Monophasic Dosage Forms
Monophasic Dosage Forms
Monophasic Dosage Forms
DOSAGE FORMS
Prashant Pandey
M.Pharm. (Pharmaceutics)
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SOLUTION:
“A solution is a liquid-preparation that contains one or
more soluble chemical substances dissolved in a specified
solvent.”
Advantages
Immediately available for absorption
Useful for hygroscopic drugs which must be
administered as a solution
Disadvantages
Less stable Incompatibility is faster
Bacterial contamination
2
Solvents used
A. Aqueous liquids:
Water
Purified Water
Water for injection
Sterile water for injection
Bacteriostatic water for injection
B. Oils &oily materials:
Animals source…pig fat
Vegetable Source…corn,cotton
Mineral Source…liquid paraffin
Synthetics….ethyl oleate
C. Hydroxylated Compounds:
Ethanol
Propylene Glycol
D. Hydro-alcoholic Mixtures
E. Modern Vehicles:
Dioxalanes Solvent for aerosol sprays 3
Dimethylecetamide
-Vehicle for the internal Use
1. Purified Water
2.Aromatic Water
a. Chloroform Water
b. Peppermint Water
c. Cinnamon Water
d. Dill Water
4) Stability
a) Chemical stability 5
b) Physical stability
1.SOLUBILITY
Expression of solubility
According to Indian Pharmacopoeia
Descriptive Phrase - Approximate quantities(ml) of
solvent by volume for 1 part (1 gm) of solute by weight
Very soluble - less than 1 part
Freely soluble - from 1 to 10 parts
Soluble - from 10 to 30 parts
Sparingly soluble - from 30 to 100 parts
Slightly soluble - from 100 to 1000 parts
Very slightly soluble - from 1000 to 10,000 parts
Practically insoluble - more than 10,000 parts
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a. pH
A large number of drugs are either weak acids or weak bases. The
solubility of these agents can be markedly influenced by the pH
of the environment
Weak Acid
pH = pKa + log (ionised ) /(un ionised)
pH = pKa + log (base) / (acid)
Weak Base
pH=pKa +log (unionised) / (ionised)
pH = pKa+ log( base )/(acid)
b. COSOLVENCY
Weak electrolytes and nonpolar molecules frequently
have poor water solubility. These types of solutes are
more soluble in a mixture of solvents than in one solvent
alone. This phenomenon is known as cosolvency.
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c. DIELECTRIC CONSTANT
One property of a solvent system is its dielectric
constant. The dielectric constant of a solvent can
be defined as the ratio of the capacitances of a
capacitor filled with the solvent and air
respectively.
d. SOLUBILIZATION
spontaneous increase of solubility of a poorly water-soluble
solute molecules into an aqueous solution of surface active
agents (or surfactants) in which a thermodynamically stable
solution is formed.
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e. COMPLEXATION
f. HYDROTROPHY
The term hydrotrophy has been used to designate the increase in
solubility in water of various substances due to the presence of
large amounts of additives.
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2.PRESERVATION
a.Preservatives
-Neutral
Chlorbutanol - 0.5
Benzyl alcohol - 1.0
-Mercurial
Thiomersal - 0.001 - 0.1
Nitromersol - 0.001 - 0.1
c. Reducing agent
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3.ORGANOLEPTIC ADDITIVES
a. Colouring Agents
Colouring Agents generally used in case of cosmetic
preparations.
Classification-
Plants:
a. Chlorophyll-green
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Animal:
- Cochineal:
It is an alkaline solution of the soluble Colouring principles
caraminic acid of cochineal insects preserved by the addition of.
It is very dark purplish red liquid.
Minerals:
-Mineral colours are termed pigments.
-They are used to colour lotions, cosmetics and other preparation for
external application.
-As they are toxic, their use for internal preparation is forbidden.
Ex: Red ferric oxide
Yellow Ferric Dioxide
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2. Synthetic colouring agents
The synthetic colours are coal tar dyes, because many of them
are produced from substance obtained from coal-tar.
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Classification of flavouring agents
Two Types:
1. Natural and
2. Synthetic
1. Natural
a. Fruits (Sweet, Sur and Astringent)
Citrus Fruits (Orange, Lemon)
b . Seeds (Vanilla, Anise, Nutmeg)
2.synthetics
Benzaldehyde - Bitter Almond, Cherry pits
Sucrose
Sorbitol (Half Sweet than Sucrose)
Glycerin
Honey
Saccharin Sodium (300-550 times)
Cyclametaes (30 times sweeter than sucrose)
Aspartame
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d.Viscosity control
Used to increase palatability and pourability
Examples of viscosity controlling agents are
-PVP
-cellulose derivatives
e.General apperance
depends on colour and clarity
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4.STABILITY
a. Chemical stability
Ex- effect of amino acids on stability of aspirin in
propylene glycol solutions.
