
DNA.
Interactions
Theophylline, nonsteroidal anti-inflammatory drugs and corticosteroids enhance the toxicity of
fluoroquinolones.
Products containing multivalent cations, such as aluminum- or magnesium-containing antacids
and products containing calcium, iron, or zinc, invariably result in marked reduction of oral
absorption of fluoroquinolones.
Other drugs that interact with fluoroquinolones include antacids, Sucralfate, Probenecid,
Cimetidine, Warfarin, antiviral agents, Phenytoin, Cyclosporine, Rifampin, Pyrazinamide, and
Cycloserine.
Many fluoroquinolones, especially ciprofloxacin, inhibit the cytochrome P450 isoform CYP1A2.
This inhibition causes an increased level of, for example, antidepressants such as amitriptyline
and imipramine, clozapine (an atypical antipsychotic), caffeine, Olanzapine (an atypical
antipsychotic), Ropivacaine (a local anaesthetic), Theophylline (a xanthine), and Zolmitriptan (a
serotonin receptor agonist).
Antibiotic misuse and bacterial resistance
See also: Antibiotic misuse and Antibiotic resistance
Resistance to quinolones can evolve rapidly, even during a course of treatment. Numerous
pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now
exhibit resistance worldwide. Widespread veterinary usage of quinolones, in particular in
Europe, has been implicated.
Fluoroquinolones have been recommended to be reserved for the use in patients that are
seriously ill and may soon require immediate hospitalization. Though considered to be a very
important and necessary drugs required to treat severe and life-threatening bacterial
infections, the associated antibiotic misuse remains unchecked, which has contributed to the
problem of bacterial resistance. The overuse of antibiotics such as happens with children
suffering from otitis media has given rise to a breed of super-bacteria that are resistant to
antibiotics entirely.

For example, the use of the fluoroquinolones had increased threefold in an emergency room
environment in the United States between 1995 and 2002, while the use of safer alternatives,
such as macrolides, declined significantly. Fluoroquinolones had become the most commonly
prescribed class of antibiotics to adults in 2002. Nearly half (42%) of these prescriptions were
for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper
respiratory tract infection, according to a study that was supported in part by the Agency for
Healthcare Research and Quality. In addition, they are commonly prescribed for medical
conditions, such as acute respiratory illness, that are usually caused by viral infections.
Within a recent study concerning the proper use of this class in the emergency room, it was
revealed that 99% of these prescriptions were in error. Out of the one hundred total patients
studied, eighty-one received a fluoroquinolone for an inappropriate indication. Out of these
cases, forty-three (53%) were judged to be inappropriate because another agent was
considered first line, twenty-seven (33%) because there was no evidence of a bacterial infection
to begin with (based on the documented evaluation), and eleven (14%) because of the need for
such therapy was questionable. Out of the nineteen patients who received a fluoroquinolone
for an appropriate indication, only one patient out of one hundred received both the correct
dose and duration of therapy.
There are three known mechanisms of resistance. Some types of efflux pumps can act to
decrease intracellular quinolone concentration. In Gram-negative bacteria, plasmid-mediated
resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of
quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease
their binding affinity to quinolones, decreasing the drugs' effectiveness.
Social and economic impact
Increased hospitalizations attributed to adverse drug reactions alone account for billions of
dollars each year within the US healthcare system. Severe reactions do occur with the
fluoroquinolone class and can add significantly to the cost of care. Antibacterial adverse effects
account for nearly 25% of all adverse drug reactions among hospitalized patients.
Adverse effects of fluoroquinolones can lead to patients attending hospital emergency rooms.
Many of the important adverse effects of fluoroquinolones are widely underappreciated by
physicians, and are often misdiagnosed as other medical or psychiatric conditions. Physicians
typically fail to enquire about antibiotic use to explain with an acute presentation of new
symptoms. The important adverse effects of fluoroquinolones include hypoglycemia or
hyperglycemia, QTc prolongation, central nervous system toxicity, gastrointestinal, skin,
musculoskeletal, cardiotoxicity, and respiratory effects, phototoxicity, tendinopathy,
angioedema, and Clostridium difficile infections. A further factor that leads to misdiagnosis of
quinolone adverse effects is that some symptoms can persist or occur for the first time quite
some time after a course of quinolone has been finished, so inquiring about distant-past use of
quinolones has been recommended. Quinolones are probably the worst offending antibiotic for
causing C. difficile infections. Some of the adverse effects can present similar to acute
dementia, confusion, and psychosis. Quinolones are a common cause of cerebral dysfunction,
with neuropsychiatric disturbances being the most common quinolone adverse effects. One
study found that, of all drug classes prescribed by doctors including psychotropic drugs,
fluoroquinolones were the most common cause of neuropsychiatric adverse effects.

Patent extensions
Under the George W. Bush administration (2001–2008), patent extension legislation that
allowed Bayer AG, as well as other drug companies, a six-month patent extension for testing
their products for safety in children was signed into law. It has been estimated that Bayer AG's
revenue increased an extra $358 million due to ciprofloxacin's pediatric patent extension. The
legislation was drafted after extensive lobbying of numerous members of Congress by Bayer AG
and others. One of the four sponsors of this legislation was Chris Dodd (D-CT), who, at the time,
ranked as one of the top three beneficiaries of campaign contributions by drug companies. Sen.
Edward Kennedy (D-MA), who chaired the committee with jurisdiction over the bill, refused to
fight over the language that (if it had been included) would have reduced the drug company's
profits due to these patent extensions. The reasons for Sen. Edward Kennedy's decision not to
fight for the inclusion of this language were not made known.
The results of these pediatric trials indicated that arthropathy occurred more frequently in
patients that received ciprofloxacin (within these studies). The affected joints included the
knees, elbows, ankles, hips, wrists, and shoulders of the pediatric patients. In one study, at six
weeks arthropathy was seen in 9.3% of ciprofloxacin patients. These rates increased
significantly after one year to 13.7% of the ciprofloxacin patients. Such arthropathy occurred
more frequently in patients treated with ciprofloxacin than any other control drug, regardless
of whether they received IV ciprofloxacin or the oral version of the drug. Ciprofloxacin patients
reported more than one event and on more than one occasion when compared to the control
patients. The overall incidence of adverse events at six weeks was 41% in those patients being
treated with ciprofloxacin. Serious adverse events were seen in 7.5% of these patients and 3%
of the patients discontinued the drug due to adverse events. Despite these results the FDA
stated that “The data support updating the package insert to include safety; and treatment
recommendations for pediatric patients between 1 and 17 years of age with complicated
urinary tract infection or pyelonephritis.”
Within a 2005 memo, the FDA reviewed seventeen unique pediatric cases reported to the FDA
during the thirteen-month period after the pediatric exclusivity for ciprofloxacin had been
granted. During this period, there was one report of death, two of disability, and four of
hospitalization. The disabilities involved the inability to walk (in a 12-year-old female patient)
and the inability to run (in a 12-year-old male patient). The hospital admissions were for
pseudomembranous colitis, pancytopenia, tendonitis, and Stevens Johnson syndrome. The
female patient received 5 weeks of ciprofloxacin oral therapy at the recommended doses. Even
though ciprofloxacin was discontinued, she could not stand or ambulate and required a
wheelchair one month later. These seventeen unique pediatric cases showed mostly
hematological, musculoskeletal, allergic/hypersensitivity, and central nervous system adverse
events. It does not appear that this executive summary was ever released to the medical
community.
 Economic impact: adverse reactions:
The adverse drug reaction profile of ciprofloxacin and other fluoroquinolone drugs has
spawned a grass-roots movement of those so affected to lobby for Black Box Warnings and
Dear Doctor Letters as well as the petitioning of the FDA for the removal of some
fluoroquinolone drugs from clinical practice

Current litigation
The effectiveness and the proven clinical need for the drugs found within this class have rarely
been called into question. They have a proven track record with regard to eradicating bacterial
infections and are to be considered an essential tool within the medical community. However,
there is controversy concerning the safety profile of quinolones, as well as their proper use.
At present, there is a significant number of cases pending before the United States District
Court, District of Minnesota, involving the drug Levaquin. On June 13, 2008 a Judicial Panel On
Multidistrict Litigation (MDL) granted the Plaintiffs’ motion to centralize individual and class-
action lawsuits involving Levaquin in the District of Minnesota over objection of Defendants,
Johnson and Johnson / Ortho McNeil.
Most recently, on July 6, 2009, the New Jersey Supreme Court had also designated litigation
over Levaquin as a mass tort and has assigned it to an Atlantic County, N.J., judge. The suits
charge that the drug has caused Achilles tendon ruptures and other permanent damage.
Several class action lawsuits had been filed in regards to the adverse reactions suffered by
those exposed to ciprofloxacin during the anthrax scare of 2001, as well.
Generations
Researchers divide the quinolones into generations based on their antibacterial spectrum. The
earlier-generation agents are, in general, more narrow-spectrum than the later ones, but there
is no standard employed to determine which drug belongs to which generation. The only
universal standard applied is the grouping of the non-fluorinated drugs found within this class
(quinolones) within the first-generation heading. As such, there exists a wide variation within
the literature dependent upon the methods employed by the authors.
 Some researchers group these drugs by patent dates
 Some by a specific decade (i.e., '60s, '70s, '80s, etc.)
 Others by the various structural changes

The first generation is rarely used today. Nalidixic acid was added to the OEHHA Prop 65 list as a
carcinogen on May 15, 1998. A number of the second-, third-, and fourth-generation drugs
have been removed from clinical practice due to severe toxicity issues or discontinued by their
manufacturers. The drugs most frequently prescribed today consist of Avelox (moxifloxacin),
Cipro (ciprofloxacin), Levaquin (levofloxacin), and, to some extent, their generic equivalents.

Fluoroquinolones:- O
O
O O F
COOH
COOH F
COOH COOH
O
H3C O X N N
N N
N N N
H3C N O
H5 C2 *0 CH3
H5C2 HN R
Nalidixic acid Oxolinic Acid X = CH Norfloxacin R = C2H5 Ofloxacin
Cinoxacin, X = N Ciproploxacin R = Cyclo-Pr Levofloxacin

O
O O
F COOH NH2 O
F COOH F COOH F
COOH
N N
N N H N N H C
HN F N 3 N N
H5C2
OCH3 OCH3 H
HN F
HN
H3C
CH3
CH3
Lomefloxacin Gatifloxacin Moxifloxacin Sparfloxacin
First-generation
 cinoxacin (Cinobac) (Removed from clinical use)
 flumequine (Flubactin) (Genotoxic carcinogen)(Veterinary use)
 nalidixic acid (NegGam, Wintomylon) (Genotoxic carcinogen)
 oxolinic acid (Uroxin) (Currently unavailable in the United States)
 piromidic acid (Panacid) (Currently unavailable in the United States)
 pipemidic acid (Dolcol) (Currently unavailable in the United States)
 rosoxacin (Eradacil) (Restricted use, currently unavailable in the United States)
Second-generation
The second-generation class is sometimes subdivided into "Class 1" and "Class 2".
 ciprofloxacin (Zoxan, Ciprobay, Cipro, Ciproxin)
 enoxacin (Enroxil, Penetrex) (Removed from clinical use)
 fleroxacin (Megalone, Roquinol) (Removed from clinical use)
 lomefloxacin (Maxaquin) (Discontinued in the United States)
 nadifloxacin (Acuatim, Nadoxin, Nadixa) (Currently unavailable in the United States)
 norfloxacin (Lexinor, Noroxin, Quinabic, Janacin) (restricted use)
 ofloxacin (Floxin, Oxaldin, Tarivid) (Only as ophthalmic in the United States)
 pefloxacin (Peflacine) (Currently unavailable in the United States)
 rufloxacin (Uroflox) (Currently unavailable in the United States)
Third-generation
Unlike the first- and second-generations, the third-generation is active against streptococci.
 balofloxacin (Baloxin) (Currently unavailable in the United States)
 grepafloxacin (Raxar) (Removed from clinical use)
 levofloxacin (Cravit, Levaquin)
 pazufloxacin (Pasil, Pazucross) (Currently unavailable in the United States)
 sparfloxacin (Zagam) (Currently unavailable in the United States),
 temafloxacin (Omniflox) (Removed from clinical use)

 tosufloxacin (Ozex, Tosacin) (Currently unavailable in the United States)
 Fourth-generation
Fourth generation fluoroquinolones act at DNA gyrase and topoisomerase IV. This dual action
slows development of resistance.
 clinafloxacin (Currently unavailable in the United States)
 gatifloxacin (Zigat, Tequin) (Zymar -opth.) (Tequin removed from clinical use)
 gemifloxacin (Factive)(Currently unavailable in the United States)
 moxifloxacin (Avelox,Vigamox (restricted use).
 sitafloxacin (Gracevit) (Currently unavailable in the United States)
 trovafloxacin (Trovan) (Removed from clinical use)
 prulifloxacin (Quisnon) (Currently unavailable in the United States)
In development
 garenoxacin (Geninax)(Application withdrawn due to toxicity issues)
 delafloxacin
Urinary Antiseptics:- Nitrofurantion and furazolidone are also used as urinary antiseptic that
inhibit DNA gyrase. Specially effective in E. coli infection. Nitrofurantoin is given in micro
particle form to increase the absorption of the drug from intestine (Microdantin).
Nitrofuranton Furazolidone
O
O
O 2N NH
NH N O
O O 2N NH N
O
O 3-{[(5-nitrofuran-2-yl)methyl]amino}-1,3-oxazolidin-2-one
1-{[(5-nitrofuran-2-yl)methyl]amino}imidazolidine-2,4-dione
Furazolidone is red color dye that causes discoloration (Pink color) of urine.

GENERAL ANESTHETICS
General anesthetic are the agents that cause reversible loss of consciousness. These are useful
in surgical anesthesia for surgery. There are two types, inhalational and intravenous. When
diethyl ether is used as surgical anesthetic; this is characterized by Guedel’s sign of anesthesia
and divided in four stages 1) analgesia 2) delirium 3) surgical anesthesia 4) respiratory
depression.
Stages of anaesthesia
The four stages of anaesthesia were described in 1937. Despite newer anaesthetic agents and
delivery techniques, which have led to more rapid onset and recovery from anaesthesia, with
greater safety margins, the principles remain.
 Stage 1: Stage 1 anaesthesia, also known as the "induction", is the period between the
initial administration of the induction agents and loss of consciousness. During this
stage, the patient progresses from analgesia without amnesia to analgesia with
amnesia. Patients can carry on a conversation at this time.
 Stage 2: Stage 2 anaesthesia, also known as the "excitement stage", is the period
following loss of consciousness and marked by excited and delirious activity. During this
stage, respirations and heart rate may become irregular. In addition, there may be
uncontrolled movements, vomiting, breath holding, and pupillary dilation. Since the
combination of spastic movements, vomiting, and irregular respirations may lead to
airway compromise, rapidly acting drugs are used to minimize time in this stage and
reach stage 3 as fast as possible.
 Stage 3: Stage 3, "surgical anaesthesia". During this stage, the skeletal muscles relax,
and the patient's breathing becomes regular. Eye movements slow, then stop, and
surgery can begin. It has been divided into 4 planes:
1. eyes initially rolling, then becoming fixed

2. loss of corneal and laryngeal reflexes
3. pupils dilate and loss of light reflex
4. intercostal paralysis, shallow abdominal respiration, dilated pupils
 Stage 4: Stage 4 anaesthesia, also known as "overdose", is the stage where too much
medication has been given relative to the amount of surgical stimulation and the patient
has severe brain stem or medullary depression. This results in a cessation of respiration
and potential cardiovascular collapse. This stage is lethal without cardiovascular and
respiratory support. This can be fatal.
Other agents are chloroform, halothane, nitrous oxide, enflurane, desflurane, sevoflurane and
methoxyflurane. These are easily converted in gaseous form and are used to maintain

anesthesia. The agents that are given in intravenous form are thiopental, propafol, ketamine,
midazolam and etodimate.
Inhalational anesthetics
F F F F F
Cl Cl F
H C C F H C C O C H F C C O C H
Br F F F F F F
F
Halothane Enflurane Desflurane

