College of Pharmacy & Health Sciences

Department of Pharmaceutical Sciences

Laboratory Manual
 

Physical Pharmacy

Supervised by: Dr. Sai HS. Boddu

Lab Instructor: Dr. Sundos Qassim

1
 Table of Contents

Unit Topics Wee Page

k
1 Determination of solubility of some 1-2 3
pharmaceutical solids.
2 Determination of CMC of surfactants. 3 7

3 Solubilization of hydrophobic drugs using 4-5 10

surfactants.
4 Measurement of viscosity of some pharmaceutical 6 12
solvents using the U-Tube viscometer.
5 Stability of colloids. 7-8 15

6 Determination of sedimentation rate & 9-10 17

sedimentation volume of a sulphonamide
suspension.
7 Tutorial covering semisolids: Criteria of 11-12- 19
choosing, Pharmaceutics case study, clinical case 13
study and pharmaceutical care plan.
8 Tutorial illustrating pros & cons of liquids 14 32
aerosols vs. dry powders for inhalation.
Proper use of inhalers.
9 Tutorial covering physicochemical drug 15 37
interactions and incompatibilities.
10 Final exam. 16 -

2
1. Determination of Solubility of Some
Pharmaceutical Solids
A solution may be defined as a mixture of two or more components that form a
single phase (homogeneous). The component that determines the phase of the
solution is termed the solvent; it usually (but not necessarily) constitutes the
largest proportion of the system. The other component(s) are termed solute(s)
and these are dispersed as molecules or ions throughout the solvent, i.e. they are
said to be dissolved in the solvent. The transfer of molecules or ions from a
solid state into solution is known as dissolution.1

The solubility of a substance is the amount of it that passes into solution when
equilibrium is established between the solute in solution and the excess
(undissolved) substance. The solution that is obtained under these conditions is
said to be saturated. A solution with a concentration less than that at equilibrium
is said to be subsaturated. Solutions with a concentration greater than
equilibrium can be obtained. These are known as supersaturated solutions. Since
the above definitions are general ones, they may be applied to all types of
solution involving any of the three states of matter (gas, liquid, solid) dissolved
in any of the three states of matter, i.e. solid-in-liquid, liquid-in- solid, solid-in-
vapour, vapour-in-liquid, etc. However, when the two components forming a
solution are either both gases or both liquids then it is more usual to talk in
terms of miscibility rather than solubility. Otherwise all principles are the same.
One point to emphasize at this stage is that the rate of solution (dissolution rate)
and amount which can be dissolved (solubility) are not the same and are not
necessarily related. In practice, high drug solubility is usually associated with a
high dissolution rate, but there are exceptions; an example is the commonly
used film coating material hydroxypropyl methylcelluose (HPMC) which is
very water soluble yet takes many hours to hydrate and dissolve.2

Importance of solubility:
 Therapeutic effectiveness of a drug depends upon the bioavailability
and ultimately upon the solubility of drug molecule.
 Solubility is one of the important parameter to achieve desired
cconcentration of drug in systemic circulation for pharmacological
response to be shown.

1
Aulton E.M. Aulton`s Pharmaceutics The design and Manufacture of Medicines, 3rd Edition, Elsevier. 2007.
2
Aulton E.M. Aulton`s Pharmaceutics The design and Manufacture of Medicines, 3rd Edition, Elsevier. 2007.

3
  Currently only 8% of new drug candidates have both high solubility
and Permeability.
 Nearly 40% of the new chemical entities currently being discovered
are poorly water soluble. 3

Practical: Determination of Solubility of Drugs in Single and Mixed Solvents

The solubility of a substance fundamentally depends on the solvent used as well

as on temperature and pressure. The extent of solubility of a substance in a
specific solvent is measured as the saturation concentration where adding more
solute does not increase its concentration in the solution4
So, the amount of drug present in a saturated solution at a particular temperature
is called solubility. (E.g. The solubility of paracetamol is 1 g in 70 ml water at
20 0C). The solubility of a drug is determined by preparing a saturated solution
of the drug. A saturated solution is prepared by shaking excess quantity of the
drug with the solvent for a long time (48 hours). This system is filtered and the
saturated solution is analyzed for drug content by titration or suitable analytic
method.
In this experiment, solubility of salicylic acid is found out in water and 10 %
alcohol. The amount of salicylic acid dissolved in the solvent is analyzed by
titrating with 0.025 N NaOH solution using phenolphthalein as indicator. When
a drug has poor solubility in water, alcohol can be used as a co-solvent to
prepare solutions. In the present experiment the solubility of salicylic acid is
improved using alcohol as a co solvent.

Aim: To determine the solubility of salicylic acid in water and 10% alcohol
Materials Required: Apparatus Required:
Salicylic acid Measuring cylinder
distilled water Funnel
10 % alcohol Beaker
0.025 N NaOH conical flask
phenolphthalein indicator 10 ml bulb pipette
filter paper rubber bulb
burette
burette stand
Procedure:

3
https://www.slideshare.net/Drzulcaifahmad/solubility-method-for-determination-of-solubility
4
Lachman L, Lieberman H, Kanig JL. The Theory and Practise of Industrial Pharmacy. 3rd edition. Lea & Febiger;
1986.

4
 For aqueous solution of salicylic For hydro-alcoholic solution of
acid salicylic acid

1. Take 50 ml of distilled water in a 1. Take 50 ml of distilled water or

clean dry conical flask, add a 5g 10% alcohol in a clean dry
of salicylic acid and shake conical flask, add 5g of salicylic
vigorously for 30 minutes. If the acid and shake vigorously for 30
added salicylic acid has minutes. If the added salicylic
dissolved, add another 5g of acid has dissolved, add another
salicylic acid and continue 5g of salicylic acid and continue
shaking to obtain a saturated shaking to obtain a saturated
solution. (count how many grams solution. (count how many grams
did you take) did you take)
2. Filter the contents into a clean 2. Filter the contents into a clean dry
dry beaker. beaker.
3. Titrate 10 ml of the filtrate with 3. Titrate 10 ml of the filtrate with
0.025 N sodium hydroxide 0.025 N sodium hydroxide
solution twice using solution twice using
phenolphthalein as indicator phenolphthalein as indicator.
(discard the chemical from the (discard the chemical from the
flask and rinse it with distilled flask and rinse it with distilled
water after titrating each 10 ml) water after titrating each 10 ml)
4. Calculate the solubility of 4. Calculate the solubility of
salicylic acid in water. salicylic acid in hydro alcoholic
solvent.
Observation and Calculations
Initial Final Titre. Initial Final Titre.
No Solution in burette burette value No Solution in burette burette Value
. Conical reading reading (Final- . Conical reading reading (Final-
flask Initial) flask Initial)
1 10 ml aqueous 1 10 ml hydro
solution alcoholic
solution
2 10 ml hydro
2 10 ml aqueous
alcoholic
solution
solution