b. Physical stability
Oral liquids are stable if it retains
viscosity,colour,taste and odour throughout its shelf
life
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Liquid dosage forms
External suspensions
Internal
Draughts Liquids for Liquids appiled
Liquids appilied
Drops oral cavities on body cavities
on skin
Gargles Douches
Linctus
Mouthwashes Enemas
Syrups Liniments
Throat paints Ear drops
Elixirs Lotions
Glycerites Nasal drops
mixtures collidions
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Throat spray Inhalants and eye drops
ORAL MONOPHASIC DOSAGE FORM
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A. Draughts
It is simple solution (mixture) which contains a single dose.
Each dose is sent in separate bottle.Total volume is 50 ml.
It is essential to be labelled with storage conditions on
draughts.
It is given very early expiry date (48 hours).
Examples:
1.Ipecacuanha emetic draughts-BPC (Treatment of poison)
2. Paraldehyde draughts- Oxidized to
acetic acid and cause death
Do not use, if the solution is discolored.
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B. Drops:
. For vitamins and antibiotics formulation for pediatric purpose.
. It is not meant for higher dose.
. Drops are dispensed in a bottle with dropper.
. It contains potent drugs, so dose is measured precisely.
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C. Linctuses
Viscous liquid oral preparations that are usually prescribed for
the relief of cough.
Consists of simple solution of active agent in high conc of
sucrose.
Vehicle is always a syrup and sometimes contains glycerin,
because of sweetening taste and soothing effect on mucous
membrane.
Should be taken as such without dilution and sipped slowly to
prolong action of drug
EXAMPLE OF LINCTUSES: -
Codeine Linctuses
Diamorphine Lictus
Compound Tolu Linctus
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FORMULATION OF LINCTUSES
1. Vehicle 2. Additives
1. Vehicles:
a. Syrup
b. Tolu Syrup
It also provides aromatic odour and flavour, it has also mild
expectorant action.
Due to high content (68%) of sucrose, solution tends to
crystallise, so stored at constant temperature.
Due to high solid and low water content, dissolution of
medicament is slow. Sometime glycerol is used as Auxiliary
Vehicle.
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2. Additives
A. Chemical Stabilizers :
Linctuses are self stabilized due to syrup, so no need of
any other stabilizer.
B. Colouring Agent:
Coal-tar dyes
Ex: Compound Tartrazine solution
C. Flavouring Agent:
Syrup itself act as masking agent. Some fruit flavours used
are;
Lemon and Black current
D. Preservatives: Syrup has preservative action due to high
osmotic pressure.
Tolu syrup contain Benzoic acid and cinnamic acid.Some
other preservatives are -Chloroform spirit -Benzoic acid
spirit solution
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D . SYRUPS:
“It is concentrated aqueous solution of sucrose mixed with
solution of medicaments and others additives.”
Generally syrup is prepared by sucrose but is partly replaced
by dextrose or other polyhydric alcohols to reduce
crystallisation of sucrose or to increase solubility of
medicaments and other additives.
Consists of 85% sugars
2 types of syrups
Non medicated syrup
Medicated syrup
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FORMULATION OF SYRUP
Sugar-85%
Anti microbial preservatives(0.1-0.2%)
colorant
Example- Active drug – 5ml
Other drug solids -3ml
Glycerin - 15ml
Sucrose -25g
Ethanol - 95%qs
Purified water - 100ml 29
Function of Syrups
Sweetening agent
Good antioxidant
Preservatives
Demulcents and
soothing agent
EXAMPLES OF SYRUPS:
Codeine phosphate syrup
Squill syrup
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Syrups are used for formulating
Antibiotics
Antitussives
Antihistamines
Vitamins
Analgesic/antipyretic
PREPARATION OF SYRUP –
1.Solution with heat: For non-volatile, thermostable drugs
2.Agitation without heat: For volatile, thermolabile drugs
3.Addition of medicating liquid to syrup: For liquid
medicaments such as extracts, tinctures
4.Percolation: 31
E. ELIXIRS
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ADDITIVES
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Formulation of phenobarbital elixir
phenobarbital - 4g
orange oil - 0.25ml
propylene glycol - 100ml
alcohol - 200ml
sorbitol solution - 600ml
colour - qs
purified water - 1000ml
EXAMPLES-
Chloral Elixir
pediatric Paracetamol Elixir
Ephedrine Elixir
Phenobarbitone Elixir 34
F.MIXTURES
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Liquids for Special Use (Oral Cavity)
Gargles
Mouth-washes
Throat paints
Glycerites
Throat Spray
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A. Gargles:
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B. Mouth Washes
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C. Throat Paints
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D. Glycerites
These are viscous hygroscopic liquids or semisolids
preparations which contain not less than 50% by weight of
glycerin and dissolved medicaments.