F F F
C F F H
F Cl
F C C O C H H C C O C H
F H H Cl F H
Sevoflurane Methoxyflurane
Intravenous anesthetics
O CH3 CH3 H O
OH N
NH CH3 CH3
H3C CH3 S
CH CH2 CH2 CH3
N
H O CH3
Cl
Ketamine Propofol Thiopantal

HISTAMINE ANTAGONIST
A histamine antagonist is an agent that inhibits action of histamine via histamine receptors. H1
antihistamines are used as treatment for symptoms of allergies such as runny nose. Allergies
are caused by an excessive type 1 hypersensitivity response of the body to allergens, such as
pollen released by plants. An allergic reaction, which if severe enough can lead to anaphylaxis,
results in excessive release of histamines and other mediators by the body. Other uses of H 1
antihistamines help with symptoms of local inflammation that results from various conditions,
such as insect stings, even if there is no allergic reaction. Other commonly used examples of
antihistamines include the H2 antagonists (Cimetidine) which are widely used for the treatment
of acid reflux and stomach ulcers as they decrease gastric acid production.
Clinical effects
Histamines will produce increased vascular permeability causing fluid to escape from capillaries
into the tissues, which leads to the classic symptoms of an allergic reaction – a runny nose and
watery eyes.
Antihistamines suppress the histamine-induced wheal (swelling) and flare (vasodilation)

response by blocking the binding of histamine to its receptors on nerves, vascular smooth
muscle, glandular cells, endothelium, and mast cells. They effectively exert competitive
antagonism of histamine for H1-receptors. Itching and sneezing are suppressed by
antihistamine blockade of H1-receptors on nasal sensory nerves. Antihistamines are commonly
used for relief of allergies caused by intolerances of proteins.
Clinical: H1- and H2-receptor antagonists
H1-receptor antagonists
In common use, the term antihistamine refers only to H1 antagonists, also known as H1
antihistamines. It has been discovered that these H1-antihistamines are actually inverse
agonists at the histamine H1-receptor, rather than antagonists per se. Clinically, H1 antagonists
are used to treat allergic reactions. Sedation is a common side effect, and some H1 antagonists,
such as diphenhydramine and doxylamine, are also used to treat insomnia. However, second
generation antihistamines do not cross the blood brain barrier, and as such do not cause
drowsiness

Classification
1. Ethylene diamine derivatives

Mepyramine (Pyrilamine), Tripelennamine
2. Amino Alkyl Ethers
Diphenhydramine (Benadryl), Clemastine, Doxylamine , Medrylamine, Dimenhydrinate
3. Cyclic basic chain analogoues
Hydroxazine, cyclizine, chlorcyclizine, buclizine, cinnarzine, Meclizine (most commonly
used as an antiemetic)
4. Mono amino propyl analogos
Pheniramine, Chlorpheniramine, dexchlorpheniramine
5. Tricyclic antihistaminic
Promethazine, cyproheptadiene, azatadine, ketotiphene, dimethindene
6. Newer antihistaminic with fewer sedation (second generation)
Loratadine, Desloratadine, Fexofenadine, Cetirizine, Ebastine, Levocetirizine,
Olopatadine (used locally), Quetiapine (antipsychotic), embramine
 Vitamin C (also known as ascorbic acid)

Ethylene diamine derivatives Amino alkyl ether derivatives
R R
CH3
CH3 O
N N
N CH3
CH3
N
R = OCH3 Mepyramine R = CH3 Doxylamine

R=H Tripelennamine R=H Diphenhydramine
Cyclic Basic Chain derivatives Monopropylamino derivatives
R1 R1 CH3
R N
N N CH3
N
R1 = H , R = CH3, Cyclizine R = H , Pheniramine

R = Cl Chorpheniramine
R1= Cl, R = CH3, Chorcyclizine
TriCyclic derivatives Newer Drugs

Cl OH
S
N
N CH3 HO N
N CH3
H2C N
CH3 R = CH3 Terfenadine H3C
CH3 H R
Promethazine Desloratadine R = COOH Fexofenadine
H2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists. H2
histamine receptors are found principally in the parietal cells of the gastric mucosa. H2
antagonists are used to reduce the secretion of gastric acid, treating gastrointestinal conditions
including peptic ulcers and gastroesophageal reflux disease.
 Cimetidine
 Famotidine
 Ranitidine
 Nizatidine
 Roxatidine
 Lafutidine

H2 - Antagonist
Cimetidine NH NH Ranitidine NH NH
H3C S CH3 H3C O CH3
N S
HN N N CN H3C NO 2
2-cyano-1-methyl-3-(2-{[(5-methyl-1H-imidazol-4-yl) (E)-N-{2-[({5-[(dimethylamino)methyl]furan-2-yl}methyl)
methyl]sulfanyl}ethyl)guanidine sulfanyl]ethyl}-N'-methyl-2-nitroethene-1,1-diamine
NH NH NH NH2
H3C N CH3 H2N N N
N S S
H3C NO 2 H2N N SO2NH 2
S S
Nizatidine Famotidine
Proton Pump Inhibitors (PPI)
Proton pump inhibitors are used as ulcer healing substances like omeprazole, esomeprazole,
lansoperazole, pantoperazole and rabeprazole.
Proton Pump Inhibitors:- R R1 R2 R3

R1
R2 1. Omeprazole OCH3 OCH3 CH3 CH3
4 O
R 5 N R3
3 S
2. Pantoprazole OCHF2 OCH3 OCH3
2
6 N N
7 H
3. Lansoprazole H OCH2CF3 CH3
1
4. Rabeprazole H OCH2CH2CH2OCH3 CH3
Experimental: H3- and H4-receptor antagonists
These are experimental agents and do not yet have a defined clinical use, although a number of
drugs are currently in human trials. H3-antagonists have a stimulant and nootropic effect, and
are being investigated for the treatment of conditions such as ADHD, Alzheimer's Disease, and
schizophrenia, whereas H4-antagonists appear to have an immunomodulatory role and are
being investigated as anti-inflammatory and analgesic drugs.
 Ciproxifan
 Clobenpropit
 Thioperamide

 Thioperamide
Mast cell stabilizers
Mast cell stabilizers appear to stabilize the mast cells to prevent degranulation and mediator
release. These drugs are not usually classified as histamine antagonists, but have similar
indications.
 Cromoglicate (cromolyn)
 Nedocromil
 β2 adrenergic agonists
Serotonin receptor agonist
A serotonin receptor agonist is a compound that activates serotonin receptors, mimicking the
effect of the neurotransmitter serotonin. There are various serotonin receptors and ligands.
5-HT1A receptor
Azapirones such as buspirone, gepirone, and tandospirone are 5-HT1A agonists marketed
primarily as anxiolytics, but also recently as antidepressants.
5-HT1B receptor
Triptans such as sumatriptan, rizatriptan, and naratriptan, are 5-HT1B receptor agonists that are
used to abort migraine and cluster headache attacks.
5-HT1D receptor
In addition to being 5-HT1B agonists, triptans are also agonists at the 5-HT1D receptor, which
contributes to their anti-migraine effect.
5-HT1F receptor
LY-334,370 was a selective 5-HT1F agonist that was being developed by Eli Lilly and Company for
the treatment of migraine and cluster headaches. Development was halted however due to
toxicity detected in animal test subjects. Lasmiditan has successfully completed Phase II clinical
trials in early 2010.
5-HT2A receptor
Psychedelic drugs such as LSD, mescaline, psilocin, DMT, and 2C-B act as 5-HT2A agonists. Their
action at this receptor is responsible for their hallucinogenic effects.

It is now known that many of these drugs inhibit many other 5HT receptors in addition to the 5-
HT2A.
5-HT2C receptor
Lorcaserin is a thermogenic and anorectic weight-loss drug which acts as a selective 5-HT2C
agonist.
5-HT4 receptor
Cisapride is a 5-HT4 receptor agonist that has been used to treat disorders of gastrointestinal
motility.

LOCAL ANESTHETICS
Local anesthetic reversibly blocks impulse conduction in peripheral nervous system; there by
producing transient loss of sensation in circumscribed area of the body, without causing general
loss of consciousness. These are given either topically or parentrally to a localized area.
Mechanism of action: Local anesthetics block voltage sensitive sodium channel that causes
depolarization. The channel is composed of glycoprotein and has selective filters (pores for
sodium ions). These pores have twelve times more speed than other cation like K+. When
depolarization occurs these selective filters open and local anesthetic blocks this voltage
sensitive sodium channel. There are other two chemicals tetrodoxin and saxitoxin that block
the voltage sensitive sodium channel in the same manner.
Local anesthetics are tertiary amines that contain pH between7.5 – 9 so these form water
soluble salts [BH+] and bind to the receptor. The drug(B) can bind directly to the receptor also.
According to Henderson Hesselbalch equation
pH = pKa – log10 [B]/[BH+]
Discovery: The initial lead derived from the leaves of Erythroxylon coca plant. Native of peru
country used to chew the leaves for general feeling of well being and to prevent hunger. Saliva
after chewing the leaves was used to relieve the painful wounds. Niemann isolated crystalline
form of cocaine from the leaves of coca in1860. Von Anrep recommended as clinical agent for
after experiments on animals. Koller (1884) used first time in surgery of teeth.
O OH
COOMe COOH
O
Hydrolysis + H3C OH
H3C N O H3C N OH +
Cocaine Ecgonine Benzoic acid Methanol
The major drawback of this drug is adducting property. This was disappeared when
carboxymethyl group was removed. The cocaine is ester of benzoic acid with ecgonine and
methyl alcohol. Ecgonine contain bicyclic tropane ring which is not essential for local anesthetic
activity so bezoyl tropane and procaine was the new drugs to improve the side effects of
cocaine.

Benzoyl tropine Procaine
O H2N O C2 H5
N
H3C N O O C2 H 5
2-(diethylamino)ethyl 4-aminobenzoate
8-methyl-8-azabicyclo[3.2.1]oct-3-yl benzoate
These above drugs (Benzoyltropine and Procaine) are free from addicting properties but due to
short duration of action and less intrinsic activity; epinephrine was administered with these
drugs. Other side effects of these drugs are 1) allergic reactions 2) tissue irritability and 3) poor
stability in aqueous medium. To improve these properties, Euler discover other natural plant
origin drug Isogramine. Further new synthetic bioisoster of this drug was Lidocaine (Xylocaine
or Lignocaine). The drug lidocaine is free from these side effects and most widely used drug.
m-Xylidine 2-chloro-N-(2,6-dimethylphenyl)acetamide
CH3 CH3 CH3
C2H5 Xylocaine C H
CH 2Cl 2 5
Cl
NH2 + NH CH 2+Cl H N NH
N
C2H5
O
CH3 chloroacetyl chloride O CH3 O C2H5
CH3
2,6-dimethylaniline
2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide
Benzocaine is lipophilic drug that is used as local anesthetic. Tetracaine is most widely used
drug in amino ester group drugs.
SAR (structure activity relationship):- There are three portion of the drug lipophilic – Aliphatic
chain - hydrophilic in which hydrophilic group is tertiary amino, the carbon chain is from one to
three carbon and lipophilic group is PABA, benzoic acid of dimethyl aniline. If ortho and para
position is replaced by electron releasing groups then they increase the potency by resonance
and positive inductive effect. The zwitterions is most suitable for binding to the receptor like
procaine and lidocaine.

Lipophilic Chain Hydrophilic
H2N O C2H5
Procaine N
O C2H5
CH3
C2H5
NH
Lidocaine N
CH3 O C2H5
O C2H5
N
Propivane O C2H5
C3H7
Acetylcholine H3C O + CH3

N CH3
CH3
O
Metabolism:- Esters are hydrolyzed by enzyme esterase in the liver and inactivated. Amides are
some stable to hydrolysis. The drug compete with sulpha drugs so increase in duration of action
when administered with PABA antagonists.

MACROLIDE
The macrolides are a group of drugs (typically antibiotics) whose activity stems from the
presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy
sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-,
15-, or 16-membered. Macrolides belong to the polyketide class of natural products.
(H 3C) 2N
CH3
CH3
8
R HO O Erythromycin R = O and R1 = H
7
9
H3C
CH3 Desosamine Clarithromycin R = O and R1 = CH3
6
10 O
1
11 R O Roxithromycin R = NOCH2OCH2CH2OCH3
5 CH3
OH H3CO and R1 = H
OH
12 4
CH3
H3C 13 3
H5C2 O CH3
2 O
O
14 CH3 Cladinose
1
O
Clarithromycin: It is 6-methyl ether of erythromycin. This group inhibits peroxide formation

with 12-OH group in the macrolacton ring.
Roxithromycin: It is produced by reaction of substituted hydroxyl amine at C-9 of macrolide
ketone to produce oxime that also inhibit formation of ketal .
Azithromycin: It is prepared by Beckmann rearrangement inserting N-CH3 between 9 and 10-

position of macrolide ring. It has 15 membered macrolactone ring
Antibiotic macrolides
US FDA approved : Not US FDA approved:
 Azithromycin (does not inhibit CYP3A4) Carbomycin A

 Clarithromycin Josamycin
 Dirithromycin Kitasamycin
 Erythromycin Midecamycin/midecamycin acetate
 Roxithromycin Oleandomycin
 Telithromycin Spiramycin - approved in Europe and other
countries
Troleandomycin - used in Italy and
Turkey

Tylosin/tylocine - used in animals
Non-antibiotic macrolides
The drugs tacrolimus, pimecrolimus and sirolimus which are used as immunosuppressants or
immunomodulators are also macrolides. They have similar activity to ciclosporin.
Ketolides
Ketolides are a new class of antibiotics that are structurally related to the macrolides. They are
used to fight respiratory tract infections caused by macrolide-resistant bacteria. Ketolides are
especially resistant, as they have a double-binding site. Cladinose sugar of erythromycin is
replaced with keto group in telithromycin
Macrolides include:
 Telithromycin, Cethromycin, Spiramycin - used for treating toxoplasmosis, Ansamycin,

Oleandomycin, Carbomycin, Tylocine
Uses
Antibiotic macrolides are used to treat infections caused by Gram positive bacteria,
Streptococcus pneumoniae, and Haemophilus influenzae infections such as respiratory tract and
soft tissue infections. The antimicrobial spectrum of macrolides is slightly wider than that of
penicillin, and, therefore, macrolides are a common substitute for patients with a penicillin
allergy. Beta-hemolytic streptococci, pneumococci, staphylococci, and enterococci are usually
susceptible to macrolides. Unlike penicillin, macrolides have been shown to be effective against
mycoplasma, mycobacteria, some rickettsia, and chlamydia.
Macrolides are not to be used on non-ruminant herbivores, such as horses and rabbits. They
rapidly produce a reaction causing fatal digestive disturbance. It can be used in horses less than
one year old, but care must be taken that other horses (such as a foal's mother) do not come in
contact with the macrolide treatment.
Mechanism of action
Antibacterial
Macrolides are protein synthesis inhibitors. The mechanism of action of macrolides is inhibition
of bacterial protein biosynthesis, and they are thought to do this by preventing
peptidyltransferase from adding the peptidyl attached to tRNA to the next amino acid (similarly
to chloramphenicol) as well as inhibiting ribosomal translocation. Another potential mechanism
is premature dissociation of the peptidyl-tRNA from the ribosome.
Macrolide antibiotics do so by binding reversibly to the P site on the subunit 50S of the
bacterial ribosome. This action is mainly bacteriostatic, but can also be bactericidal in high

concentrations. Macrolides tend to accumulate within leukocytes, and are, therefore,
transported into the site of infection.
Immunomodulation
Diffuse panbronchiolitis
The macrolide antibiotics erythromycin, clarithromycin, and roxithromycin have proven to be

an effective long-term treatment for the idiopathic, Asian-prevalent lung disease diffuse
panbronchiolitis (DPB). The successful results of macrolides in DPB stems from controlling
symptoms through immunomodulation (adjusting the immune response), with the added
benefit of low-dose requirements.
With macrolide therapy in DPB, great reduction in bronchiolar inflammation and damage is
achieved through suppression of not only neutrophil granulocyte proliferation, but also
lymphocyte activity and obstructive secretions in airways. The antimicrobial and antibiotic
effects of macrolides, however, are not believed to be involved in their beneficial effects
toward treating DPB. This is evident, as the treatment dosage is much too low to fight infection,
and in DPB cases with the occurrence of the macrolide-resistant bacterium Pseudomonas
aeruginosa, macrolide therapy still produces substantial anti-inflammatory results.
Resistance
The primary means of bacterial resistance to macrolides occurs by post-transcriptional

methylation of the 23S bacterial ribosomal RNA. This acquired resistance can be either plasmid-
mediated or chromosomal, i.e., through mutation, and results in cross-resistance to macrolides,
lincosamides, and streptogramins (an MLS-resistant phenotype).
Two other types of acquired resistance rarely seen include the production of drug-inactivating
enzymes (esterases or kinases), as well as the production of active ATP-dependent efflux
proteins that transport the drug outside of the cell.
Azithromycin has been used to treat strep throat (Group A streptococcal (GAS) infection caused
by Streptococcus pyogenes) in penicillin-sensitive patients, however macrolide-resistant strains
of GAS are not uncommon. Cephalosporin is another option for these patients.
Side-effects
A 2008 British Medical Journal article highlights that the combination of macrolides and statins
(used for lowering cholesterol) is not advisable and can lead to debilitating myopathy. This is
because macrolides are potent inhibitors of the cytochrome P450 system, particularly of
CYP3A4. Macrolides, mainly erythromycin and clarithromycin, also have a class effect of QT
prolongation, which can lead to torsade de pointes. Macrolides exhibit enterohepatic recycling;
that is, the drug is absorbed in the gut and sent to the liver, only to be excreted into the
duodenum in bile from the liver. This can lead to a build-up of the product in the system,
thereby causing nausea.