Calculation of solubility of salicylic

acid in water: Calculation of solubility of salicylic
acid in 10% alcohol:

5
Salicylic acid solubility in mg/10 ml
= Salicylic acid solubility in mg/10 ml
Titre value x I.P factor* =
Titre value x I.P factor*
Salicylic acid solubility in mg/100 ml
= Salicylic acid solubility in mg/100 ml
Titre value x I.P factor* x 10 =
Titre value x I.P factor* x 10
*I.P factor: Each ml of 0.025 N
NaOH is equivalent to 3.45 mg of *I.P factor: Each ml of 0.025 N
salicylic acid. NaOH is equivalent to 3.45 mg of
salicylic acid.

Result

The solubility of salicylic acid in The solubility of salicylic acid in 10%

water is _______ mg/100ml. alcohol is _______ mg/100ml.

6
2. Determination of the Critical Micellar
Concentration of a Surfactant
Sodium Lauryl Sulphate is a surfactant. It has a
hydrophilic head and a lipophilic tail. At low
concentrations, SLS molecules occupy the surface of
water and reduces the surface tension. As concentration
of SLS increases, the surface tension of water
decreases. At a particular concentration there is no place for the SLS molecules
at the surface. Now the SLS molecules go into the bulk of the water and form
spherical aggregates called micelles. The concentration at which micelles start
forming is called critical micelle concentration or CMC. Above CMC the
surface tension of water does not decrease any further.
At CMC the properties of surfactant solutions
like surface tension, interfacial tension, osmotic
pressure, electrical conductivity, etc. change
sharply. By detecting the sharp change in one of
these properties with concentration of SLS, we
can predict the CMC. In the present experiment
the CMC of SLS is determined by surface
tension method. 5

Practical:

Florence, A. T. and Attwood, D., Physical Pharmacy, Pharmaceutical Press, London, 182 p.
5

7
 Determination of the Critical Micelle Concentration of a Surfactant

Aim: Application of surface tension measurements for determination of

critical micelle concentration (CMC).
Materials Required: Apparatus Required:
SLS, distilled water Stalagmometer, burette stand, one big
beaker, one small beaker, 10 ml
graduated pipette, 50 ml measuring
cylinder, stop watch, rubber bulb, and
wash bottle
Procedure and Calculations:
1.Prepare the following concentrations of sodium lauryl sulfate (SLS) using
the stock solution provided (1%): 0.02, 0.04, 0.08, 0.1, 0.2, and 0.3%
C1V1 = C2V2
Sample Stock
Concentratio Calculation V2 Procedure
n
0.02% SLS   V2=  
 
0.04% SLS V2=  
   
0.08% SLS V2=  
   
0.1% SLS V2=
 
0.2% SLS V2=
 
0.3% SLS V2=
 
2. Determine the surface tension of the above prepared solutions by drop
number method. Use the Stalagmometer to count the number of drops in a
specific volume of each solution using water as a standard for determination
of surface tension.
 Fix a clean, dry stalagmometer vertically to a burette stand.
 Dip the stalagmometer in a beaker containing water and suck water
into stalagmometer using a rubber bulb above mark A.
 Now allow the water to flow down.

8
  Start counting drops when water meniscus crosses the mark A, and
continue counting until the water meniscus crosses mark B.
 Repeat the steps.
 Calculate the surface tension of surfactant solution using the below

Result Plot a graph by taking concentration of SLS on x-axis and surface

tension of SLS solutions on y-axis. From the graph find out the CMC
(the concentration of surfactant solution after which no more
reduction of surface tension)

Graph Paper

9
3. Solubilization of Hydrophobic Drugs
using Surfactants

Solubility is defined as the maximum concentration that the solute can

achieve in a given volume of solvent at a certain temperature. There are
several factors that can affect the solubility of a compound such as the
physical and chemical properties of the solute (polarity, molecular
size...etc.), temperature, pressure, and the pH of the solution.
There are different ways to increase the solubility of hydrophobic drugs.
(e.g. Co-solvency, Salt Formation, Solubilisation by complexation, micellar
solubilisation i.e. Using a surfactant.)
Surface-active agents (surfactants) form micelles in aqueous solution above a
critical concentration called the critical micelle concentration (CMC). In
aqueous solution, the micelle has a hydrophobic core and a dielectric gradient
towards the surface of the micelle making the micellar surface hydrophilic.
Thus, the micelle can act as a soluble phase for non-polar solutes (core), semi-
polar solutes (palisade layers) and polar solutes (surface). As a result, the
efficiency of a particular surfactant as a solubilizing agent varies from substance
to substance. The process of increasing the water solubility of a solute (drug)
using a surfactant is called micellar solubilization. This process is illustrated in
the following figure.

10
Practical:

Aim: To increase the solubility of salicylic acid using a surfactant

Materials Required: Apparatus Required:
Salicylic acid Conical flask
Tween 80 Burette
Distilled water graduated cylinder
Weighing balance
spatula
Procedure and Calculations:
1. Put 1 g of salicylic acid in a conical flask.
2. Add 10 mL of distilled water to the flask and shake it to observe the
solubility of salicylic acid.
3. Add Tween 80 from a burette drop by drop with continuous shaking
until all crystals of salicylic acid dissolve. Measure the amount of
surfactant used and Calculate its percentage in the final mixture.