Glycerites have sweet taste and does not become rancid. They
also act as preservatives.
Glycerites are hygroscopic and should be preserved in air
tight container.
EXAMPLES:
Borax glycerin - Used as bacteriostatic
Phenol glycerin - Mouth ulcer
Tannic acid glycerin - in ulcer
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E. Throat Spray
Spray solutions are aqueous alcoholic or glycerin solution
intended for throat or nose by means of atomizer or nebulizer.
The spray device should produce coarse droplets for upper
respiratory tract, while fine droplets for lungs (produced by
nebulizer).
Spray solution contain antibiotics, antihistaminic,
vasoconstrictors, alcohol and suitable solubilizing and wetting
agents. Spray solution contain chlorbutol as an antibacterial
and antifungal agent.
EXAMPLES:
Adrenaline and
Atropine spray compound-BPC.
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LIQUIDS FOR SPECIAL USE (OTHER THAN
ORAL CAVITY):
DOUCHES
ENEMAS
EAR-DROPS
NASAL DROPS
INHALANTS/SPRAY/AEROSOLS
Eye drops
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A. Douches
Douches is medicated aqueous solution for rinsing body cavity
applied at lower pressure like
Eye douches
Pharyngeal douches
Nasal douches
Vaginal douches
Bladder douches
Rectum douches
Generally three cavities are widely used ;
For vaginal purpose termed as Douches
For bladder purpose termed as Irrigation
For rectum purpose termed as Enemas.
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-Douches are restricted to vaginal solution have cleansing
or antiseptic action.
-Promote healing or as an astringent.
-Vaginal douches must be sterile if used after child birth
or surgery. -Bladder irrigation must always be sterile
as bladder is a sterile organ. Vaginal douches are
introduced by means of a suitable rubber syringe. have
pH 5.5
-Douches dispensed as concentrated forms and directions
for dilution with warm water.
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Category Ingredients
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1.CLEANSING ENEMAS: Cleansing enemas used to
evacuate feaces in constipation or before an operation.
Two types:
A. By stimulating of peristalsis
i . Large volume: Plain water Soft soap Turpentine
enemas
ii. Small volume (Osmotic retention)
Sodium phosphate enema
Magnesium sulphate enema
Sorbitol Sodium chloride
Sodabicarb
B. By lubricating impacted feaces:
Olive oil enemas
Araches oil Enemas
Glycerin enemas
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2.THERAPEUTICS ENEMAS:
Category Ingredient
a. Sedative Chloral hydrate Paraldehyde
b.Anthelmintics Quassia
c. anti-inflammatory Corticosteroids
d. nutrients
3.Diagnostic enemas:
It is used for X- Ray Examination of lower bowel.
Ex: Barium sulphate enemas.
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4.Disposable Enemas
Enemas available in disposable plastic bags.
They include
evacuant enemas like magnesium sulphate
retention enemas of prednisolone .
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C. Ear Drops:
Ear drops are solutions or suspension of drugs that are
used into the ear. VEHICLES: - Water ,Propylene
glycol,glycerin , PEG-4000 ,Dil. Alcohol ,Haxylene glycol
uses category
1. For mild infection Antibiotics, anti bacterial
2. For softening wax Hydrogen peroxide,
sodabicarb
3. For cleansing Spirit
4. Drying weeping surface Astringent, ammonium
acetate
5. antiseptic- anaesthesic phenol
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CONTAINERS: Coloured fluted glass bottle with
dropper
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D.NASAL DROPS
“Nasal drops are liquid preparation and may be aqueous or oily
for instillation into nostrils.”
The following category can be formulated for nasal drops: -
sympathomimetics ------- vasoconstrictor (ephedrine)
Anti niflammatory ------ corticosteroids
Anti bacterial
Anti histamine
Local anaesthetics
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Nasal Vehicles: they should possess following properties:
- pH range of 5.5-7.5.
- Have mild buffer capacity.
- Tonicity equivalent to normal saline.
- The viscosity should not exceed the normal viscosity of
nasal mucus. Contain antimicrobial agents
Containers : -
Fluted color glass bottle with plastic screw cap and
dropper.
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E. Nasal inhalation
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Label: SHAKE BOTTLE BEFORE USE
Examples:
Benzoin inhalation
Menthol and benzoin inhalation
Menthol and eucalyptus inhalation
Epinephrine inhalation.
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Nasal Sprays
Spray solutions are aqueous alcoholic or glycerin solutions
in the form of coarse droplets of finely divided solids
intended to be applied to the nose or throat by means of
atomizer.