Antibacterial that bind on 30 S ribosome in protein biosynthesis:-
Aminoglycosides (initiation inhibitors)
-mycin (Streptomyces):- Streptomycin, Neomycin (Framycetin, Paromomycin, Ribostamycin),
Kanamycin (Amikacin, Arbekacin, Bekanamycin, Dibekacin, Tobramycin)
Spectinomycin· Hygromycin B
Paromomycin
-micin (Micromonospora):- Gentamicin (Netilmicin, Sisomicin, Isepamicin)
Verdamicin
Astromicin
Tetracycline antibiotics(tRNA binding):- Doxycycline# •Chlortetracycline • Clomocycline •

Demeclocycline • Lymecycline • Meclocycline • Metacycline • Minocycline • Oxytetracycline •
Penimepicycline • Rolitetracycline • Tetracycline
Glycylcyclines:-Tigecycline
Antibacterial that bind on 50 S ribosome in protein biosynthesis
Oxazolidinone (initiation inhibitors:-) Linezolid • Torezolid · Eperezolid · Posizolid · Radezolid

Peptidyl transferase inhibitors:-
Amphenicols:- Chloramphenicol · Azidamfenicol · Thiamphenicol · Florfenicol
Pleuromutilins:- Retapamulin · Tiamulin · Valnemulin
MLS (transpeptidation/translocation inhibitors)
Macrolides:- Erythromycin · Azithromycin · Spiramycin · Midecamycin ·
Oleandomycin ·Roxithromycin · Josamycin · Troleandomycin · Clarithromycin · Miocamycin ·
Rokitamycin · Dirithromycin · Flurithromycin · Ketolide (Telithromycin, Cethromycin)
Lincosamides:- Clindamycin · Lincomycin
Streptogramins:- Pristinamycin · Quinupristin/dalfopristin · Virginiamycin
Lincomycin:-
Lincomycin is a lincosamide antibiotic that comes from the actinomyces Streptomyces
lincolnensis. It has been structurally modified by thionyl chloride to its more commonly known
7-chloro-7-deoxy derivative, clindamycin.

C3H7
C3H7
CH3
CH3
HO C H
H C Cl
N
H C NH SN2 reaction N
H C NH
5 O CH3
O 5 O CH3
O
4 1 Alkyl Halide 4 1
OH
HO S CH3 OH
3
2 HO 2
S CH3
OH 3
OH
Lincomycin Clindamycin
Although similar in structure, antibacterial spectrum, and in mechanism of action to macrolides,

they are also effective against other species as well, i.e., actinomycetes, mycoplasma, and some
species of Plasmodium.
However, because of its adverse effects and toxicity, it is rarely used today and reserved for
patients allergic to penicillin or where bacteria has developed resistance.Clinical pharmacology
Intramuscular administration of a single dose of 600 mg of Lincomycin produces average peak
serum levels of 11.6 micrograms/ml at 60 minutes, and maintains therapeutic levels for 17 to
20 hours, for most susceptible gram-positive organisms. Urinary excretion after this dose
ranges from 1.8 to 24.8 percent (mean: 17.3 percent).
A two-hour intravenous infusion of 600 mg of Lincomycin achieves average peak serum levels
of 15.9 micrograms/ml and yields therapeutic levels for 14 hours for most susceptible gram-
positive organisms. Urinary excretion ranges from 4.9 to 30.3 percent (mean: 13.8 percent).
The biological half-life after IM or IV administration is 5.4 ± 1.0 hours. The serum half-life of
lincomycin may be prolonged in patients with severe impairment of renal function, compared
to patients with normal renal function. In patients with abnormal hepatic function, serum half-
life may be twofold longer than in patients with normal hepatic function. Hemodialysis and
peritoneal dialysis are not effective in removing lincomycin from the serum.
Tissue level studies indicate that bile is an important route of excretion. Significant levels have
been demonstrated in the majority of body tissues. Although lincomycin appears to diffuse in
the cerebrospinal fluid (CSF), levels of lincomycin in the CSF appear inadequate for the
treatment of meningitis.
Dosage and administration
Adults
Serious infections - 600 mg (2 ml) IM every 24 hours. More severe infections - 600mg (2 ml)
every 12 hours. The IV dose will be determined by the seriousness of the infection. For serious
infections, doses of 600 mg to 1000 mg are given every 8 to 12 hours. For more severe
infections, these doses may have to be increased. In life-threatening situations, daily IV
administration of as much as 8000 mg have been given.
Pediatric Patients
Pediatric patients over one month of age: Serious infections—one IM injection of 10mg/kg
every 24 hours. More severe infections—one IM injection of 10 mg/kg every 12 hours, or more

often as indicated by susceptibility testing, renal and hepatic functioning. IV dosing is 10 to 20
mg/kg/day in divided doses every 8 to 12 hours.
Subconjunctival injections
An injection of 0.75 mg, given subconjuctivally, will result in ocular fluid levels of antibiotic
(lasting for at least 5 hours) with Minimum Inhibitory Concentrations sufficient for most
susceptible pathogens.
Patients with diminished renal function
When therapy with lincomycin is required in individuals with severe impairment of renal
function, an appropriate dose is 25 to 30 percent of that recommended for patients with
normally functioning kidneys.
Side effect:- Pseudo membrane colitis is major side effect. It can be treated by vancomycin
antibiotics.

PENICILLIN
Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium
fungi.[1] Penicillin antibiotics are historically significant because they are the first drugs that
were effective against many previously serious diseases such as syphilis and Staphylococcus
infections. Penicillins are still widely used today, though many types of bacteria are now
resistant. All penicillins are Beta-lactam antibiotics and are used in the treatment of bacterial
infections caused by susceptible, usually Gram-positive, organisms.
The term "penicillin" can also refer to the mixture of substances that are naturally, and
organically, produced.

Structure
The term "penam" is used to describe the core skeleton of a member of a penicillin antibiotic.
This skeleton has the molecular formula R-C9H11N2O4S, where R is a variable side chain.
Normal penicillin has a molecular weight of 313 to 334 g/mol (latter for penicillin G). Penicillin
types with additional molecular groups attached may have a molar mass around 500 g/mol. For
example, cloxacillin has a molar mass of 476 g/mol and dicloxacillin has a molar mass of 492
g/mol
Biosynthesis
Penicillin biosynthesis.
Overall, there is a total of three main and important steps to the biosynthesis of penicillin G
(benzylpenicillin)
 The first step in the biosynthesis of penicillin G is the condensation of three amino acids
L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide. Before condensing into a
tripeptide, the amino acid L-valine will undergo epimerization and become D-valine.
After the condensation, the tripeptide is named δ-(L-α-aminoadipyl)-L-cysteine-D-valine,

which is also known as ACV. While this reaction occurs, we must add in a required
catalytic enzyme ACVS, which is also known as δ-(L-α-aminoadipyl)-L-cysteine-D-valine
synthetase. This catalytic enzyme ACVs is required for the activation of the three amino
acids before condensation and the epimerization of transforming L-valine to D-valine.
 The second step in the biosynthesis of penicillin G is to use an enzyme to change ACV
into isopenicillin N. The enzyme is isopenicillin N synthase with the gene pcbC enclosed.
The tripeptide on the ACV will then undergo oxidation, which then allows a ring closure
so that a bicyclic ring is formed.[7][8] Isopenicillin N is a very weak intermediate because it
does not show much antibiotic activity.[10]
 The last step in the biosynthesis of penicillin G is the exchange of the side-chain group
so that isopenicillin N will become penicillin G. Through the catalytic coenzyme
isopenicillin N acyltransferase (IAT), the alpha-aminoadipyl side-chain of isopenicillin N is
removed and exchanged for a phenylacetyl side-chain. This reaction is encoded by the
gene penDE, which is unique in the process of obtaining penicillins.
Penicillins:-
O Benzylpenicillin - Phenoxymethylpenicillin
CH 2 O CH2-
H
6 S
R NH CH3
5 4 R= R=
3
N CH3 Penicillin G Penicillin V
7 1 2
O
COOH
Penicillinase resistant Parenteral Penicillin Oral Penicillins

OCH3 X N O
Oxacillin X=Z=H
-
Cloxacillin X = Cl Z = H CH3
R= Methicillin
OCH3 Dicloxacillin X = Z = Cl -
Z
Penicillinase sensitive (Broad-Spectrum) Parenteral Penicillin Oral Penicillins
O O X
COOH COOH
- X = H Ampicillin
-
R= R= R=
- X = OH Amoxicillin
S
-
Carbenicillin Carindacillin Ticarcillin H2N
O O
Beta-Lactamase Inhibitors:- H CH 2OH
H
S
O CH3
Clavulanic acid Sulbactum
N N CH3
O
O
COOH COOH

History
Discovery
The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander
Fleming in 1928. He showed that, if Penicillium notatum were grown in the appropriate
substrate, it would exude a substance with antibiotic properties, which he dubbed penicillin.
This serendipitous observation began the modern era of antibiotic discovery. The development
of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter
Florey together with the German Nobel laureate Ernst Chain and the English biochemist
Norman Heatley.
However, several others reported the bacteriostatic effects of Penicillium earlier than Fleming.
The use of bread with a blue mould (presumably penicillium) as a means of treating suppurating
wounds was a staple of folk medicine in Europe since the Middle Ages. The first published
reference appears in the publication of the Royal Society in 1875, by John Tyndall.[13] Ernest
Duchesne documented it in an 1897 paper, which was not accepted by the Institut Pasteur
because of his youth. In March 2000, doctors at the San Juan de Dios Hospital in San José, Costa
Rica published the manuscripts of the Costa Rican scientist and medical doctor Clodomiro
(Clorito) Picado Twight (1887–1944). They reported Picado's observations on the inhibitory
actions of fungi of the genus Penicillium between 1915 and 1927. Picado reported his discovery
to the Paris Academy of Sciences, yet did not patent it, even though his investigations started
years before Fleming's. Joseph Lister was experimenting with penicillum in 1871 for his Aseptic
surgery. He found that it weakened the microbes but then he dismissed the fungi.
These early investigations could not have yielded more intellectual ferment in antibiotic theory
because they not only occurred in practical obscurity, but also because at the time of their
earliest observation, infectious agent theory was not widespread in understanding, nor fully
accepted as medical science fact.
Sanitation/sterilization measures and methods were heuristically known to limit the outbreak
and spread of disease. However, the actual mechanism of what the specific parasite, bacteria,
or virus, agents were, their vectors and mechanisms of transmission & biological attack, how
they progressed in the body at the cellular level, and the bio-chemical mechanism of their
natural course in the bodies of living organisms was wholly unknown, and was unimaginable to
the minds of 19th century medical science and medical practice.
With the rise in the late 19th century of a rigorous fundamental investigative scientific method
and practices in all of the physical sciences, the anecdotal heuristic information regarding
“cures” stemming from the application of natural agents against the progress of disease could
be put to rigorous examination. This work led to the concurrent discovery of how living
organisms receive infection, how they manage infections once they have begun; and, most
importantly (in penicillin’s case) what agents, natural and man-made could do, to affect the
progress of the infection within the living organism.
Fleming recounted that the date of his discovery of penicillin was on the morning of Friday,
September 28, 1928. It was a fortuitous accident: in his laboratory in the basement of St. Mary's
Hospital in London (now part of Imperial College), Fleming noticed a petri dish containing
Staphylococcus plate culture he had mistakenly left open, which was contaminated by blue-
green mould, which had formed a visible growth. There was a halo of inhibited bacterial growth
around the mould. Fleming concluded that the mould was releasing a substance that was
repressing the growth and lysing the bacteria. He grew a pure culture and discovered that it
was a Penicillium mould, now known to be Penicillium notatum. Charles Thom, an American
specialist working at the U.S. Department of Agriculture, was the acknowledged expert, and
Fleming referred the matter to him. Fleming coined the term "penicillin" to describe the filtrate
of a broth culture of the Penicillium mould. Even in these early stages, penicillin was found to
be most effective against Gram-positive bacteria, and ineffective against Gram-negative
organisms and fungi. He expressed initial optimism that penicillin would be a useful
disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, and
noted its laboratory value in the isolation of "Bacillus influenzae" (now Haemophilus
influenzae).[15] After further experiments, Fleming was convinced that penicillin could not last
long enough in the human body to kill pathogenic bacteria, and stopped studying it after 1931.
He restarted clinical trials in 1934, and continued to try to get someone to purify it until 1940.
Medical application
In 1930, Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to use
penicillin to treat sycosis barbae–eruptions in beard follicles, but was unsuccessful, probably
because the drug did not penetrate the skin deeply enough. Moving on to ophthalmia
neonatorum; a gonococcal infection in infants, he achieved the first recorded cure with
penicillin, on November 25, 1930. He then cured four additional patients (one adult and three
infants) of eye infections, failing to cure a fifth.
In 1939, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst
Boris Chain, A. D. Gardner, Norman Heatley, M. Jennings, J. Orr-Ewing and G. Sanders) at the Sir
William Dunn School of Pathology, University of Oxford made significant progress in showing
the in vivo bactericidal action of penicillin. Their attempts to treat humans failed because of
insufficient volumes of penicillin (the first patient treated was Reserve Constable Albert
Alexander), but they proved it harmless and effective on mice.[18]
Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford,
England. These trials continue to be cited by some sources as the first cures using penicillin,
though the Paine trials took place earlier. On March 14, 1942, John Bumstead and Orvan Hess
saved a dying patient's life using penicillin.
Mass production
The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in 1945.
Penicillin has since become the most widely used antibiotic to date, and is still used for many
Gram-positive bacterial infections. A team of Oxford research scientists led by Australian
Howard Florey and including Ernst Boris Chain and Norman Heatley devised a method of mass-
producing the drug. Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for
their work. After World War II, Australia was the first country to make the drug available for
civilian use. Chemist John C. Sheehan at MIT completed the first total synthesis of penicillin and
some of its analogs in the early 1950s, but his methods were not efficient for mass production.
The challenge of mass-producing this drug was daunting. On March 14, 1942, the first patient
was treated for streptococcal septicemia with U.S.-made penicillin produced by Merck & Co.
Half of the total supply produced at the time was used on that one patient. By June 1942, there
was just enough U.S. penicillin available to treat ten patients. A moldy cantaloupe in a Peoria,
Illinois market in 1943 was found to contain the best and highest-quality penicillin after a
worldwide search. The discovery of the cantaloupe, and the results of fermentation research on
corn steep liquor at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the
United States to produce 2.3 million doses in time for the invasion of Normandy in the spring of
1944. Large-scale production resulted from the development of deep-tank fermentation by
chemical engineer Margaret Hutchinson Rousseau.
G. Raymond Rettew made a significant contribution to the American war effort by his
techniques to produce commercial quantities of penicillin. During World War II, penicillin made
a major difference in the number of deaths and amputations caused by infected wounds among
Allied forces, saving an estimated 12%–15% of lives. Availability was severely limited, however,
by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance
of the drug, necessitating frequent dosing. Penicillin is actively excreted, and about 80% of a
penicillin dose is cleared from the body within three to four hours of administration. Indeed,
during the early penicillin era, the drug was so scarce and so highly valued that it became
common to collect the urine from patients being treated, so that the penicillin in the urine
could be isolated and reused.
This was not a satisfactory solution, so researchers looked for a way to slow penicillin excretion.
They hoped to find a molecule that could compete with penicillin for the organic acid
transporter responsible for excretion, such that the transporter would preferentially excrete
the competing molecule and the penicillin would be retained. The uricosuric agent probenecid
proved to be suitable. When probenecid and penicillin are administered together, probenecid
competitively inhibits the excretion of penicillin, increasing penicillin's concentration and
prolonging its activity. Eventually, the advent of mass-production techniques and semi-
synthetic penicillins resolved the supply issues, so this use of probenecid declined.[26]
Probenecid is still useful, however, for certain infections requiring particularly high
concentrations of penicillins.
Developments from penicillin
The narrow range of treatable diseases or spectrum of activity of the penicillins, along with the
poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of
penicillin that could treat a wider range of infections. The isolation of 6-APA, the nucleus of
penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements
over benzylpenicillin (bioavailability, spectrum, stability, tolerance).
The first major development was ampicillin, which offered a broader spectrum of activity than
either of the original penicillins. Further development yielded beta-lactamase-resistant
penicillins including flucloxacillin, dicloxacillin and methicillin. These were significant for their
activity against beta-lactamase-producing bacteria species, but are ineffective against the
methicillin-resistant Staphylococcus aureus strains that subsequently emerged.
Another development of the line of true penicillins was the antipseudomonal penicillins, such
as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative
bacteria. However, the usefulness of the beta-lactam ring was such that related antibiotics,
including the mecillinams, the carbapenems and, most important, the cephalosporins, still
retain it at the center of their structures.
Mechanism of action

Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and
breaking down portions of the cell wall as they grow and divide. β-Lactam antibiotics work by
inhibiting the formation of peptidoglycan cross-links in the bacterial cell wall. The β-lactam
moiety (functional group) of penicillin binds to the enzyme (DD-transpeptidase) that links the
peptidoglycan molecules in bacteria. The enzymes that hydrolyze the peptidoglycan cross-links
continue to function, which weakens the cell wall of the bacterium (in other words, the
antibiotic causes cytolysis or death due to osmotic pressure). In addition, the build-up of
peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins,
which further digest the bacteria's existing peptidoglycan.
Gram-positive bacteria are called protoplasts when they lose their cell wall. Gram-negative
bacteria do not lose their cell wall completely and are called spheroplasts after treatment with
penicillin.
Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan
synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing its
disruption of bacterial protein synthesis within the cell. This results in a lowered MBC for
susceptible organisms.
Penicillins, like other β-lactam antibiotics, block not only the division of bacteria, including
cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the
glaucophytes, and the division of chloroplasts of bryophytes. In contrast, they have no effect on
the plastids of the highly developed vascular plants. This supports the endosymbiotic theory of
the evolution of plastid division in land plants.
Variants in clinical use
The term "penicillin" is often used in the generic sense to refer to one of the narrow-spectrum
penicillins, in particular, benzylpenicillin (penicillin G).
Other types include:
 Phenoxymethylpenicillin
 Procaine benzylpenicillin
 Benzathine benzylpenicillin
Adverse effects
Main article: Penicillin drug reaction
Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include
diarrhea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including
candidiasis). Infrequent adverse effects (0.1–1% of patients) include fever, vomiting, erythema,
dermatitis, angioedema, seizures (especially in epileptics), and pseudomembranous colitis.
Production
Penicillin is a secondary metabolite of fungus Penicillium that is produced when growth of the
fungus is inhibited by stress. It is not produced during active growth. Production is also limited
by feedback in the synthesis pathway of penicillin.
α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-Lysine + β-lactam
The by-product L-Lysine inhibits the production of homocitrate, so the presence of exogenous
lysine should be avoided in penicillin production.
The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are
constantly subject to stress and will produce plenty of penicillin. The carbon sources that are
available are also important: Glucose inhibits penicillin, whereas lactose does not. The pH and
the levels of nitrogen, lysine, phosphate, and oxygen of the batches must be controlled
automatically.
Penicillin production emerged as an industry as a direct result of World War II. During the war,
there was an abundance of jobs available in the U.S. on the home front. The War Production
Board was founded to monitor job distribution and production. Penicillin was produced in huge
quantities during the war and the industry prospered. In July 1943, the War Production Board
drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe.
At the time of this plan, 425 million units per year were being produced. As a direct result of the
war and the War Production Board, by June 1945 over 646 billion units per year were being
produced.
CEPHALOSPORIN
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium,
which was previously known as "Cephalosporium".
Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.

Structure of the classical cephalosporins

History
Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium

from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu. He noticed that these
cultures produced substances that were effective against Salmonella typhi, the cause of typhoid
fever, which had beta-lactamase. Guy Newton and Edward Abraham at the Sir William Dunn
School of Pathology at the University of Oxford isolated cephalosporin C. The cephalosporin
nucleus, 7-aminocephalosporanic acid (7-ACA), was derived from cephalosporin C and proved
to be analogous to the penicillin nucleus 6-aminopenicillanic acid, but it was not sufficiently
potent for clinical use. Modification of the 7-ACA side-chains resulted in the development of
useful antibiotic agents, and the first agent cephalothin (cefalotin) was launched by Eli Lilly and
Company in 1964.
Mechanism of action
Cephalosporins are bactericidal and have the same mode of action as other beta-lactam
antibiotics (such as penicillins) but are less susceptible to penicillinases. Cephalosporins disrupt
the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is
important for cell wall structural integrity. The final transpeptidation step in the synthesis of the
peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs). PBPs
bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the
peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking
of peptidoglycan.
Clinical use
Indications
Cephalosporins are indicated for the prophylaxis and treatment of infections caused by bacteria
susceptible to this particular form of antibiotic. First-generation cephalosporins are
predominantly active against Gram-positive bacteria, and successive generations have
increased activity against Gram-negative bacteria (albeit often with reduced activity against
Gram-positive organisms).
Adverse effects
Common adverse drug reactions (ADRs) (≥1% of patients) associated with the cephalosporin
therapy include: diarrhea, nausea, rash, electrolyte disturbances, and/or pain and inflammation
at injection site. Infrequent ADRs (0.1–1% of patients) include: vomiting, headache, dizziness,

oral and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, and/or
fever.
The commonly quoted figure of 10% of patients with allergic hypersensitivity to penicillins
and/or carbapenems also having cross-reactivity with cephalosporins originated from a 1975
study looking at the original cephalosporins, and subsequent "safety first" policy meant this was
widely quoted and assumed to apply to all members of the group. Hence it was commonly
stated that they are contraindicated in patients with a history of severe, immediate allergic
reactions (urticaria, anaphylaxis, interstitial nephritis, etc.) to penicillins, carbapenems or
cephalosporins. This, however, should be viewed in the light of recent epidemiological work
suggesting that, for many second-generation (or later) cephalosporins, the cross-reactivity rate
with penicillin is much lower, having no significantly increased risk of reactivity in the studies
examined. The British National Formulary previously issued blanket warnings of 10% cross
reactivity, but, since the September 2008 edition, suggests in the absence of suitable
alternatives that oral cefixime or cefuroxime and injectable cefotaxime, ceftazidine, and
ceftriaxone can be used with caution, but to avoid cefaclor, cefadrocil, cefalexin, and cefradine.
Several cephalosporins are associated with hypoprothrombinemia and a disulfiram-like reaction
with ethanol. These include latamoxef, cefmenoxime, moxalactam, cefoperazone,
cefamandole, cefmetazole, and cefotetan. This is thought to be due to the N-
methylthiotetrazole (NMTT) side-chain of these cephalosporins, which blocks the enzyme
vitamin K epoxide reductase (likely causing hypothrombinemia) and aldehyde dehydrogenase
(causing alcohol intolerance).
Classification
The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are
sometimes grouped into "generations" by their antimicrobial properties. The first
cephalosporins were designated first-generation cephalosporins, whereas, later, more
extended-spectrum cephalosporins were classified as second-generation cephalosporins. Each
newer generation of cephalosporins has significantly greater Gram-negative antimicrobial
properties than the preceding generation, in most cases with decreased activity against Gram-
positive organisms. Fourth-generation cephalosporins, however, have true broad-spectrum
activity.
The classification of cephalosporins into "generations" is commonly practiced, although the
exact categorization of cephalosporins is often imprecise. For example, the fourth generation of
cephalosporins is not recognized as such, in Japan.[citation needed] In Japan, cefaclor is classed as a
first-generation cephalosporin, even though in the United States it is a second-generation one;
and cefbuperazone, cefminox, and cefotetan are classed as second-generation cephalosporins.
Cefmetazole and cefoxitin are classed as third-generation cephems. Flomoxef, latamoxef are in
a new class called oxacephems.
Most first-generation cephalosporins were originally spelled "ceph-" in English-speaking
countries. This continues to be the preferred spelling in the United States and Australia, while
European countries (including the United Kingdom) have adopted the International
Nonproprietary Names, which are always spelled "cef-". Newer first-generation cephalosporins
and all cephalosporins of later generations are spelled "cef-", even in the United States.
Some state that, although cephalosporins can be divided into five or even six generations, the
usefulness of this organization system is of limited clinical relevance.
Fourth generation Cephalosporins as of March, 2007 were considered to be "a class of highly
potent antibiotics that are among medicine's last defenses against several serious human
infections" according to the Washington Post.
Members Description
Gram positive: Activity against penicillinase-
producing, methicillin-susceptible
Cefacetrile (cephacetrile), Cefadroxil
staphylococci and streptococci (though they
(cefadroxyl; Duricef), Cephalexin (cephalexin;
are not the drugs of choice for such
Keflex), Cefaloglycin (cephaloglycin),
infections). No activity against methicillin-
Cefalonium (cephalonium), Cefaloridine
resistant staphylococci or enterococci.
1 (cephaloradine), Cefalotin (cephalothin;
Gram negative: Activity against Proteus
Keflin), Cefapirin (cephapirin; Cefadryl),
mirabilis, some Escherichia coli, and Klebsiella
Cefatrizine, Cefazaflur, Cefazedone, Cefazolin
pneumoniae ("PEcK"), but have no activity
(cephazolin; Ancef, Kefzol), Cefradine
against Bacteroides fragilis, Pseudomonas,
(cephradine; Velosef), Cefroxadine, Ceftezole.
Acinetobacter, Enterobacter, indole-positive
Proteus, or Serratia.
Cefaclor (Ceclor, Distaclor, Keflor, Raniclor),
Cefonicid (Monocid), Cefprozil (cefproxil;
Cefzil), Cefuroxime (Zefu, Zinnat, Zinacef,
Ceftin, Biofuroksym,[13] Xorimax), Cefuzonam.
Gram positive: Less than first generation.
Second generation cephalosporins with
Gram negative: Greater than first generation:
antianaerobe activity: Cefmetazole, Cefotetan,
2 HEN (Haemophilus influenzae, Enterobacter
Cefoxitin. The following cephems are also
aerogenes and some Neisseria + the PEcK
sometimes grouped with second-generation
described above.
cephalosporins: Carbacephems: loracarbef
(Lorabid); Cephamycins: cefbuperazone,
cefmetazole (Zefazone), cefminox, cefotetan
(Cefotan), cefoxitin (Mefoxin).
Cefcapene, Cefdaloxime, Cefdinir (Zinir, Gram positive: Some members of this group
Omnicef, Kefnir), Cefditoren, Cefetamet, (in particular, those available in an oral
Cefixime (Zifi, Suprax), Cefmenoxime, formulation, and those with anti-
3 Cefodizime, Cefotaxime (Claforan), Cefovecin pseudomonal activity) have decreased activity
(Convenia), Cefpimizole, Cefpodoxime (Vantin, against Gram-positive organisms.
PECEF), Cefteram, Ceftibuten (Cedax), Gram negative: Third-generation
Ceftiofur, Ceftiolene, Ceftizoxime (Cefizox), cephalosporins have a broad spectrum of

Ceftriaxone (Rocephin). Third-generation activity and further increased activity against
cephalosporins with antipseudomonal activity: Gram-negative organisms. They may be
Cefoperazone (Cefobid), Ceftazidime (Fortum, particularly useful in treating hospital-
Fortaz). The following cephems are also acquired infections, although increasing levels
sometimes grouped with third-generation of extended-spectrum beta-lactamases are
cephalosporins: Oxacephems: latamoxef reducing the clinical utility of this class of
(moxalactam). antibiotics. They are also able to penetrate the
CNS, making them useful against meningitis
caused by pneumococci, meningococci, H.
influenzae, and susceptible E. coli, Klebsiella,
and penicillin-resistant N. gonorrhoeae. Since
2007, third-generation cephalosporins
(ceftriaxone or cefixime) have been the only
recommended treatment for gonorrhea in the
United States.[14]
Gram positive: They are extended-spectrum
agents with similar activity against Gram-
positive organisms as first-generation
cephalosporins.
Cefclidine, Cefepime (Maxipime), Gram negative: Fourth-generation
Cefluprenam, Cefoselis, Cefozopran, cephalosporins are zwitterions that can
Cefpirome (Cefrom), Cefquinome. The penetrate the outer membrane of Gram
4
following cephems are also sometimes negative bacteria. They also have a greater
grouped with fourth-generation resistance to beta-lactamases than the third-
cephalosporins: Oxacephems: flomoxef generation cephalosporins. Many can cross
the blood-brain barrier and are effective in
meningitis. They are also used against
Pseudomonas aeruginosa.
Ceftobiprole has been described as "fifth-
generation" cephalosporin, though
acceptance for this terminology is not
universal. Ceftobiprole (and the soluble
5 Ceftobiprole, Ceftaroline prodrug medocaril) are on the FDA fast-track.
Ceftobiprole has powerful antipseudomonal
characteristics and appears to be less
susceptible to development of resistance.
Ceftaroline has also been described as "fifth-

generation" cephalosporin.
These cephems have progressed far enough to be named, but have not been assigned to a
particular generation: Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole,
Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide,
Cefuracetime
SULFONAMIDE (MEDICINE)
Sulfonamide is the basis of several groups of drugs. The original antibacterial sulfonamides
(sometimes called simply sulfa drugs) are synthetic antimicrobial agents that contain the
sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the
anticonvulsant sultiame. The sulfonylureas and thiazide diuretics are newer drug groups based
on the antibacterial sulfonamides.
Sulfa allergies are common, hence medications containing sulfonamides are prescribed
carefully. It is important to make a distinction between sulfa drugs and other sulfur-containing
drugs and additives, such as sulfates and sulfites, which are chemically unrelated to the
sulfonamide group, and do not cause the same hypersensitivity reactions seen in the
sulfonamides.
Sulfonamide functional group

Antimicrobial (Dihydropteroate synthetase inhibitor)
In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme
dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis.
Other uses
The sulfonamide chemical moiety is also present in other medications that are not
antimicrobials, including thiazide diuretics (including hydrochlorothiazide, metolazone, and
indapamide, among others), loop diuretics (including furosemide, bumetanide and torsemide)
sulfonylureas (including glipizide, glyburide, among others), some COX-2 inhibitors (e. g.
celecoxib) and acetazolamide.
Sulfasalazine, in addition to its use as an antibiotic, is also utilized in the treatment of
inflammatory bowel disease.
History