Result Express the solubility, Solubility is often expressed in grams of

solute per 100 g of solvent (Water + Surfactant)

11
4. Measurement of Viscosity using the
Ostwald Viscometer
Viscosity (ƞ) is the resistance of a fluid to flow. A fluid with high viscosity
flows slowly while a fluid with low viscosity flows quickly. Units of
Viscosity is
Poise (1 Poise = 100 centipoise (cps))
Viscosity can be measured using Ostwald Viscometer
(Capillary-type viscometer) which is U-shaped glass
apparatus with a wide arm and a narrow one with a
capillary tube in the narrow part. There are two marks (C
& D); above and below the bulb in the narrow part. In
this method the viscosity of a liquid (ƞ1) can be
determined in relation to another liquid of known
viscosity (ƞ 2).
The viscosity of the liquid under test (ƞ1) can be found by
measuring the time (t 1) required for this liquid to pass
between the two marks (C & D) as it flows by gravity
through the vertical capillary tube. This time is compared
with the time (t 2) required for a liquid of known viscosity
(ƞ2) [usually water] to pass between the two marks. If the
two liquids have the same or close densities, they can be neglected.

ƞ1 t 1
=
ƞ2 t 2

If the two liquids have different densities, then:

Where, ρ is the density, t is the time of outflow of the sample, ρ0 is the density,
t0 is the time of the outflow of the reference liquid (water). Knowing η0 the
viscosity of the sample can be calculated. We have to measure the density of the
sample.
Practical:

12
Aim: To determine the viscosity of a sample using Ostwald Viscometer
Materials Required: Apparatus Required:
Ethanol Ostwald viscometer
Distilled water Pipette
Pump
Weighing balance
cylinder
Procedure and Calculations:
1. Clean and dry the viscometer.
2. Fill the viscometer with your sample through point A
Until the liquid reaches point E. Suck through arm B to
make our sample move to C. Measure the time needed for
the sample to move from C to D. Repeat for three times
and take the average.

Sample t1 t2 t3 taverage
Water        

Ethanol

 Measure the density of the sample by placing an empty cylinder over the
weighing balance then press Zero then add 10 mL of the sample to the
measuring cylinder then take the weight and calculate density as shown
below.

13
Result

5. Stability of Colloid
A colloid is a mixture in which one substance of microscopically dispersed
insoluble particles are suspended throughout another substance. Sometimes the
14
dispersed substance alone is called the colloid. The colloid consists of a dispersed
phase and a continuous phase. Unlike solutions, colloids do not constitute a solute
dissolved in the solvent phase. Rather, the solute phase is dispersed in the solvent
phase. Types of Colloids include:

 Sol – It is a suspension of minute solid particles in a liquid.

 Emulsion – It is a colloid between two or more liquid with one consisting
a dispersion of another liquid.
 Foam – It consists of gas dispersed in solid or liquid.
 Aerosol – It consists of a minute liquid or solid particles in a gas.

The colloid is said to be stable

when particles remain suspended
in the solution without settling
down i.e. the dispersed phase.
Stability is hindered by
aggregation and sedimentation
phenomena, which are driven by
the colloid’s tendency to reduce
surface energy. In order to
stabilize the colloidal system, we need to reduce the interfacial tension between
the colloidal particles.

Aggregation is due to the sum of the interaction forces between particles. If

attractive forces (such as van der Waals forces) prevail over the repulsive ones
(such as the electrostatic ones) particles aggregate in clusters. Electrostatic
stabilization and steric stabilization are the two main mechanisms for stabilization
against aggregation.

Colloids can be broadly classified as: lyophobic (hydrophobic in aqueous

systems), lyophilic (hydrophilic in aqueous systems).6

Practical:
Aim: To illustrate the effect of electrolytes on hydrophilic and hydrophobic
colloids exemplified by gelatin and hydrated Ferric oxide solutions.
Materials Required: Apparatus Required:
Na2SO4 ,distilled water, gelatin, Fe2O2 Pipette, Pump, Measuring cylinder
Procedure and Calculations:
Prepare 10 ml of different conc. of Na2SO4 (0.02%, 0.06%, 0.08%, 0.1%,

6
Florence, A. T. and Attwood, D., Physical Pharmacy, Pharmaceutical Press, London, 182 p.

15
 0.6%, and 1%) from 2% Na2SO4 using the following equation :
C1V1 = C2V2
Sample Stock
Concentration Calculation V2 Procedure
0.02% Na2SO4   V 2=  
0.06% Na2SO4   V 2=  
0.08% Na2SO4   V 2=  
0.1%   V 2=  
Na2SO4  
0.6%   V 2=  
Na2SO4
1%   V 2=
Na2SO4
Bring 12 test tubes, 6 for gelatin and 6 for Fe2O2 and add for each 2ml of the
corresponding colloids then add to each 1ml of Na2SO4

Wait for 10 min and observe the result whether stable or not stable (observe
the occurrence of any turbidity)
Result Determine the conc. of electrolyte used for causing precipitation of
colloidal particles.

6. Determination of sedimentation rate

of Magnesium Hydroxide
Stoke’s Law (sedimentation Rate) describes a relationship between the settling
rate of particles in a liquid to particle size, their respective densities, and the
viscosity of the liquid. Inherently, larger/heavier particles will fall out of

16
suspension faster. Settling rate will also depend on the relative density of the
particles and the fluid they are suspended in. For instance, if the particles are
less dense than the fluid, they will rise instead of fall. Stoke’s law is expressed
using the following mathematical relationship:

18 n 2 . v
d=√
( ρs− ρo ) g

• V is the particles' settling velocity (cm/s)

• d is the diameter of the particle
• g is the gravitational constant (980 cm/s2)
• ρs is the density of the particles (g/cm3)
• ρo is the density of the liquid (water) (g/cm3)
• η is the dynamic viscosity of the particles (c.p)

Practical:

Aim: Determination of sedimentation rate of calamine powder and find out

the velocity and diameter of calamine particles
Materials Required: Apparatus Required:
Calamine powder, distilled water Pipette, Pump, Weighing
Balance, Measuring cylinder
Procedure and Calculations:
1. Measure 5g of calamine powder and disperse it in 15 ml of water.
2. Make up the volume to 25mL with water.
3. Mix well and then adjust the volume.
4. Measure the height of sediment layer (pink layer) at time mentioned
below
Time 0 5 10 15 20 25 30
(minutes)
Height
(centimetres)
5. Plot time vs. height and find out the slope.