The type of atomizer used depends upon the viscosity of
the spray solution.
Oily solutions were formerly used, but are no longer used
as they retard ciliary action and enter in
trachea and cause lipoidal pneumonia.
Examples:
Anti inflammatory (corticosteroids)
Antihistaminics --Sympathomimetics
Local anaesthetics -- Antimigraine
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F. EYE DROPS
Sterile, aqueous/oily solutions or suspensions intended for
instillation in eye sac.
Eye drops may contain buffers, stabilizing agents, dispersing
agents, solubilizing agents, anti-oxidants & agents required for
tonicity/ viscosity adjustment.
Single dose container should not contain anti-microbial
preservative.
In case of multi dose container a dropper should be supplied
with it for administration.
Maximum size of such containers is 10 ml.
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LIQUIDS FOR EXTERNAL USE
LINIMENTS
LOTIONS
COLLODIONS
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A. LINIMENTS
“Liniments are fluid, semi-fluid or occasionally semisolid
preparations intended for external application.”
They may be alcoholic or oily solution or emulsion.
Liniments containing substances have following
properties.
Analgesic
Rubefacient
Counter Irritants
Soothing
Stimulating
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In case of monophasic (solution) liniments
two types of solvents are used.
1. Alcohol - Soap liniment
- Aconite liniments.
2. Oil - Camphor Liniments
- Methyl Liniments
- Arachis and cotton seed oil is used. It is less irritant than
alcohol. It is spread more easily.
-Liniments may be applied with or without friction. It
may be painted or applied on skin by brush.
- Liniments should not be applied on broken skin.
- Liniments contains volatile ingredients
so cold storage is necessary and kept away from flame
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PREPARATION: It can be prepared as solution or
emulsion as the case may be.
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B. LOTIONS
“Lotion are liquid preparations intended for external
application or for special use.It may be aqueous or alcoholic
solution or suspension referred as SHAKE LOTION.
In aqueous or alcoholic solution, the main ingredients are salts.
Alcohol causes defatting, countered by addition of castor oil.
Sometimes salt dissolved in water- aqueous solution, termed
as EYE-LOTION, meant for eyes.
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-On application of shake lotion on skin, the water
evaporates, leaving residue of medicaments on skin.
- The evaporation causes cooling effect.
-Lotions are applied to inflammed area.
-The use of alcohol hasten (faster) drying and enhance
cooling.
- The use of glycerin keeps skin moist and promote
adherence of residue powder on skin.
- The suspending agent like Na C.M.C. may be used to
assist dispersion.
-Lotion liable to microbial growth, so includes proper
preservatives. Lotion used for local cooling, soothing,
protective, drying or moisturizing properties.
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Lotion includes- antifungal, anti-inflammatory, anti-
infective, anti pyretic and local anesthetic agents.
EXAMPLES:
Lead lotion - lead subacetate in water
Salicylic lotion - salicylic acid in alcohol
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C. COLLODION
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EXAMPLES:
Flexible Collodion –USP/BP
Salicylic acid collodion -BPC
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MANUFACTURING CONSIDERATION
-Raw materials
-equipments
-Cleaning of equipments
-Material of construction
-compounding proceduce
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RAW MATERIALS
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EQUIPMENTS
The following types of equipments may be used in
the manufacture of oral liquid solutions:-
1. Mixing tanks (SS 316 Stainless Steel) equipped
with an agitator.
2. Measuring devices for large and small amount
of solids and liquids.
3. A filtration system for the final polishing - e.g.
Sparkler filter.
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CLEANING OF EQUIPMENTS
72
Material of construction
74
Steps of preparation
1. Purified water is heated to approximately 50 degrees to
facilitate the dissolution of the solid solutes. Solid solutes
are added to the warm water.
2. If any additive is required in small amount then it should
be dissolved separately and then mixed with the bulk
mixture.
3. Any large volume liquids (e.g. glycerol) are added and
mixed until homogeneous.
4. Before adding flavors the temperature should be reduced
to 30degrees(since most of the flavors are volatile). The
flavor should be dissolved in small amount of alcohol (since
flavors are generally insoluble in aqueous medium) and then
it is mixed with the bulk mixture.
5. Dye should be dissolved n small amount of water. Then
transferred to the bulk mixture.
6. Finally volume is made up to the required volume. The
total mixture is agitated thoroughly until homogeneity is
obtained.
7. Finally the batch is filtered to obtain a polished, clear 75
solution
PAKAGING MATERIALS
a. glass
b. plastic
Plastic containers
Glass containers
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FILLING
- gravimentric
- volumentric
- constant level filling
77
Liquid Filling System
78
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CONCLUSION
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REFERENCES
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