Sulfonamide drugs were the first antimicrobial drugs, and paved the way for the antibiotic
revolution in medicine. The first sulfonamide, trade named Prontosil, was actually a prodrug.
Experiments with Prontosil began in 1932 in the laboratories of Bayer AG, at that time a
component of the huge German chemical trust IG Farben. The Bayer team believed that coal-
tar dyes able to preferentially bind to bacteria and parasites might be used to target harmful
organisms in the body. After years of fruitless trial-and-error work on hundreds of dyes, a team
led by physician/researcher Gerhard Domagk (working under the general direction of Farben
executive Heinrich Hoerlein) finally found one that worked: a red dye synthesized by Bayer
chemist Josef Klarer that had remarkable effects on stopping some bacterial infections in mice.
The first official communication about the breakthrough discovery was not published until
1935, more than two years after the drug was patented by Klarer and his research partner Fritz
Mietzsch. Prontosil, as Bayer named the new drug, was the first medicine ever discovered that
could effectively treat a range of bacterial infections inside the body. It had a strong protective
action against infections caused by streptococci, including blood infections, childbed fever, and
erysipelas, and a lesser effect on infections caused by other cocci. However, it had no effect at
all in the test tube, exerting its antibacterial action only in live animals. Later it was accidentally
discovered by a French research team, led by Ernest Fourneau (French), at the Pasteur Institute
that the drug was metabolized into two pieces inside the body, releasing from the inactive dye
portion a smaller, colorless, active compound called sulfanilamide. The discovery helped
establish the concept of "bioactivation" and dashed the German corporation's dreams of
enormous profit; the active molecule sulfanilamide (or sulfa) had first been synthesized in 1906
and was widely used in the dye-making industry; its patent had since expired and the drug was
available to anyone.
The result was a sulfa craze. For several years in the late 1930s, hundreds of manufacturers
produced tens of thousands of tons of myriad forms of sulfa. This and nonexistent testing
requirements led to the Elixir Sulfanilamide disaster in the fall of 1937, during which at least
100 people were poisoned with diethylene glycol. This led to the passage of the Federal Food,
Drug, and Cosmetic Act in 1938. As the first and only effective antibiotic available in the years
before penicillin, sulfa drugs continued to thrive through the early years of World War II. They
are credited with saving the lives of tens of thousands of patients including Franklin Delano
Roosevelt, Jr. (son of President Franklin Delano Roosevelt) (in 1936) and Winston Churchill.
Sulfa had a central role in preventing wound infections during the war. American soldiers were
issued a first-aid kit containing sulfa pills and powder and were told to sprinkle it on any open
wound.
During the years 1942 to 1943, Nazi doctors conducted sulfanilamide experiments on prisoners
in concentration camps.
The sulfanilamide compound is more active in the protonated form, which in case of the acid
works better in a basic environment. The solubility of the drug is very low and sometimes can
crystallize in the kidneys, due to its first pKa of around 10. This is a very painful experience so
patients are told to take the medication with copious amounts of water. Newer compounds
have a pKa of around 5–6 so the problem is avoided.
Many thousands of molecules containing the sulfanilamide structure have been created since
its discovery (by one account, over 5,400 permutations by 1945), yielding improved
formulations with greater effectiveness and less toxicity. Sulfa drugs are still widely used for

conditions such as acne and urinary tract infections, and are receiving renewed interest for the
treatment of infections caused by bacteria resistant to other antibiotics.
Sulpha is an alternate (British English) spelling of the common name for sulfonamide
antibiotics.
Preparation
Sulfonamides are prepared by the reaction of a sulfonyl chloride with ammonia or an amine.
Certain sulfonamides (sulfadiazine or sulfamethoxazole) are sometimes mixed with the drug
trimethoprim, which acts against dihydrofolate reductase.
List of sulfonamides
Antibiotics / Dihydropteroate synthetase inhibitors
Short-acting
 Sulfamethoxazole
 Sulfisomidine (also known as sulfaisodimidine)
 Sulfanilamides (e.g. sulfadiazine, sulfamethoxazole)
Intermediate-acting
 Sulfacetamide, Sulfadoxine
Diuretics
 Acetazolamide, Bumetanide, Chlorthalidone, Clopamide, Furosemide,
Hydrochlorothiazide (HCT, HCTZ, HZT), Indapamide, Mefruside, Metolazone, Xipamide
Hydrochlorothiazide is a sulfonamide & a thiazide. Furosemide is a sulfonamide.
Ophthalmologicals
 Dichlorphenamide (DCP), Dorzolamide
Anticonvulsants
 Acetazolamide, Ethoxzolamide, Sultiame, Zonisamide
Dermatologicals
 Mafenide
Other
 Celecoxib (COX-2 inhibitor)
 Darunavir (Protease Inhibitor)
 Probenecid (PBN)
 Sulfasalazine (SSZ)
 Sumatriptan (SMT)
Side effects
Patient Suffering from Stevens–Johnson syndrome
Sulfonamides have the potential to cause a variety of untoward reactions, including urinary
tract disorders, haemopoietic disorders, porphyria and hypersensitivity reactions. When used in

large doses, they may cause a strong allergic reaction. Two of the most serious are Stevens
Johnson syndrome and toxic epidermal necrolysis (also known as Lyell syndrome).
Adverse reactions
Approximately 3% of the general population have adverse reactions when treated with
sulfonamide antimicrobials. Of note is the observation that patients with HIV have a much
higher prevalence, at about 60%. People who have a hypersensitivity reaction to one member
of the sulfonamide class are likely to have a similar reaction to others.
Hypersensitivity reactions are less common in non-antibiotic sulfonamides, and, though
controversial, the available evidence suggests those with hypersensitivity to sulfonamide
antibiotics do not have an increased risk of hypersensitivity reaction to the non-antibiotic
agents.
Allergic urticaria on the skin induced by an antibiotic
Two regions of the sulfonamide antibiotic chemical structure are implicated in the
hypersensitivity reactions associated with the class.
 The first is the N1 heterocyclic ring, which causes a type I hypersensitivity reaction.
 The second is the N4 amino nitrogen that, in a stereospecific process, forms reactive
metabolites that cause either direct cytotoxicity or immunologic response.
The non-antibiotic sulfonamides lack both of these structures.
The most common manifestations of a hypersensitivity reaction to sulfa drugs are rash and
hives. However, there are several life-threatening manifestations of hypersensitivity to sulfa
drugs, including Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis,
hemolytic anemia, thrombocytopenia, and fulminant hepatic necrosis, among others.

Sulfonamide (Antibacterial Agents)
H2N
SO2NH 2 SO2NH 2 NH2
NH2 Liver
N
N [H] +
H2N
H2N
H2N Prontosil rubrum Sulfanilamide N
O
O N
COOH S
NH
S
O
O
NH Gut +
N OH H2N
HO N [H] H2N
HOOC Salfasalazine p-amino-salicylic acid Sulfapyridine

H3C
Triple Sulpha
N N N
H2N SO2NHR R= R= R=
- N - N CH3 - N CH3
H3C Sulphadiazine Sulfamerazine Sulfamethazine

O N N N
CH3 CH3
N -
N
R= R= O N - OCH3 -
- OCH3 H3CO
Sulfamethoxazole Sulfisoxazole Sulfadoxine Sulfalene
Sulfa drug Mechanism:-

HO COOH O
O O
N P OH + Dihydropteroate synthase N N NH
HN O X
O P O H2N
H2N N N HO PABA Sulphonamides H N N N
2
H H H
Dihydropteroic acid
COOH
Trimethoprim-sulfamethoxazole
Sulphonamides are co-administered with dihydrofolate reductase inhibitors such as

trimethoprim and sulphamethoxazole is known as cotrimoxazole is very useful drug
combinations because both drugs act at different phases with synergistic effect.
Trimethoprim-sulfamethoxazole
Combination of
Trimethoprim Dihydrofolate reductase inhibitor

(16.7%)
Sulfamethoxazole Sulfonamide antibiotic (83.3%)
Trimethoprim-sulfamethoxazole or Co-trimoxazole (abbreviated SXT, TMP-SMX, TMP-SMZ or

TMP-sulfa) is a sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole, in
the ratio of 1 to 5, used in the treatment of a variety of bacterial infections. The name co-
trimoxazole is the British Approved Name, and has been marketed worldwide under many
trade names including Septra (GSK), Bactrim (Roche), and various generic preparations. Sources
differ as to whether co-trimoxazole usually is bactericidal or bacteriostatic.

Synergistic action
The synergy between trimethoprim and sulphamethoxazole was first described in a series of in
vitro and in vivo experiments published in the late 1960s. Trimethoprim and sulfamethoxazole
have a greater effect when given together than when given separately; the reason is because
they inhibit successive steps in the folate synthesis pathway (see diagram below).
It is unclear whether this synergy occurs at doses used in humans, because, at the
concentrations seen in blood and tissues, the ratio of trimethoprim to sulphamethoxazole is
1:20,[5] which is less than the 1:5 ratio needed in vitro for synergy to occur.
Tetrahydrofolate synthesis pathway

Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate synthetase.
Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and, thus,
are competitive inhibitors of the enzyme, inhibiting the production of dihydropteroic acid.
Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting
synthesis of tetrahydrofolic acid.
Folic acid is an essential precursor in the de novo synthesis of the DNA nucleosides thymidine
and uridine. Bacteria are unable to take up folic acid from the environment (i.e., the infection
host) and, thus, are dependent on their own de novo synthesis - inhibition of the enzyme
starves the bacteria of two bases necessary for DNA replication and transcription.
Clinical indications
Co-trimoxazole was claimed to be more effective than either of its components individually in
treating bacterial infections, although this was later disputed. Along with its associated greater
incidence of adverse effects including allergic responses (see below), its widespread use has
been restricted in many countries to very specific circumstances where its improved efficacy is
demonstrated. It may be effective in a variety of upper and lower respiratory tract infections,
renal and urinary tract infections, gastrointestinal tract infections, skin and wound infections,
septicaemias and other infections caused by sensitive organisms. The global problem of
advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole in
various settings more recently.[8]
Specific indications for its use include:
HIV
Being an antibiotic, co-trimoxazole does not have any activity against HIV itself, but it is often
prescribed to immunocompromised patients as Pneumocystis jiroveci pneumonia prophylaxis.
Bacterial
 infections caused by Listeria monocytogenes, Nocardia spp., Stenotrophomonas
maltophilia (Zanthomonas maltophilia)
 Staphylococcus saprophyticus infections presenting as urinary tract infection or cystitis
 melioidosis
 shigellosis
 Whipple's disease
 traveller's diarrhea
Protozoan
 Isosporiasis
 prophylaxis of cerebral toxoplasmosis in HIV patients
 Cyclospora cayetanensis
Fungal
 treatment and prophylaxis of pneumonia caused by Pneumocystis jirovecii (formerly
identified as P. carinii and commonly seen in immunocompromised patients including
those suffering from cancer or HIV/AIDS)
Safety
There has been some concern about its use, however, since it has been associated with both
frequent mild allergic reactions and serious adverse effects including Stevens-Johnson
syndrome, myelosuppression, mydriasis, agranulocytosis, as well as severe liver damage
(cholestatic hepatosis, hepatitis, liver necrosis, fulminant liver failure).[citation needed] Due to
displacement of bilirubin from albumin, there is an increased risk of kernicterus in the newborn
during the last 6 weeks of pregnancy. Also renal impairment up to acute renal failure and anuria
have been reported. These side-effects are seen especially in the elderly and may be fatal.
(Joint Formulary Committee, 2004). Both Folic acid and Folinic acid were found equally effective
in reducing the adverse effects of TMP-SMX, so unless new evidence is found for Folinic acid
that shows it is more effective than the cheaper Folic acid, Folic acid will continue to be the
preferred treatment method.
In some countries, co-trimoxazole has been withdrawn due to these toxic effects.


TETRACYCLINE ANTIBIOTICS
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been
reduced with the onset of bacterial resistance. Despite this, they remain the treatment of
choice for some specific indications.
They are so named for their four (“tetra-”) hydrocarbon rings (“-cycl-”) derivation (“-ine”). To be
specific, they are defined as "a subclass of polyketides having an octahydrotetracene-2-
carboxamide skeleton". They are collectively known as "derivatives of polycyclic naphthacene
carboxamide".
N(CH 3)2 OH N(CH 3)2
R X Y X Y
7 5 H 4 7 5 H 4
OH OH
8 6 8 6
3 3
2 2
9 9
10 11 CONH 2 10 11 12 1
CONH 2
12
HO 1 HO
OH O HO O OH O HO O
Tetracycline, R = H, X = OH, Y = CH3 Oxytetracycline, X = OH, Y = CH3
Demeclocycline, R = Cl, X = OH, Y = H Methacycline, X = Y = CH2

Minocycline, R = N(CH3)2, X = Y = H Doxycycline, X = H, Y = CH3
Sanocycline, R = X = Y = H
History
The first member of the group to be discovered is Chlortetracycline (Aureomycin) in the late
1940s by Dr. Benjamin Duggar, a scientist employed by Lederle Laboratories who derived the
substance from a golden-colored, fungus-like, soil-dwelling bacterium named Streptomyces
aureofaciens. Oxytetracycline (Terramycin) was discovered shortly afterwards by AC Finlay et
al.; it came from a similar soil bacterium named Streptomyces rimosus. Robert Burns
Woodward determined the structure of Oxytetracycline enabling Lloyd H. Conover to
successfully produce tetracycline itself as a synthetic product. The development of many
chemically altered antibiotics formed this group. In June 2005, tigecycline, the first member of a
new subgroup of tetracyclines named glycylcyclines, was introduced to treat infections that are
resistant to other antimicrobics including conventional tetracyclines. While tigecycline is the
first tetracycline approved in over 20 years, other, newer versions of tetracyclines are currently
in human clinical trials.
Mechanism of action
Tetracycline antibiotics are protein synthesis inhibitors, inhibiting the binding of aminoacyl-
tRNA to the mRNA-ribosome complex. They do so mainly by binding to the 30S ribosomal
subunit in the mRNA translation complex.
Tetracyclines also have been found to inhibit matrix metalloproteinases. This mechanism does
not add to their antibiotic effects, but has led to extensive research on chemically modified

tetracyclines or CMTs (like incyclinide) for the treatmet of rosacea, acne, and various types of
neoplasms. Since incyclinide was announced to be ineffective for rosacea in September 2007,
no drugs of this group will be marketed in the near-future.
Mechanism and resistance