17
 Graph Paper

6. Calculate the diameter of calamine particle using the equation below:

18 n 2 . v
d=√
( ρs− ρo ) g

Resul
t

7. Tutorial covering semisolids: Criteria

of choosing, Pharmaceutics case study,
Clinical case study and Pharmaceutical
care plan.
Topical medications introduce medication through the skin, by absorption.
Topical medications come in many forms: ointments, lotions, pastes, creams,

18
powders, sprays, and shampoos.7 There are many advantages and disadvantages
of topical formulations. These include:8

Advantages Disadvantages
 An increased dose of medication  They can be time-consuming to
is applied where it is needed apply
 There are reduced side effects  At times, the regimen can be
and toxicity to other organs complicated, especially if several
compared different formulations have been
to systemic medications. prescribed
 The applications may also be
messy or uncomfortable.

Types of Topical Formulations: 9 10 11

 Ointments: semi-solid preparations of hydrocarbons (petrolatum, mineral oil,

paraffins, synthetic hydrocarbons)

- strong emollient effect makes it useful in dry skin conditions

- occlusive effect enhances penetration of active drug and improves
efficacy (especially in thickened, lichenified skin)
- provides a protective film on the skin (e.g., useful in housewife’s hands,
irritant dermatitis)
- greasy, sticky, retains sweat (therefore, not suitable in wet weepy
dermatitis, hairy areas, skin prone to folliculitis, or hot weather
conditions)
- contains no water and does not require a preservative so they are less
likely to cause an allergic reaction (better to use on sensitive skin)
- Ointments are best when treating dry skin conditions, such as psoriasis.
Because they trap moisture and are not well absorbed into the skin. Thus,
they are able to keep the skin moist for longer periods of time.
- Ointments allow greater penetration of the active ingredient in the topical
medication, whether it is an antibiotic, steroid, or anti-fungal medication.
- The best moisturizers are in ointment form.

7
Delegation of Medication Administration to Unlicensed Assistive Personnel (UAP), NC Board of Nursing.
Retrieved from https://www.ncbon.com/vdownloads/medication-administration-teaching-modules/module-
topical-medication.pdf
8
Aulton, M. E. and Taylor, K. M. G., Aulton's Pharmaceutics The Design and Manufacture of Medicines,
London.
9
Delegation of Medication Administration to Unlicensed Assistive Personnel (UAP), NC Board of Nursing.
Retrieved from https://www.ncbon.com/vdownloads/medication-administration-teaching-modules/module-
topical-medication.pdf
10
http://www.dermweb.com/therapy/common.htm
11
https://www.edocamerica.com/health-tips/creams-and-ointments-whats-the-difference-which-is-best/

19
 Creams:

- emulsion of water and oil

- classified as oil in water (o/w) or water in oil (w/o) emulsions
- o/w creams (e.g. vanishing creams) spread easily and do not leave the
skin greasy and sticky
- w/o creams (e.g. cold cream) are more greasy and more emollient
- creams contain emulsifiers and preservatives which may cause contact
allergy
- Creams may work better on larger areas of the skin because of their
"spreadability" factor, compared to ointments. 
- Wet or “weeping” skin lesions, such as eczema or poison ivy, are best
treated with a cream (or gel).

 Gel

- transparent preparations containing cellulose ethers or carbromer in water

or a water-alcohol mixture
- gels liquify on contact with the skin, dry and leave a thin film of active
medication
- gels tend to be drying
- they are useful in hairy areas
- they are cosmetically acceptable

 Lotions:

- an o/w emulsion with a high water content to give the preparation a liquid
consistency can be considered a lotion
- most lotions are aqueous or hydroalcoholic systems; small amounts of
alcohol are added to aid solubilization of the active ingredient(s) and to
hasten evaporation of the solvent from the skin surface
- most acne lotions are hydroalcoholic which evaporate fast; they are non-
sticky and drying
- emulsion type lotions are usually not drying, depending on the water
content (higher water and/or less oil is more drying)
- lotions are easy to apply to large areas
- lotions are suitable for hairy areas, skin prone to folliculitis/acne,
intertriginous areas

 Pastes:

20
 - mixture of powder and ointment (e.g., zinc oxide 20% paste)
- addition of powder improves porosity (breathability). For example, when
treating diaper rash, a protective ointment base which also allows
breathability of the skin is desired.

- addition of powder to change an ointment into a paste also increases the

consistency of the preparation so that it is more difficult to rub off. This
property is useful when one does not want an irritating preparation to get
onto the normal skin (e.g., anthralin paste for treating psoriasis).

 Powders are very finely ground medications that are usually sprinkled
onto the affected area.

 Sprays are medications in a solution that can be atomized into a mist for
ease of application.

 Shampoos are medications in a soap solution made for application to the

scalp and hair.

Factors to consider when choosing a topical preparation:

General Rules:
-Always consider the effect of the vehicle. An occlusive vehicle enhances
penetration of the active ingredient and improves efficacy. The vehicle itself
may have a cooling, drying, emollient, or protective action. It can also cause
side effects by being excessively drying or occlusive.
-Match the type of preparation with the type of lesions. For example, avoid
greasy ointments for acute weepy dermatitis.
-Match the type of preparation with the site (e.g., gel or lotion for hairy areas).
-Consider irritation or sensitization potential. Generally, ointments and w/o
creams are less irritating, while gels are irritating. Ointments do not contain
preservatives or emulsifiers if allergy to these agents is a concern.

1. Nature of the skin

 Thin skin absorbs more than thick skin — skin thickness varies with body
site, age and the specific skin disorder
 Skin barrier function — this may be disrupted
by dermatitis, ichthyosis and keratolytic agents (such as salicylic acid), so
it may absorb more medication than intact, normal skin

21
  The absorption of the active ingredient is greater where there is occlusion,
such as in the skin folds, under dressings, or when a
greasy, ointment formulation is used. Plastic film or transparent dressing
may be used to cover some topical medications, i.e., cortisone ointment to
increase absorption and protect clothing. Plastic film is not to be used
with all topical medications. Follow manufacturer’s recommendations.
 For wet or oozy skin conditions — creams, lotions, and drying pastes are
most suitable.
 For dry, scaly skin conditions — ointments and oils are appropriate.
 For inflamed skin — use wet compresses and soaks followed by creams
or ointments.
 Cracks and sores — treat with bland applications; avoid alcohol and
acidic preparations.

2. The site of the skin problem

 Palms and soles — an ointment or cream may be preferred.

 Skin folds — use a cream or a lotion (ointments are too occlusive for
these sites)
 Hairy areas — a lotion, solution, gel, or foam is usually best.
 Mucosal surfaces — take care to prescribe non-irritating formulations to
avoid irritating eroded surfaces.

3. The physiochemical properties of the topical formulation used:

 Small molecules are more easily absorbed through the skin than large
molecules
 Lipophilic compounds are better absorbed than hydrophilic compounds
 Higher concentrations of the active ingredient may penetrate more than
lower concentrations
 Other ingredients in the formulation may interact to increase or reduce
potency or absorption rates.
 The potency of a given topical medication may change depending on
whether it is in cream or ointment form. Corticosteroids for example:
Being occlusive, an ointment will allow the medication to enter the skin
more completely than a cream. At the same dosage, most topical
corticosteroids will be classified as being stronger when packaged as an
ointment as compared to a cream.12

12
https://www.dermnetnz.org/topics/topical-formulations/

22
  Moisturizer Ointments, with their higher viscosity, are generally the best
moisturizers. They form a barrier that helps to seal moisture into the skin.
Examples of ointment-based moisturizers include Vaseline. If a less
greasy preparation is desired, cream-based moisturizers that come in a tub
or tube are usually better than lotions.13
Administration of Topical Preparation14 15

1. Check the Label of the medication (name, dose, route, site and expiry
date)
2. Perform hand hygiene and Cleanse hands before and after using the
medication. It`s preferred to apply non-sterile gloves unless skin is
broken; then apply sterile gloves.

3. Wash, rinse, and dry the affected area with water and a clean cloth to
remove previous topical medications. Always clean the skin or wound
before applying a new dose of topical medication

4. After opening the container, place the lid with inside up to keep from
contaminating the inside of the lid. Do not touch the inside of the
container. When finished getting the required amount of medication,
replace and tighten the cap on container.

5. Use gauze or a cotton tipped applicator to apply cream or ointment. If you

get too much out of the container, do not put it back in the container
because of risk of contaminating the remaining medication. Use a new
gauze or cotton tipped applicator EACH time medication is removed
from the container to prevent contaminating the medication left in the
container. Throw away supplies (such as gauze or cotton-tipped swabs)
used in application.
6. Place required amount of medication in palm of
hands and soften by rubbing palms together.
Softening makes topical medication easier to spread
and warmer. Do not administer the cream straight
onto the patient’s skin from the fridge due to its

13
https://www.dermnetnz.org/topics/topical-formulations/

14
https://www.dermnetnz.org/topics/topical-formulations/

https://www.vnhcsb.org/media/data/papers/pdf/340_16.29.3.pdf
15
Doyle, G.R., McCutcheon, J.A. (2015). Clinical Procedures for Safer Patient Care. Victoria,
BC: BCcampus. Retrieved from https://opentextbc.ca/clinicalskills/

23
 temperature. Allow the cream to warm up in the staff member’s gloved
hand for a few moments before applying.16
7. Apply medication using long even strokes that follow the direction of the
hair to avoid irritation of hair follicles. Do not rub vigorously.
8. Obtain a body-lotion applicator to apply the product to an area that's hard
to reach, particularly the back.

General Advices:

 Topical steroids and emollients are more effective if the skin is slightly

wet. So the most effective time to apply them is within 3 minutes after a
bath or shower. Apply the steroid to active areas only. If you are also
prescribed emollient, wait a few minutes for the topical steroid to
penetrate, then apply emollient widely.
 Some emollients contain white soft paraffin or liquid paraffin and these
can sometimes soak into outer clothing after administration. Because
paraffin is flammable, patient need to be made aware of the risk of fire
and should be kept far away from naked flames, ignited cigarettes or open
fires after the use of such preparations.
 The amount of topical steroid that you should
apply is commonly stated as “apply thinly” and
can be measured by 'fingertip units' (FTUs). A
FTU is the amount of topical corticosteroid
needed to squeeze a line from the tip of an adult
finger to the first crease of the finger. The recommended dosage in terms
of FTUs will depend on what part of the body is being treated. This is
because the skin is thinner in certain parts of the body and more sensitive
to the effects of corticosteroids. Corticosteroid creams and ointment need
to be applied thinly because this minimises the amount absorbed into the
body through the skin as corticosteroids are potent compounds and
usually a small amount is needed to achieve the desired effect.17
 Some patients may be prescribed a rub to treat conditions like arthritis.
Such preparations usually contain irritant compounds such as camphor,
salicylic acid, anti-inflammatory compounds or capsicum. (ibuprofen gel,
piroxicam gel, Zacin® cream). It is important to remember to use
16
Bilal, S., 2012, Good Practice Guidance 6: Administration of Creams & Ointments in Care Home, Berkshire
East. Retrieved from: https://www.eastberkshireccg.nhs.uk/wp-content/uploads/2018/03/Good-Practice-
Guidance-6.-administration-of-creams-and-ointments-in-CH-.pdf
17
Bilal, S., 2012, Good Practice Guidance 6: Administration of Creams & Ointments in Care Home, Berkshire
East.
Retrieved from: https://www.eastberkshireccg.nhs.uk/wp-content/uploads/2018/03/Good-Practice-Guidance-6.-
administration-of-creams-and-ointments-in-CH-.pdf

24
 disposable gloves and to wash hands immediately after administering
such preparations. Such preparations should not be applied to inflamed or
broken skin and patient should be made aware of any special precautions
such as not to touch area treated and then to touch eyes or nose e.g. with
Zacin® Cream.18
 Stinging is common with lotions and creams and sometimes also occurs
with ointments, especially if the skin is damp at the time of application.
A change of formulation rather than medicament may solve the problem.
Zngfdsa QERTYUIOP[]21``1234567890-= .

Pharmaceutics case study, clinical case study and pharmaceutical care plan
Eczema/dermatitis19

Eczema is a term used synonymously with dermatitis. The rash of eczema

typically presents as dry flaky skin that may be inflamed and have small red
spots. The skin may be cracked and weepy and sometimes becomes thickened.
The rash is irritating and can be extremely itchy. Many cases of mild-to-
moderate eczema can be managed by the patient with support from the
pharmacist.
What you need to know
Age
Distribution of rash
Occupation/contact
Medical History of hay fever/asthma
Medication History
Aggravating factors
Medication

-Age/distribution
The distribution of the rash tends to vary with age.