Tetracycline inhibits cell growth by inhibiting translation. It binds to the 16S part of the 30S
ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the
ribosome. The binding is reversible in nature.
Cells become resistant to tetracycline by at least three mechanisms: enzymatic inactivation of
tetracycline, efflux, and ribosomal protection. Inactivation is the rarest type of resistance,
where an acetyl group is added to the molecule, causing inactivation of the drug. In efflux, a
resistance gene encodes a membrane protein that actively pumps tetracycline out of the cell.
This is the mechanism of action of the tetracycline resistance gene on the artificial plasmid
pBR322. In ribosomal protection, a resistance gene encodes a protein that can have several
effects, depending on what gene is transferred. Six classes of ribosomal protection
genes/proteins have been found, all with high sequence homology, suggesting a common
evolutionary ancestor.
Possible mechanisms of action of these protective proteins include:
1. blocking tetracyclines from binding to the ribosome
2. binding to the ribosome and distorting the structure to still allow t-RNA binding while
tetracycline is bound
3. binding to the ribosome and dislodging tetracycline.
All of these changes to ribosomes are reversible (non-covalent) because ribosomes isolated
from both tetracycline-resistant and susceptible organisms bind tetracycline equally well in
vitro.
Indication
Tetracyclines are generally used in the treatment of infections of the respiratory tract, sinuses,
middle ear, urinary tract, and intestines, and is used in the treatment of gonorrhoea, especially
in patients allergic to β-lactams and macrolides; however, their use for these indications is less
popular than it once was due to widespread resistance development in the causative
organisms.
Their most common current use is in the treatment of moderately severe acne and rosacea
(tetracycline, oxytetracycline, doxycycline, or minocycline).
Doxycycline is also used as a prophylactic treatment for infection by Bacillus anthracis (anthrax)
and is effective against Yersinia pestis, the infectious agent of bubonic plague. It is also used for
malaria treatment and prophylaxis, as well as treating elephantiasis.
Tetracyclines remain the treatment of choice for infections caused by chlamydia (trachoma,
psittacosis, salpingitis, urethritis, and L. venereum infection), Rickettsia (typhus, Rocky
Mountain spotted fever), brucellosis, and spirochetal infections (borreliosis, syphilis, and Lyme
disease). In addition, they may be used to treat anthrax, plague, tularemia, and Legionnaires'
disease.
They may have a role in reducing the duration and severity of cholera, although drug-resistance
is occurring, and their effects on overall mortality is questioned.
Demeclocycline has an additional use in the treatment of SIADH.
Tetracycline derivatives are currently being investigated for the treatment of certain
inflammatory disorders.
Administration
When ingested, it is usually recommended that the more water-soluble, short-acting
tetracyclines (plain tetracycline, chlortetracycline, Oxytetracycline, demeclocycline and
methacycline) be taken with a full glass of water, either two hours after eating, or two hours
before eating. This is partly because most tetracyclines bind with food and also easily with
magnesium, aluminium, iron, and calcium, which reduces their ability to be completely
absorbed by the body. Dairy products, antacids, or preparations containing iron are particularly
recommended to be avoided near the time of taking the drug. Partial exceptions to these rules
occur for doxycycline and minocycline, which may be taken with food (though not iron,
antacids, or calcium supplements). Minocycline, can be taken with dairy products because it
does not chelate calcium as readily, although dairy products do decrease absorption of
minocycline slightly.
Cautions
Tetracyclines should be used with caution in those with liver impairment and those that are
soluble in water and urine worsen renal failure (this is not true of the lipid soluble agents
doxycycline and minocycline). They may increase muscle weakness in myasthenia gravis and
exacerbate systemic lupus erythematosus. Antacids reduce the absorption of all tetracyclines,
and dairy products reduce absorption greatly for all but minocycline.
The breakdown products of tetracyclines are toxic and can cause Fanconi Syndrome, a
potentially fatal disease affecting proximal tubular function in the nephrons of the kidney.
Prescriptions of these drugs should be discarded once expired.
It was once believed that tetracycline antibiotics impair the effectiveness of many types of
hormonal contraception. Recent research has shown no significant loss of effectiveness in oral
contraceptives while using most tetracyclines. Despite these studies, many physicians still
recommend the use of barrier contraception for people taking any tetracyclines to prevent
unwanted pregnancy.
Contraindications
Tetracycline use should be avoided in pregnant or lactating women, and in children with
developing teeth because they may result in permanent staining (dark yellow-gray teeth with a
darker horizontal band that goes across the top and bottom rows of teeth), and possibly affect
the growth of teeth and bones.
In tetracycline preparation, stability must be considered in order to avoid formation of toxic
epi-anhydrotetracyclines.
Side-effects
Side-effects from tetracyclines are not always common, but of particular note is possible
photosensitive allergic reaction that increases the risk of sunburn under exposure to UV light
from the sun or other sources. This may be of particular importance for those intending to take
on vacations long-term doxycyline as a malaria prophylaxis.
They may cause stomach or bowel upsets, and, on rarely occasions, allergic reactions. Very
rarely, severe headache and vision problems may be signs of dangerous secondary intracranial
hypertension, also known as pseudotumor cerebri.

Tetracyclines are teratogens due to the likelihood of causing teeth discolouration in the fetus as
they develop in infancy. For this same reason, tetracyclines are contraindicated for use in
children under 8 years of age. They are, however, safe to use in the first 18 weeks of pregnancy.
Some patients taking tetracyclines require medical supervision because they can cause
steatosis and hepatotoxicity.
Examples of tetracyclines
According to source:
 Naturally-occurring
Tetracycline, Chlortetracycline, Oxytetracycline, Demeclocycline
 Semi-synthetic
Doxycycline, Lymecycline, Meclocycline, Methacycline, Minocycline
Rolitetracycline (Prodrug)
According to duration of action:
 Short-acting (Half-life is 6-8 hrs)
Tetracycline, Chlortetracycline, Oxytetracycline
 Intermediate-acting (Half-life is ~12 hrs)
Demeclocycline, Methacycline
 Long-acting (Half-life is 16 hrs or more)
Doxycycline, Minocycline, Tigecycline
Tigecycline may also be considered a tetracycline antibiotic, though it is usually classified as a
glycylcycline antibiotic.
Chloramphenicol
Chloramphenicol
OH Cl
NH
O2N C
Cl
CH2OH O
Chloramphenicol (INN) is a bacteriostatic antimicrobial. It is considered a prototypical broad-

spectrum antibiotic, alongside the tetracyclines.
Chloramphenicol is effective against a wide variety of Gram-positive and Gram-negative
bacteria, including most anaerobic organisms. Due to resistance and safety concerns, it is no
longer a first-line agent for any indication in developed nations, although it is sometimes used
topically for eye infections. Nevertheless, the global problem of advancing bacterial resistance
to newer drugs has led to renewed interest in its use. In low-income countries, chloramphenicol
is still widely used because it is inexpensive and readily available.
The most serious adverse effect associated with chloramphenicol treatment is bone marrow
toxicity, which may occur in two distinct forms: bone marrow suppression, which is a direct
toxic effect of the drug and is usually reversible, and aplastic anemia, which is idiosyncratic
(rare, unpredictable, and unrelated to dose) and generally fatal.
Spectrum of activity

Because it functions by inhibiting bacterial protein synthesis, chloramphenicol has a very broad
spectrum of activity: it is active against Gram-positive bacteria (including most strains of MRSA),
Gram-negative bacteria and anaerobes. It is not active against Pseudomonas aeruginosa,
Chlamydiae, or Enterobacter species. It has some activity against Burkholderia pseudomallei,
but is no longer routinely used to treat infections caused by this organism (it has been
superseded by ceftazidime and meropenem). In the West, chloramphenicol is mostly restricted
to topical uses because of the worries about the risk of aplastic anaemia.
Therapeutic uses
The original indication of chloramphenicol was in the treatment of typhoid, but the now almost
universal presence of multi-drug resistant Salmonella typhi has meant that it is seldom used for
this indication except when the organism is known to be sensitive. Chloramphenicol may be
used as a second-line agent in the treatment of tetracycline-resistant cholera.
Because of its excellent BBB penetration (far superior to any of the cephalosporins),
chloramphenicol remains the first choice treatment for staphylococcal brain abscesses. It is also
useful in the treatment of brain abscesses due to mixed organisms or when the causative
organism is not known.
Chloramphenicol is active against the three main bacterial causes of meningitis: Neisseria
meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. In the West,
chloramphenicol remains the drug of choice in the treatment of meningitis in patients with
severe penicillin or cephalosporin allergy and GPs are recommended to carry intravenous
chloramphenicol in their bag. In low income countries, the WHO recommend that oily
chloramphenicol be used first-line to treat meningitis.
Chloramphenicol has been used in the U.S. in the initial empirical treatment of children with
fever and a petechial rash, when the differential diagnosis includes both Neisseria meningitidis
septicaemia as well as Rocky Mountain spotted fever, pending the results of diagnostic
investigations.
Chloramphenicol is also effective against Enterococcus faecium, which has led to it being
considered for treatment of vancomycin-resistant enterococcus.
Although unpublished, recent research suggests that chloramphenicol could also be applied to
frogs to prevent their widespread destruction from fungal infections. Chloramphenicol has
recently been discovered to be a life-saving cure for chytridiomycosis in amphibians.
Chytridiomycosis is a fungal disease, blamed for the extinction of one-third of the 120 frog
species lost since 1980.
Adverse effects
Aplastic anemia
The most serious side effect of chloramphenicol treatment is aplastic anaemia. This effect is
rare and is generally fatal: there is no treatment and there is no way of predicting who may or
may not get this side effect. The effect usually occurs weeks or months after chloramphenicol
treatment has been stopped and there may be a genetic predisposition. It is not known
whether monitoring the blood counts of patients can prevent the development of aplastic
anaemia, but it is recommended that patients have a blood count checked twice weekly while
on treatment. The highest risk is with oral chloramphenicol (affecting 1 in 24,000–40,000) and
the lowest risk occurs with eye drops (affecting less than 1 in 224,716 prescriptions).

Thiamphenicol is a related compound with a similar spectrum of activity that is available in Italy
and China for human use, and has never been associated with aplastic anaemia. Thiamphenicol
is available in the U.S. and Europe as a veterinary antibiotic, and is not approved for use in
humans.
Bone marrow suppression
It is common for chloramphenicol to cause bone marrow suppression during treatment: this is a
direct toxic effect of the drug on human mitochondria. This effect manifests first as a fall in
hemoglobin levels and occurs quite predictably once a cumulative dose of 20 g has been given.
This effect is fully reversible once the drug is stopped and does not predict future development
of aplastic anaemia.
Leukemia
There is an increased risk of childhood leukemia as demonstrated in a Chinese case-controlled
study, and the risk increases with length of treatment.
Possible Related Adverse Effects Chloramphenicol is particularly toxic to people sensitive to
benzene based preservatives like preservatives 210 and 211. Chloramphenicol poisoning can
cause sensitivity reactions to organic acids and salicylates. Chloramphenicol is also known to
cause tinnitus and balance problems through inner ear damage. It also causes folic acid
depletion resulting in adverse effects to the thyroid, pituitary and prostate through effects on
PABA levels. There may also be links to chronic lymphocytic leukemia(CLL) through folic acid
"depletion" and resultant high levels of folic acid in the mutant lymphocytes that characterize
CLL Chloramphenicol stops the body's production of vitamin D and pregnenolone. This results in
major hormone depletion, including DHEA and testosterone, that can result in death and also
lowers the body's resistance to viral infection. Chloramphenicol can cause testes pain, possibly
through hormone effects. Chinese research shows that chloramphenicol affects motor
neurones. It also affects insulin Igf1 levels and glutamate levels. Both of these conditions are
considered indicative of a type of motor neurone disease. The adverse genetic effects of
chloramphenicol are considered heritable.
Gray baby syndrome
Intravenous chloramphenicol use has been associated with the so called gray baby syndrome.
This phenomenon occurs in newborn infants because they do not yet have fully functional liver
enzymes (i.e. UDP-glucuronyl transferase), and so chloramphenicol remains unmetabolized in
the body. This causes several adverse effects, including hypotension and cyanosis. The
condition can be prevented by using chloramphenicol at the recommended doses and
monitoring blood levels.
Pharmacokinetics
Chloramphenicol is extremely lipid soluble, it remains relatively unbound to protein and is a
small molecule: it has a large apparent volume of distribution of 100 litres and penetrates
effectively into all tissues of the body, including the brain. The concentration achieved in brain
and cerebrospinal fluid (CSF) is around 30 to 50% even when the meninges are not inflamed;
this increases to as high as 89% when the meninges are inflamed.
Chloramphenicol increases the absorption of iron.
Use in special populations
Chloramphenicol is metabolised by the liver to chloramphenicol glucuronate (which is inactive).
In liver impairment, the dose of chloramphenicol must therefore be reduced. There is no
standard dose reduction for chloramphenicol in liver impairment, and the dose should be
adjusted according to measured plasma concentrations. Chloramphenicol is also noted for its
cause of "Gray Baby Syndrome" because of infants lack of the enzyme glucoronyl transferase
which is the main pathway conjugational excretion, which leads to a buildup of the chemical in
infants system- contraindication.
The majority of the chloramphenicol dose is excreted by the kidneys as the inactive metabolite,
chloramphenicol glucuronate. Only a tiny fraction of the chloramphenicol is excreted by the
kidneys unchanged. It is suggested that plasma levels be monitored in patients with renal
impairment, but this is not mandatory. Chloramphenicol succinate ester (the inactive
intravenous form of the drug) is readily excreted unchanged by the kidneys, more so than
chloramphenicol base, and this is the major reason why levels of chloramphenicol in the blood
are much lower when given intravenously than orally.
Chloramphenicol passes into breast milk and should therefore be avoided during breastfeeding
if possible.
Dose monitoring
Plasma levels of chloramphenicol must be monitored in neonates and in patients with
abnormal liver function. It is recommended that plasma levels be monitored in all children
under the age of 4, the elderly and patients with renal failure. Peak levels (1 hour after the dose
is given) should be 15–25 mg/l; trough levels (taken immediately before a dose) should be less
than 15 mg/l. Drug interactions
Administration of chloramphenicol concomitantly with bone marrow depressant drugs is
contraindicated, although concerns over aplastic anaemia associated with ocular
chloramphenicol have largely been discounted.
Chloramphenicol is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in
the liver. Inhibition of CYP2C19 causes decreased metabolism and therefore increased levels of,
for example, antidepressants, antiepileptics and proton pump inhibitors if they are given
concomitantly. Inhibition of CYP3A4 causes increased levels of, for example, calcium channel
blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, azole antifungals,
tricyclic antidepressants, macrolide antibiotics, SSRIs, statins and PDE5 inhibitors. Mechanism of
action
Chloramphenicol is bacteriostatic (that is, it stops bacterial growth). It is a protein synthesis
inhibitor, inhibiting peptidyl transferase activity of the bacterial ribosome, binding to A2451 and
A2452 residues in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond
formation. While chloramphenicol and the macrolide class of antibiotics both interact with
ribosomes, chloramphenicol is not a macrolide. Chloramphenicol directly interferes with
substrate binding, macrolides sterically block the progression of the growing peptide.
Resistance
There are three mechanisms of resistance to chloramphenicol: reduced membrane
permeability, mutation of the 50S ribosomal subunit and elaboration of chloramphenicol
acetyltransferase. It is easy to select for reduced membrane permeability to chloramphenicol in
vitro by serial passage of bacteria, and this is the most common mechanism of low-level
chloramphenicol resistance. High-level resistance is conferred by the cat-gene; this gene codes
for an enzyme called chloramphenicol acetyltransferase which inactivates chloramphenicol by
covalently linking one or two acetyl groups, derived from acetyl-S-coenzyme A, to the hydroxyl
groups on the chloramphenicol molecule. The acetylation prevents chloramphenicol from
binding to the ribosome. Resistance-conferring mutations of the 50S ribosomal subunit are
rare.
Chloramphenicol resistance may be carried on a plasmid that also codes for resistance to other
drugs. One example is the ACCoT plasmid (A=ampicillin, C=chloramphenicol, Co=co-trimoxazole,
T=tetracycline) which mediates multi-drug resistance in typhoid (also called R factors).
Formulations
Chloramphenicol is available as 250 mg capsules or as a liquid (125 mg/5 ml). In some countries,
chloramphenicol is sold as chloramphenicol palmitate ester. Chloramphenicol palmitate ester is
inactive, and is hydrolysed to active chloramphenicol in the small intestine. There is no
difference in bioavailability between chloramphenicol and chloramphenicol palmitate.
The intravenous (IV) preparation of chloramphenicol is the succinate ester, because pure
chloramphenicol does not dissolve in water. This creates a problem: chloramphenicol succinate
ester is an inactive prodrug and must first be hydrolysed to chloramphenicol; the hydrolysis
process is incomplete and 30% of the dose is lost unchanged in the urine, therefore serum
concentrations of chloramphenicol are only 70% of those achieved when chloramphenicol is
given orally. For this reason, the chloramphenicol dose needs to be increased to 75 mg/kg/day
when administered IV in order to achieve levels equivalent to the oral dose. The oral route is
therefore preferred to the intravenous route.
Manufacture of oral chloramphenicol in the U.S. stopped in 1991, because the vast majority of
chloramphenicol-associated cases of aplastic anaemia are associated with the oral preparation.
There is now no oral formulation of chloramphenicol available in the U.S.
Oily
Dose: 100 mg/kg (maximum dose 3 g) as a single intramuscular injection. The dose is repeated
if there is no clinical response after 48 hours. A single injection costs approximately US$5.
Oily chloramphenicol (or chloramphenicol oil suspension) is a long-acting preparation of
chloramphenicol first introduced by Roussel in 1954; marketed as Tifomycine, it was originally
used as a treatment for typhoid. Roussel stopped production of oily chloramphenicol in 1995;
the International Dispensary Association has manufactured it since 1998, first in Malta and then
in India from December 2004.
Oily chloramphenicol is recommended by the World Health Organization (WHO) as the first line
treatment of meningitis in low-income countries and appears on the essential drugs list. It was
first used to treat meningitis in 1975 and there have been numerous studies since
demonstrating its efficacy It is the cheapest treatment available for meningitis (US$5 per
treatment course, compared to US$30 for ampicillin and US$15 for five days of ceftriaxone). It
has the great advantage of requiring only a single injection, whereas ceftriaxone is traditionally
given daily for five days. This recommendation may yet change now that a single dose of
ceftriaxone (cost US$3) has been shown to be equivalent to one dose of oily chloramphenicol.
Oily chloramphenicol is not currently available in the U.S. or Europe.
Eye drops
In the West, chloramphenicol is still widely used in topical preparations (ointments and eye
drops) for the treatment of bacterial conjunctivitis. Isolated cases report of aplastic anaemia
following chloramphenicol eyedrops exist, but the risk is estimated to be less than 1 in 224,716
prescriptions
History
Chloramphenicol was originally derived from the bacterium Streptomyces venezuelae, isolated
by David Gottlieb, & introduced into clinical practice in 1949, under the trade name
Chloromycetin. It was the first antibiotic to be manufactured synthetically on a large scale.