-Occupation/contact
Contact dermatitis may be caused by substances that irritate the skin. Irritant
contact dermatitis is most commonly caused by prolonged exposure to water
(wet work). Typical occupations include cleaning, hairdressing, food
processing, fishing and metal engineering. Substances that can irritate the skin
include alkaline cleansing agents, degreasing agents, solvents and oils. Such
18
Bilal, S., 2012, Good Practice Guidance 6: Administration of Creams & Ointments in Care Home, Berkshire
East.
Retrieved from: https://www.eastberkshireccg.nhs.uk/wp-content/uploads/2018/03/Good-Practice-Guidance-6.-
administration-of-creams-and-ointments-in-CH-.pdf
19
Blenkinsopp, A., Paxton, P. and Blenkinsopp, J., Symptoms in the Pharmacy A Guide to the Management of
Common Illness sixth edition, Willey-Blackwell

25
substances either cause direct and rapid damage to the skin or, in the case of
weaker irritants, exert their irritant effect after continued exposure.
In other cases, the contact dermatitis is caused by an allergic response to
substances which include chromates (present in cement and
rust-preventive paint), nickel (present in costume jewellery and as plating on
scissors), rubber and resins (two-part glues and the resin colophony in adhesive
plasters), dyes, certain plants (e.g. primula), oxidizing and reducing agents (as
used by hairdressers when perming hair) and medications (including topical
corticosteroids, lanolin, neomycin and cetyl stearyl alcohol). Eye make-up can
also cause allergic contact dermatitis.
Clues as to whether or not a contact problem is present can be gleaned from
knowledge of site of rash, details of job and hobbies, onset of rash and agents
handled and improvement of rash when away from work or on holiday.

-Aggravating factors
Atopic eczema may be worsened during the hay-fever season and by house dust
or animal danders. Factors that dry the skin such as soaps or detergents and cold
wind can aggravate the condition. Certain clothing such as woollen material can
irritate the skin. In a small minority of sufferers (less than 5%), cow’s milk,
eggs and food colouring (tartrazine) have been implicated. Emotional factors,
stress and worry can sometimes exacerbate eczema. Antiseptic solutions applied
directly to the skin or added to the bathwater can irritate the skin.

-Medical History of hay fever/asthma

Many eczema sufferers have associated hay fever and/or asthma. There is often
a family history (in about 80% of cases) of eczema, hay fever or asthma.
Eczema occurring in such situations is called atopic eczema. The pharmacist
can enquire about the family history of these conditions.

-Medication History
The pharmacist should ask which treatments have already been used. Topically
applied local anaesthetics, antihistamines, antibiotics and antiseptics can all
provoke allergic dermatitis. Some preservatives may cause sensitization. If the
patient has used a preparation, which the pharmacist considers appropriate for
the condition, correctly but there has been no improvement or the condition has
worsened, the patient should see the doctor.

-When to refer
Evidence of infection (weeping, crusting, spreading)
Severe condition: badly fissured/cracked skin, bleeding
Failed medication
No identifiable cause (unless previously diagnosed as eczema)
Duration of longer than 2 weeks
26
-Treatment timescale
Most cases of mild-to-moderate atopic eczema, irritant and allergic dermatitis
should respond to skin care and treatment with OTC products.
If no improvement has been noted after 1 week, referral to the doctor is
advisable.

 Emollients:
Emollients are the key to managing eczema and are medically inert creams and
ointments which can be used to soothe the skin, reduce irritation, prevent the
skin from drying, act as a protective layer and be used as a soap substitute. They
may be applied directly to the skin or added to the bathwater.
There are many different types of emollient preparations that vary in their
degree of greasiness. The greasy preparations such as white soft paraffin are
often the most effective, especially with very dry skin, but have the
disadvantage of being messy and unpleasant to use. Patient preference is very
important and plays a major part in compliance with emollient treatments.
Patients will understandably not use a preparation they find unacceptable.
Patients may need to try several different emollients before they find one that
suits them, and they may need to have several different products (e.g. for use as
a moisturizer, for use in the bath and for use as a soap substitute when washing
or showering).
Emollient preparations should be used as often as needed to keep the skin
hydrated and moist. Several and frequent applications each day may be required
to achieve this.
Standard soaps have a drying effect on the skin and can make eczema worse.
Aqueous cream can be used as a soap substitute. It should be applied to dry skin
and rinsed off with water. Proprietary skin washes are also available. Adding
emulsifying ointment or a proprietary bath oil to the bath is helpful.
Emulsifying ointment should first be mixed with water before being added to
the bath to ensure distribution in the bathwater.
Some patients with eczema believe, incorrectly, that bathing will make their
eczema worse. This is not the case, provided appropriate emollient products are
used and standard soaps and perfumed bath products are avoided, and in fact,
bathing to remove skin debris and rusts is beneficial.

 Topical corticosteroids
Hydrocortisone cream and ointment and clobetasone 0.05% can be sold OTC
for a limited range of indications. OTC hydrocortisone is contraindicated where
the skin is infected (e.g. athlete’s foot or cold sores, in acne, on the face and
anogenital areas). Children aged over 10 years and adults can be treated, and
any course must not be longer than 1 week.

27
  Antipruritics
Antipruritic preparations are sometimes useful, although evidence of
effectiveness is lacking. The itch of eczema is not histamine related, so the use
of antihistamines other than that of sedation at night is not indicated. Calamine
can be used in cream or lotion.

Case 1
Ray Timpson is a local man in his mid-thirties and a regular customer.
Today, he wants to buy some hydrocortisone cream for his eczema, which has
worsened. He has had eczema for many years and usually obtains his
hydrocortisone cream on a repeat prescription from his doctor. As a child, Mr
Timpson was asthmatic and both asthma and hay fever are present in some
members of his family. He has just seen an advert for a proprietary OTC
hydrocortisone cream and says he would prefer to buy his supplies from you in
the future to save both himself and the doctor some time. The eczema affects his
ankles, shins and hands; the skin on his hands is cracked and weeping.

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28
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Case 2
Romiz Miah, a young adult, The skin is flaky but not broken and there is no
sign of secondary infection such as weeping or pus. He says the problem is
spreading and now affecting his arms as well. He has occasionally had the
problem before but not as severely. On further questioning, you discover that he
has recently started working in his family’s restaurant and has been doing a lot
of washing up and cleaning.

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29
30
7. Tutorial illustrating pros & cons of
liquids aerosols vs. dry powders for
inhalation. Proper use of inhalers
Pulmonary drug delivery is the inhalation of drug formulation through
mouth and the further deposition of inhaled pharmacological agent in lower
airways is the main purpose of this drug delivery route.
Advantage20 Disadvantages

1. Large surface area is available for 1. Pulmonary airways having

absorption. mucous lining clears the
2. Close proximity to blood flow. deposited particles towards
3. Avoidance of first pass hepatics the throat.
metabolism. 2. Only 10-40% of the drug
4. Compared to other oral route smaller doses leaving the inhalation device
are required to achieve equivalent therapeutic (conventional) usually
effect. deposited in the lungs.
5. Provides rapid drug action. 3. It has short-lived duration
6. It can be employed as an alternative route of activity because drugs are
to drug interaction when two or more rapidly removed from the
medications are used concurrently. lungs or because of rapid drug
7. Provides local action within the respiratory metabolism.
tract.
8. Provides reduced dose.
9. Allows for a reduction in systemic side-
effects.

The devices most commonly used for respiratory delivery includes: (1)

conventional metered dose inhalers (MDI); (2) dry powder inhalers (DPI); and
(3) nebulizers. Within and between each group there are marked differences
with respect to design, construction, aerosol cloud generation, output
characteristics, deposition pattern of the inhaled particles, optimal inhalation
technique and ease of use. In addition to these variables, there are other factors
to consider when prescribing an inhaler i.e. many inhalers cannot be used at all
by young children or older people. 21
20
Niti Yadav , Alka Lohani, Dry Powder Inhalers: A Review, School of Pharmaceutical Sciences, IFTM University,
Moradabad-244001, India
21
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark
31
The most important questions to consider when prescribing an inhaler are: 22
(1) Which inhaler is the most simple and easiest to use optimally for various age
groups of patients?
(2) Which inhaler most reproducibly delivers the highest fraction of the
delivered dose to the intrapulmonary airways in different age groups using the
inhaler optimally? (this may vary from one drug to another).
(3) Which inhaler has the best clinical effect for a given systemic effect
(therapeutic ratio) in the day-to-day treatment?
(4) Which inhaler is preferred by the patient?

Dry Powder Inhalers

In DPIs, the drug particles (diameter of about 60 um) are blended with the
suitable large carrier (e.g. Lactose), to improve the flow properties and dose
uniformity and the dry powders are delivered to the lung through a device
known as Dry Powder Inhalers. 23 Most of the particles from dry powder
inhalers are too large to penetrate into the lungs. However, the turbulent
airstream created in the inhaler during inhalation causes the aggregates to break
up into particles sufficiently small to be carried into the lower airways. Thus the
effect of powder inhalers is dependent upon a certain minimum amount of
energy from the patient’s inhalation to create the correct particle size of the
drug. Up to a certain point, increases in flow rate will increase the number of
particles within the ‘respirable range’ and the clinical effect of the inhalation.24
Dry powder devices which operate at low inspiratory flow rate e.g., Diskhaler,
turbohaler, are clinically desirable for childrens and adults with decreased lung
function either because of age or disease.25
Ease of use26 For many years, DPIs have been single dose inhalers and therefore
less convenient but easier to use than the MDI. Some children have difficulties

22
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

23
Niti Yadav , Alka Lohani, Dry Powder Inhalers: A Review, School of Pharmaceutical Sciences, IFTM University,
Moradabad-244001, India
24
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

25
Niti Yadav , Alka Lohani, Dry Powder Inhalers: A Review, School of Pharmaceutical Sciences, IFTM University,
Moradabad-244001, India

32
with correct loading and splitting of the capsules when using the single dose
inhalers, particularly during episodes of acute wheeze. In accordance with this,
several recent studies have found that the new multiple DPIs are easier to use
and more convenient, so these inhalers are preferred to the single dose inhalers
and MDIs in school children. The main problem with multi-dose DPIs is to train
the patient not to exhale through the inhaler before the inhalation, since that will
blow out the dose of the inhaler. DPI's cannot be used with spacers; this may be
a disadvantage in patients who inhale large doses of steroids.

The inhalation technique27 is simple. The number of respirable particles and the
effect decrease with decreasing inspiratory flow rates. The inhalation effort and
the inhalation flow rate needed to generate a therapeutic aerosol vary between
different DPIs. Therefore, results obtained with one inhaler cannot be used to
characterize another. Until further studies are available, DPIs should preferably
not be used in children younger than 5 years who may not be able to generate
such high inspiratory flow rates and therefore benefit less than older children
DPIs are propellant-free , Less need for patient coordination, Less potential for
formulation problems, Less potential for extractable from device components,
Formulation stability. On the other hand they have many disadvantages that
include: Dependency on patient’s inspiratory flow rate and profile, Device
resistance and other design issues, Greater potential problems in dose

26
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark
27
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

33
uniformity, Less protection from environmental effects and patient abuse, More
expensive than pressurized metered dose inhalers, Not available worldwide.28

Nebulizers
Nebulizers are systems in which the liquid formulations are disperse using
compressed air or piezoelectric vibrations.29
It is not possible to deliver all the fluid as aerosol since some is trapped as a
dead or residual volume within the nebulizer - even after nebulization to
dryness, i.e. until no more spray is produced. Nebulizers work more efficiently
(deliver more drug) when higher volume fills are used. Furthermore, drug
delivery can be markedly improved by using breath-actuated nebulizers, which
deliver drug during inspiration alone. However, at present these devices are
expensive and complicated. Nebulizers are generally far less effective per mg
drug than other inhaler systems. Thus, higher doses are required to achieve the
same clinical effect. 30
Little coordination is required from the patient if continuous nebulization and a
face mask with holes are used. Therefore, nebulizers are simple to use.
However, compared with other devices, nebulizers are expensive, bulky,
inconvenient, time consuming, inefficient delivery systems and, with our
present knowledge, their use for daily treatment should be limited to patients
who cannot be taught the correct use of another device or for drugs which
cannot be delivered by any other inhaler system. In clinical practice, this means
some children younger than 3-4 years, mentally retarded patients and some
elderly patients. 31
The primary disadvantages of nebulizers are the length of time it takes to use
them (typically at least several minutes to set up, inhale and clean), external
power requirement, their size and weight may limit portability.32
28
Niti Yadav , Alka Lohani, Dry Powder Inhalers: A Review, School of Pharmaceutical Sciences, IFTM University,
Moradabad-244001, India
29
Niti Yadav , Alka Lohani, Dry Powder Inhalers: A Review, School of Pharmaceutical Sciences, IFTM University,
Moradabad-244001, India
30
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