STEREOCHEMISTRY
STEREOISOMERS are isomers which have the same pattern of bonding but with atoms
arranged differently in space. Stereoisomers are also known as geometric isomers but
confusingly this latter term is often used to refer only to 'cis/trans isomers'.There are two
types of stereoisomer:
Enantiomers
two isomers which are mirror images of each other; also known as optical
isomers due to the fact that two enantiomers will rotate plane-polarized light in
equal, but opposite directions. Chirality is (yet) another term for enantiomerism.
Diastereomers
stereoisomers which are not enantiomers.
Stereoisomerism can be caused by:
Stereocenters
if a carbon atom has four different groups attached to it, it will exhibit
enantiomerism. Other causes of enantiomerism include helical structures.
Non-rotation of bonds
the C=C bond cannot rotate and is the most common cause of diastereomerism.
Other causes are cyclic compounds and steric hindrance.
CONFIGURATION AND CONFORMATION

Conformation is the set of possible shapes a molecule can have by means of rotation about
single bonds only. Configuration is the relative position of the atoms in a molecule that can
be changed exclusively by cleaving and forming new chemical bonds. Isomers have different
configurations, although the distinction may be blurred in compounds where steric
hindrance occurs.
NAMING CONVENTIONS
There are three main systems for describing configuration: the oldest, the relative whose
use is now deprecated, and the current, or absolute. The relative configuration description
is still used mainly in glycochemistry. Configuration can also be assigned on the purely
empirical basis of the optical activity.
OPTICAL ACTIVITY : (+) & (-)

An optical isomer can be named by the direction in which it rotates the plane of polarized
light. If an isomer rotates the plane clockwise as seen by a viewer towards whom the light is
traveling, that isomer is labeled (+). Its counterpart is labeled (-). The (+) and (-) isomers
have also been termed d- and l-, respectively (for dextrorotatory and levorotatory). This
labeling is easy to confuse with D- and L-.The fact that an enantiomer can rotate polarised
light clockwise (d- or +- enantiomer) does not relate with the relative configuration (D- or L-)
of it.

RELATIVE CONFIGURATION: D- AND L-
Fischer, whose research interest was in carbohydrate chemistry, took glyceraldehyde (the
simplest sugar, systematic name 2,3-dihydroxyethanal) as a template chiral molecule and
denoted the two possible configurations with D- and L-, which rotated polarised light
clockwise and counterclockwise, respectively.
All other molecules are assigned the D- or L- configuration if the chiral centre can be
formally obtained from glyceraldehyde by substitution. For this reason the D- or L- naming
scheme is called relative configuration.
An optical isomer can be named by the spatial configuration of its atoms. The D/L system
does this by relating the molecule to glyceraldehyde. Glyceraldehyde is chiral itself, and
its two isomers are labeled D and L. Certain chemical manipulations can be performed
on glyceraldehyde without affecting its configuration, and its historical use for this
purpose (possibly combined with its convenience as one of the smallest commonly-used
chiral molecules) has resulted in its use for nomenclature. In this system, compounds are
named by analogy to glyceraldehyde, which generally produces unambiguous designations,
but is easiest to see in the small biomolecules similar to glyceraldehyde.
One example is the amino acid alanine: alanine has two optical isomers, and they are
labeled according to which isomer of glyceraldehyde they come from. Glycine, the amino
acid derived from glyceraldehyde, incidentally, does not retain its optical activity, since its
central carbon is not chiral. Alanine, however, is essentially methylated glycine and shows
optical activity.
The D/L labeling is unrelated to (+)/(-); it does not indicate which enantiomer is
dextrorotatory and which is levorotatory. Rather, it says that the compound's
stereochemistry is related to that of the dextrorotatory or levorotatory enantiomer of
glyceraldehyde. Nine of the nineteen L-amino acids commonly found in proteins are
dextrorotatory (at a wavelength of 589 nm), and D-fructose is also referred to as levulose
because it is levorotatory.
The dextrorotatory isomer of glyceraldehyde is in fact the D isomer, but this was a lucky
guess. At the time this system was established, there was no way to tell which configuration
was dextrorotatory. (If the guess had turned out wrong, the labeling situation would now be
even more confusing.)
A rule of thumb for determining the D/L isomeric form of an amino acid is the "CORN" rule.
The groups:

COOH, R, NH2 and H (where R is an unnamed carbon chain)
are arranged around the chiral center carbon atom. If these groups are arranged counter-
clockwise around the carbon atom, then it is the D-form. If clockwise, it is the L-form.
ABSOLUTE CONFIGURATION: R- AND S-

The absolute configuration system stems from the Cahn-Ingold-Prelog priority rules, which
allow a precise description of a stereocenter without using any reference compound. In fact
the basis is now the atomic number of the stereocenter substituents. The R/S system is
another way to name an optical isomer by its configuration, without involving a reference
molecule such as glyceraldehyde. It labels each chiral center R or S according to a system by
which its ligands are each assigned a priority, according to the Cahn Ingold Prelog priority
rules, based on atomic number.This system labels each chiral center in a molecule (and also
has an extension to chiral molecules not involving chiral centers). It thus has greater
generality than the D/L system, and can label, for example, an (R,R) isomer versus an (R,S)
— diastereomers. The R/S system has no fixed relation to the (+)/(-) system. An R isomer
can be either dextrorotatory or levorotatory, depending on its exact ligands.The R/S system
also has no fixed relation to the D/L system. For example, one of glyceraldehyde's ligands is
a hydroxy group, -OH. If a thiol group, -SH, were swapped in for it, the D/L labeling would,
by its definition, not be affected by the substitution. But this substitution would invert the
molecule's R/S labeling, due to the fact that sulfur's atomic number is higher than carbon's,
whereas oxygen's is lower. [Note: This seems incorrect. Oxygen has a higher atomic number
than carbon.]For this reason, the D/L system remains in common use in certain areas, such
as amino acid and carbohydrate chemistry. It is convenient to have all of the common amino
acids of higher organisms labeled the same way. In D/L, they are all L. In R/S, they are not,
conversely, all S — most are, but cysteine, for example, is R, again because of sulfur's higher
atomic number. The word “racemic” is derived from the Latin word for grape; the term
having its origins in the work of Louis Pasteur who isolated racemic tartaric acid from wine.
CHIRAL COMPOUNDS WITHOUT STEREOCENTERS

It is also possible for a molecule to be chiral without having actual point chirality
(stereocenters). Commonly encountered examples include 1,1'-bi-2-naphthol (BINOL) and
1,3-dichloro-allene which have axial chirality, and (E)-cyclooctene which has planar
chirality.For example, the isomers which are shown by the following figure are different. The
two isomers cannot convert from one to another spontaneously because of restriction of
rotation of double bonds. Other types of chiral compounds without stereocenters (like
restriction of rotation of a single bond because of steric hindrance) also exist. Consider the
following example of the R and S binol molecules:

The biphenyl C-C bond cannot rotate if the X and Y groups cause steric hindrance. This compound
exhibits spiral chirality.
IMPORTANT NAME REACTION

ALDOL CONDENSATION
In some cases, the adducts obtained from the Aldol Addition can easily be converted to α,β-
unsaturated carbonyl compounds, either thermally or under acidic or basic catalysis..
ARNDT-EISTERT SYNTHESIS
The Arndt-Eistert Synthesis allows the formation of homologated carboxylic acids or their
derivatives by reaction of the activated carboxylic acids with diazomethane and subsequent
Wolff-Rearrangement of the intermediate diazoketones in the presence of nucleophiles
such as water, alcohols, or amines

AZO COUPLING
Azo coupling is the most widely used industrial reaction in the production of dyes, lakes and
pigments. Aromatic diazonium ions acts as electrophiles in coupling reactions with activated
aromatics such as anilines or phenols. The substitution normally occurs at the para position,
except when this position is already occupied, in which case ortho position is favoured. The
pH of solution is quite important; it must be mildly acidic or neutral, since no reaction takes
place if the pH is too low.
BAEYER-VILLIGER OXIDATION
The Baeyer-Villiger Oxidation is the oxidative cleavage of a carbon-carbon bond adjacent to

a carbonyl, which converts ketones to esters and cyclic ketones to lactones. The Baeyer-
Villiger can be carried out with peracids, such as MCBPA, or with hydrogen peroxide and a
Lewis acid.so,it is called as oxy-insert reaction.
BAKER-VENKATARAMAN REARRANGEMENT
The base-induced transfer of the ester acyl group in an o-acylated phenol ester, which leads
to a 1,3-diketone. This reaction is related to the Claisen Condensation, and proceeds
through the formation of an enolate, followed by intramolecular acyl transfer

BECKMANN REARRANGEMENT
An acid-induced rearrangement of oximes to give amides.This reaction is related to the

Hofmann and Schmidt Reactions and the Curtius Rearrangement, in that an electropositive
nitrogen is formed that initiates an alkyl migration.
BENZILIC ACID REARRANGEMENT
1,2-Diketones undergo a rearrangement in the presence of strong base to yield α-

hydroxycarboxylic acids. The best yields are obtained when the subject diketones do not
have enolizable protons.
The reaction of a cyclic diketone leads to an interesting ring contraction:
Ketoaldehydes do not react in the same manner, where a hydride shift is preferred
(in Cannizzaro Reaction)
BENZOIN CONDENSATION
The Benzoin Condensation is a coupling reaction between two aldehydes that allows
the preparation of α-hydroxyketones. The first methods were only suitable for the
conversion of aromatic aldehydes

BISCHLER-NAPIERALSKI REACTION
The Bischler-Napieralski Reaction allows the synthesis of 3,4-dihydroisoquinolines from the

β-ethylamides of electron-rich arenes using condensation reagents such as P2O5, POCl3 or
ZnCl2.
BLAISE REACTION
The Blaise Reaction allows the synthesis of β-enamino esters or β-keto esters (depending on
the work-up conditions) via the zinc-mediated reaction of nitriles with α-haloesters.
CANNIZZARO REACTION
This redox disproportionation of non-enolizable aldehydes to carboxylic acids and alcohols is

conducted in concentrated base. α-Keto aldehydes give the product of an intramolecular
disproportionation in excellent yields.
CLAISEN CONDENSATION

The Claisen Condensation between esters containing α-hydrogens, promoted by a base such
as sodium ethoxide, affords β-ketoesters. The driving force is the formation of the stabilized
anion of the β-keto ester. If two different esters are used, an essentially statistical mixture
of all four products is generally obtained, and the preparation does not have high synthetic
utility.
However, if one of the ester partners has enolizable α-hydrogens and the other does not
(e.g., aromatic esters or carbonates), the mixed reaction (or crossed Claisen) can be
synthetically useful. If ketones or nitriles are used as the donor in this condensation
reaction, a β-diketone or a β-ketonitrile is obtained, respectively.
The use of stronger bases, e.g. sodium amide or sodium hydride instead of sodium ethoxide,
often increases the yield.
The intramolecular version is known as Dieckmann Condensation.
CLEMMENSEN REDUCTION
The Clemmensen Reduction allows the deoxygenation of aldehydes or ketones, to produce

the corresponding hydrocarbon. The substrate must be stable to strong acid. The
Clemmensen Reduction is complementary to the Wolff-Kishner Reduction, which is run
under strongly basic conditions. Acid-labile molecules should be reduced by the Wolff-
Kishner protocol.
COPE ELIMINATION
The Cope Reaction of N-oxides, which can easily be prepared in situ from amines with an
oxidant such as peracid, leads to alkenes via a thermally induced syn-elimination in aprotic
solvents
COPE REARRANGEMENT

The Cope Rearrangement is the thermal isomerization of a 1,5-diene leading to a
regioisomeric 1,5-diene. The main product is the thermodynamically more stable
regioisomer. The Oxy-Cope has a hydroxyl substituent on an sp3-hybridized carbon of the
starting isomer.
The driving force for the neutral or anionic Oxy-Cope Rearrangement is that the product is
an enol or enolate (resp.), which can tautomerize to the corresponding carbonyl compound.
This product will not equilibrate back to the other regioisomer.
CURTIUS REARRANGEMENT
The Curtius Rearrangement is the thermal decomposition of carboxylic azides to produce an

isocyanate. These intermediates may be isolated, or their corresponding reaction or
hydrolysis products may be obtained.
The reaction sequence - including subsequent reaction with water which leads to amines - is
named the Curtius Reaction. This reaction is similar to the Schmidt Reaction with acids,
differing in that the acyl azide in the present case is prepared from the acyl halide and an
azide salt.
DARZENS CONDENSATION
The Darzens Reaction is the condensation of a carbonyl compound with an α-halo ester in
the presence of a base to form an α,β-epoxy ester.

DIECKMANN CONDENSATION
The base-catalyzed intramolecular condensation of a diester. The Dieckmann Condensation

works well to produce 5- or 6-membered cyclic ß-keto esters, and is usually effected with
sodium alkoxide in alcoholic solvent.
DIELS-ALDER REACTION
The [4+2]-cycloaddition of a conjugated diene and a dienophile (an alkene or alkyne), an

electrocyclic reaction that involves the 4 π-electrons of the diene and 2 π-electrons of the
dienophile. The driving force of the reaction is the formation of new σ-bonds, which are
energetically more stable than the π-bonds.
In the case of an alkynyl dienophile, the initial adduct can still react as a dienophile if not too
sterically hindered. In addition, either the diene or the dienophile can be substituted with
cumulated double bonds, such as substituted allenes.
With its broad scope and simplicity of operation, the Diels-Alder is the most powerful
synthetic method for unsaturated six-membered rings.
A variant is the hetero-Diels-Alder, in which either the diene or the dienophile contains a
heteroatom, most often nitrogen or oxygen. This alternative constitutes a powerful
synthesis of six-membered ring heterocycles
FAVORSKII REACTION
The rearrangement of cyclopropanones, often obtained as intermediates from the base-

catalyzed reaction of α-halo ketones, leading to carboxylic acids and derivatives.

FISCHER INDOLE SYNTHESIS
The conversion of aryl hydrazones to indoles; requires elevated temperatures and the
addition of Brønsted or Lewis acids. Some interesting enhancements have been published
recently; for example a milder conversion when N-trifluoroacetyl enehydrazines are used as
substrates.
FRIEDEL-CRAFTS ACYLATION
This electrophilic aromatic substitution allows the synthesis of monoacylated products from
the reaction between arenes and acyl chlorides or anhydrides. The products are
deactivated, and do not undergo a second substitution. Normally, a stoichiometric amount
of the Lewis acid catalyst is required, because both the substrate and the product form
complexes.
FRIEDEL-CRAFTS ALKYLATION
This Lewis acid-catalyzed electrophilic aromatic substitution allows the synthesis of

alkylated products via the reaction of arenes with alkyl halides or alkenes. Since alkyl
substituents activate the arene substrate, polyalkylation may occur. A valuable, two-step
alternative is Friedel-Crafts Acylation followed by a carbonyl reduction.

FRIES REARRANGEMENT
The Fries Rearrangement enables the preparation of acyl phenols.
GABRIEL SYNTHESIS
Potassium phthalimide is a -NH2-synthon which allows the preparation of primary amines by

reaction with alkyl halides. After alkylation, the phthalimid is not nucleophile and does not
react anymore. Product is cleaved by reaction with base or hydrazine, which leads to a
stable cyclic product.
GRIGNARD REACTION
The Grignard Reaction is the addition of an organomagnesium halide (Grignard reagent) to a

ketone or aldehyde, to form a tertiary or secondary alcohol, respectively. The reaction with
formaldehyde leads to a primary alcohol.

HANTZSCH DIHYDROPYRIDINE (PYRIDINE) SYNTHESIS
This reaction allows the preparation of dihydropyridine derivatives by condensation of an

aldehyde with two equivalents of a β-ketoester in the presence of ammonia. Subsequent
oxidation (or dehydrogenation) gives pyridine-3,5-dicarboxylates, which may also be
decarboxylated to yield the corresponding pyridines
HELL-VOLHARD-ZELINSKY REACTION
Treatment with bromine and a catalytic amount of phosphorus leads to the selective α-
bromination of carboxylic acids.
HOFMANN ELIMINATION
Sometimes referred to as the Hofmann Degradation. This elimination reaction of alkyl

trimethyl amines proceeds with anti-stereochemistry, and is generally suitable for producing
alkenes with one or two substituents. The reaction follows the Hofmann Rule.
HOFMANN'S RULE

Hofmann's Rule implies that steric effects have the greatest influence on the outcome of
the Hofmann or similar eliminations. The loss of the β-hydrogen occurs preferably from the
most unhindered (least substituted) position [-CH3 > -CH2-R > -CH(R2)]. The product alkene
with fewer substitutents will predominate. Ester Pyrolysis also obeys this preference, and
the Hofmann Rule is generally followed whenever a reaction passes through a cyclic
transition state.
Hofmann's Rule is valid for all intramolecular eliminations and for the Hofmann Elimination.
Most bimolecular eliminations will follow Saytzeff's Rule.
WILLGERODT-KINDLER REACTION
The Willgerodt Reaction allows the synthesis of amides from aryl ketones under the
influence of a secondary amine and a thiating agent.
KOLBE- SCHMITT REACTION
A base-promoted carboxylation of phenols that allows the synthesis of salicylic acid

derivatives.
MANNICH REACTION
This multi-component condensation of a nonenolizable aldehyde, a primary or secondary

amine and an enolizable carbonyl compound affords aminomethylated products. The
iminium derivative of the aldehyde is the acceptor in the reaction.The involvement of the

Mannich Reaction has been proposed in many biosynthetic pathways, especially for
alkaloids
MARKOVNIKOV'S RULE
Markovnikov Rule predicts the regiochemistry of HX addition to unsymmetrically

substituted alkenes.The halide component of HX bonds preferentially at the more highly
substituted carbon, whereas the hydrogen prefers the carbon which already contains more
hydrogens.
ANTI-MARKOVNIKOV
Some reactions do not follow Markovnikov's Rule, and anti-Markovnikov products are
isolated. This is a feature for example of radical induced additions of HX and
of Hydroboration.
MICHAEL ADDITION
The 1,4-addition (or conjugate addition) of resonance-stabilized carbanions. The Michael

Addition is thermodynamically controlled; the reaction donors are active methylenes such
as malonates and nitroalkanes, and the acceptors are activated olefins such as α,β-
unsaturated carbonyl compounds.
Examples:
donors

acceptors
NEF REACTION
The conversion of nitro compounds into carbonyls is known as the Nef Reaction.
NUCLEOPHILIC SUBSTITUTION (SN1-SN2)
Nucleophilic substitution is the reaction of an electron pair donor (the nucleophile, Nu) with
an electron pair acceptor (the electrophile). An sp3-hybridized electrophile must have a
leaving group (X) in order for the reaction to take place.
Mechanism of Nucleophilic Substitution
The term SN2 means that two molecules are involved in the actual transition state:
The departure of the leaving group occurs simultaneously with the backside attack by the
nucleophile. The SN2 reaction thus leads to a predictable configuration of the stereocenter -
it proceeds with inversion (reversal of the configuration).
In the SN1 reaction, a planar carbenium ion is formed first, which then reacts further with
the nucleophile. Since the nucleophile is free to attack from either side, this reaction is
associated with racemization.

In both reactions, the nucleophile competes with the leaving group. Because of this, one
must realize what properties a leaving group should have, and what constitutes a good
nucleophile. For this reason, it is worthwhile to know which factors will determine whether
a reaction follows an SN1 or SN2 pathway.
Very good leaving groups, such as triflate, tosylate and mesylate, stabilize an incipient
negative charge. The delocalization of this charge is reflected in the fact that these ions are
not considered to be nucleophilic.
Hydroxide and alkoxide ions are not good leaving groups; however, they can be activated by
means of Lewis or Brønsted acids.
Epoxides are an exception, since they relieve their ring strain when they undergo
nucleophilic substitution, with activation by acid being optional:

Triflate, tosylate and mesylate are the anions of strong acids. The weak conjugate bases are
poor nucleophiles. Nucleophilicity increases in parallel with the base strength. Thus, amines,
alcohols and alkoxides are very good nucleophiles. Base strength is a rough measure of how
reactive the nonbonding electron pair is; thus, it is not necessary for a nucleophile to be
anionic.
Under substitution conditions, amines proceed all the way to form quaternary salts, which
makes it difficult to control the extent of the reaction.
However, as a nucleophile's base strength and steric hindrance increase, its basicity tends to
be accentuated. If there are abstractable protons at the β-position of the electrophile, an
elimination pathway can compete with the nucleophilic substitution.
An additional factor that plays a role is the character of the solvent. Increasing stabilization
of the nucleophile by the solvent results in decreasing reactivity. Thus, polar protic solvents
will stabilize the chloride and bromide ions through the formation of hydrogen bonds to
these smaller anions. Iodide is a comparatively better nucleophile in these solvents. The
reverse behavior predominates in aprotic polar media.
The solvent also plays an important role in determining which pathway the reaction will
take, SN1 versus SN2. It may safely be assumed that a primary-substituted leaving group will
follow an SN2 pathway in any case, since the formation of the corresponding unstable
primary carbenium ion is disfavored. Reaction by the SN1 pathway is highly probable for
compounds with tertiary substitution, since the corresponding tertiary carbenium ion is
stabilized through hyperconjugation:

The better the solvent stabilizes the ions, the more probable that the reaction will follow an
SN1 pathway (e.g., in polar protic solvents such as water/acetone). The more highly
substituted is the incipient carbenium ion, the more probable that the reaction will follow
an SN1 pathway. The more unreactive the nucleophile, the more probable it becomes that a
reaction with secondary and tertiary electrophiles will follow an SN1 pathway. A weaker
nucleophile is not as effective in the backside attack, since this location is sterically shielded,
especially in the case of tertiary substrates. Carbenium ions are planar and therefore less
sterically hindered, and are naturally more reactive as electrophiles than the uncharged
parent compound.
The hydrolysis of tert-butyl chloride is a typical SN1 reaction:
OZONOLYSIS
CRIEGEE MECHANISM
Ozonolysis allows the cleavage of alkene double bonds by reaction with ozone. Depending
on the work up, different products may be isolated: reductive work-up gives either alcohols
or carbonyl compounds, while oxidative work-up leads to carboxylic acids or ketones.

PINACOL COUPLING REACTION
This reaction involves the reductive homo-coupling of a carbonyl compound to produce a

symmetrically substituted 1,2-diol. The first step is single electron transfer of the carbonyl
bond, which generates radical ion intermediates that couple via carbon-carbon bond
formation to give a 1,2-diol. The example depicted above shows the preparation of pinacol
itself.Pinacol and other highly substituted 1,2-diols tend to undergo dehydration with
rearrangement under acid-catalysis (see Pinacol Rearrangement).
PINACOL REARRANGEMENT
In the conversion that gave its name to this reaction, the acid-catalyzed elimination of water
from pinacol gives t-butyl methyl ketone.
PINNER REACTION
The Pinner Reaction is the partial solvolysis of a nitrile to yield an iminoether. Treatment of
the nitrile with gaseous HCl in a mixture of anhydrous chloroform and an alcohol produces
the imino ether hydrochloride. These salts are known as Pinner Salts, and may react further
with various nucleophiles

PRINS REACTION
The Prins Reaction is the acid-catalyzed of addition aldehydes to alkenes, and gives different
products depending on the reaction conditions. It can be thought of conceptually as the
addition of the elements of the gem-diol carbonyl hydrate of the aldehyde across the
double bond.
An excess of aldehyde and temperatures < 70 °C lead to the formation of acetals. When one
equivalent of aldehyde is used and temperatures are > 70 °C diols or allylic alcohols may be
isolated.
REFORMATSKY REACTION
The formation of ester-stabilized organozinc reagents and their addition to carbonyl

compounds
RITTER REACTION

The acid-induced nucleophilic addition of a nitrile to a carbenium ion, followed by hydrolysis
to the corresponding amid
SANDMEYER REACTION
The substitution of an aromatic amino group is possible via preparation of its diazonium salt
and subsequent displacement with a nucleophile (Cl-, I-, CN-, RS-, HO-). Many Sandmeyer
Reactions proceed under copper(I) catalysis, while the Sandmeyer-type reactions with
thiols, water and potassium iodide don't require catalysis.
The Sandmeyer Reaction is a very important transformation in aromatic chemistry, because

it can result in some substitution patterns that are not achievable by direct
substitution.Fluorination is possible by using the related Schiemann Reaction
SAYTZEFF'S RULE
Saytzeff Rule implies that base-induced eliminations (E2) will lead predominantly to the
olefin in which the double bond is more highly substituted, i.e. that the product distribution
will be controlled by thermodynamics.

The use of sterically hindered bases raises the activation energy barrier for the pathway to
the product predicted by Saytzeff's Rule. Thus, a sterically hindered base will preferentially
react with the least hindered protons, and the product distribution will be controlled by
kinetics
SCHOTTEN-BAUMANN REACTION
The use of added base to drive the equilibrium in the formation of amides from amines and
acid chlorides.
The acylation of amines with carboxylic acid chlorides leads to the production of one
equivalent acid, which will form a salt with unreacted amine and diminish the yield. The
addition of an additional equivalent of base to neutralise this acid is a way to optimise the
conditions. Normally, aqueous base is slowly added to the reaction mixture.
In general, the use of biphasic aqueous basic conditions is often named "Schotten-Baumann
conditions".
STRECKER SYNTHESIS
The Strecker Synthesis is a preparation of α-aminonitriles, which are versatile intermediates

for the synthesis of amino acids via hydrolysis of the nitrile.

SUZUKI COUPLING
The scheme above shows the first published Suzuki Coupling, which is the palladium-
catalysed cross coupling between organoboronic acid and halides. Recent catalyst and
methods developments have broadened the possible applications enormously, so that the
scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and
alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in
place of boronic acids. Some pseudohalides (for example triflates) may also be used as
coupling partners.
SWERN OXIDATION
The Swern Oxidation of alcohols avoids the use of toxic metals such as chromium, and can
be carried out under very mild conditions. This reaction allows the preparation of aldehydes
and ketones from primary and secondary alcohols, resp. . Aldehydes do not react further to
give carboxylic acids. A drawback is the production of the malodorous side product dimethyl
sulphide
ULLMANN REACTION
There are two different transformations referred as the Ullmann Reaction. The "classic"
Ullmann Reaction is the synthesis of symmetric biaryls via copper-catalyzed coupling

VILSMEIER-HAACK REACTION
The Vilsmeier Reaction allows the formylation of electron-rich arenes
WILLIAMSON SYNTHESIS
This method is suitable for the preparation of a wide variety of unsymmetric ethers. The
nucleophilic substitution of halides with alkoxides leads to the desired products.
If the halides are sterically demanding and there are accessible protons in the β-position,
the alkoxide will act as a base, and side products derived from elimination are isolated
instead
WITTIG REACTION
The Wittig Reaction allows the preparation of an alkene by the reaction of an aldehyde or
ketone with the ylide generated from a phosphonium salt. The geometry of the resulting
alkene depends on the reactivity of the ylide. If R is Ph, then the ylide is stabilized and is not
as reactive as when R = alkyl. Stabilized ylides give (E)-alkenes whereas non-stabilized ylides
lead to (Z)-alkenes (see Wittig-Horner Reaction)

WOHL-ZIEGLER REACTION
The bromination of allylic positions with N-bromosuccinimide (NBS) follows a radical

pathway
WOLFF-KISHNER REDUCTION
The reduction of aldehydes and ketones to alkanes. Condensation of the carbonyl

compound with hydrazine forms the hydrazone, and treatment with base induces the
reduction of the carbon coupled with oxidation of the hydrazine to gaseous nitrogen, to
yield the corresponding alkane.
The Clemmensen Reduction can effect a similar conversion under strongly acidic conditions,
and is useful if the starting material is base-labile.

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TEST PAPER-10 PHARMACEUTICAL CHEMISTRY GPAT TEST SERIES BY PHARMAROCKS

GPAT STUDY MATERIAL

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 12

DRUGS AND THEIR ACTIVE METABOLITES

SR.NO. DRUG ACTIVE METABOLITE

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 2

PRODUCTS AND ANIMALS USED FOR BIOASSAYS

SR DRUG PRODUCT ANIMAL

3 Insulin inj, Rabbit

7 Posterior pituitary Chicken

8 Tubocurarine chloride Rabbit

9 Chorionic gonadotropin Male rat

10 Cod liver oil Rachitic rat

11 Heparin sodium Sheep

12 Iron dextran injection Microbial cultures

13 Antiseptic and disinfectant Frog

14 Fungicides and Herbicides Mouse

15 Diphtheria toxoid Rat

17 Insulin inj. Guinea pig

18 Elastomeric closures Plastic containers Guinea pig

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 3

RECOMENDE NEEDLE SIZE FOR VARIOUS INJECTIONS

INJECTIONS GUAGE LENGTH IN INCHES

INTRADERMAL 26G ¼ or 3/8

S.C 26G ½-¾

I.M 24G ¾-1

I.V 22G 1-1/4-1 ½

DRUGS AND THEIR VARIETIES

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 4

DRUG AND THEIR SYNONYMS

SR.NO. DRUG SYNONYMS

1 Cinchona Panama bark

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 5

29 Pale calicher Gambier catechu

NAME OF THE DRUG AND SIDE EFFECTS

SR NO NAME OF THE DRUG SIDE EFFECTS

1 ACE Inhibitors Dry Cough

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 6

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 7

CAPSULE NO & THEIR APPROXIMATE CAPACITY IN mg & ml

PROPORTIONS REQUIRED FOR A PRIMARY EMULSION

TYPE OF OIL OIL: WATER: GUM RATIO

CODE: LPSO (APPLY THIS FOR TWEENS & SPANS)

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 8

Descriptive Term Approx. Vol of Solvent in ml/gm of Solute

Very soluble less than 1

Sparingly soluble 30 to 100

Slightly soluble 100 to 1000

Very slightly soluble 1000 to 10,000

Practically insoluble more than 10,000

COLD TEMPERATURE 2 to 8 degree centigrade

ROOM TEMPERATURE Prevailing in the working area

WARM TEMPERATURE Between 30 to 40

EXCESSIVE HEAT > 40 degree

SUCROSE BASED DILUANTS

PHARMA-ROCKS AMAR RAVAL 9016312020 EMAIL ID - pharmarocks77@gmail.com 9

% Carr’s Index = (Tapped density – Bulk density) / Tapped density * 100

Hausner’s Ratio = Tapped density / Bulk density H.R = TD / BD

% CI FLOW CHARACTER HAUSNER RATIO