31
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

32
Niti Yadav , Alka Lohani, Dry Powder Inhalers: A Review, School of Pharmaceutical Sciences, IFTM University,
Moradabad-244001, India

34
In spite of all the problems with nebulized therapy, nebulizers are still the
delivery system of choice in the treatment of acute severe asthma in all age
groups, even if the same results can often be obtained with other inhalation
systems. In the acute situation, it is advantageous that oxygen can be
administered through the nebulizer at the same time as the B2 agonist. 33
Finally, it must always be remembered to consider the patient’s wish, since
prescription of an inhaler which the physician likes but the patient does not is
likely to reduce compliance.34

9. Physiochemical Drug Interactions &

Incompatibilities

This tutorial discusses drug interactions from a

physicochemical rather than a pharmacological or
pharmacodynamics viewpoint. Sometimes the interaction is
beneficial and sometimes not.

There are several physicochemical causes of interactions. These include:

33
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

34
S. Bedersen, Inhalers and nebulizers: which to choose and why, Department of Pediatrics, Kolding
Sygehus, Denmark

35
  pH effects – changes in pH that may lead to precipitation of the drug,
change of solvent characteristics on dilution, which may also cause
precipitation
 cation–anion interactions in which complexes are formed
 chelation – in which a chelator molecule binds with a metal ion to form a
complex
 adsorption to excipients and containers – causing loss of drug interactions
with plastics – another source of loss of material
 protein binding – through which the free concentration of drugs in vivo is
reduced by binding to plasma proteins.

Drug–drug or drug–excipient interactions can take place before administration

of a drug. These may result in precipitation of the drug(s) from solution, loss of
potency or chemical instability. Under some circumstances they can occur even
in the solid state.
An incompatibility occurs when one drug is mixed with other drugs or agents
and produces a product unsuitable for administration either because of some
modification of the effect of the active drug, such as increase in toxicity, or
because of some physical change, such as decrease in solubility or stability.

1. pH effects:

The pH of a medium, whether in a formulation or in the body, can be a primary

determinant of drug behaviour.
- In vitro pH effects
Chemical, as well as physical, instability may result from changes in pH,
buffering capacity, salt formation or complexation. Chemical instability may
give rise to the formation of inactive or toxic products. This increase or decrease
in pH may then produce physical or chemical changes in the system.

- In vivo pH effects
Changes in the acid–base balance have a marked influence on the absorption
and thus on the activity of drugs. Ingestion of antacids, food and weak
electrolytes will all change the pH of the stomach. Weakly acidic drugs, being
un-ionised in the stomach, will be absorbed from the stomach by passive
diffusion. One might expect, therefore, that concomitant antacid therapy would
delay or partially prevent absorption of certain acidic drugs (Ex. Tetracyclines).
The main mechanism would be an increase in pH of the stomach, increasing
ionisation of the drug and reducing absorption. Sodium bicarbonate is one of the
most effective antacids in terms of neutralising capacity. It can greatly depress
the absorption of tetracycline.

36
Some acidic drugs (Ex. Levodopa), are known to be absorbed in the intestine, in
which case the co-administration of an antacid is not necessarily prohibited, as
its effects may be transitory. Levodopa is metabolised within the
gastrointestinal tract and more rapidly degraded in the stomach than in the
intestine, so the rate at which the drug is emptied from the stomach can affect its
availability. It has been suggested that, when an antacid is administered prior to
the drug, serum levodopa concentration is increased because it is transferred to
the intestine more rapidly.

2. Cation–anion interactions

The interaction between a large organic anion and an organic cation may result
in the formation of a relatively insoluble precipitate. Examples of Interactions
between drugs and ionic macromolecules include: Heparin sodium and
erythromycin lactobionate that are contraindicated in admixture which will lead
to reducing in the anticoagulant activity of heparin.

3. Chelation

The term chelation relates to the interaction between a metal atom or ion and
another species, known as the ligand. Chelation changes the physical and
chemical characteristics of both the metal ion and the ligand. It is simplest to
consider the ligand as the electron-pair donor and the metal the electron-pair
acceptor. When a drug forms a metal chelate, the solubility and absorption of
both drug and metal ion may be affected, and drug chelation can lead to either
increased or decreased absorption. Probably the most widely quoted example of
complex formation leading to decreased drug absorption is that of tetracycline
chelation with metal ions. The complexing of tetracyclines with calcium poses a
problem in paediatric medicine. Discoloration of teeth results from the
formation of a coloured complex with the calcium in the teeth; the deposition of
drug in the bones of growing babies can lead to problems in bone formation.
The decreased aqueous solubility of chelates suggests increased lipophilicity
but, in the case of the tetracycline chelates, precipitation would decrease the
biological activity of the drug as it would be less available for transport across
membranes; the larger molecular volume of the chelate would also prevent easy
absorption in the intact form.

4. Adsorption of drugs

- Adsorption to excipients

37
Adsorbents generally are non-specific so will adsorb nutrients, drugs and
enzymes when given orally. Several consequences of adsorption are possible. If
the drug remains adsorbed until the preparation reaches the general area of the
absorption site, the concentration of the drug presented to the absorbing surfaces
will be much reduced, resulting in a slower rate of absorption. A further
example is the delayed absorption of lincomycin (XX) when administered with
kaolin and pectinic acid (Kaopectate).

Loss of activity of preservatives can arise from adsorption on to solids

commonly used as medicaments. In solid-dosage forms, talc, a commonly used
tablet lubricant, has been reported to adsorb cyanocobalamin and consequently
to interfere with intestinal absorption of this vitamin.

- Adsorption to plastics

The plastic tubes and connections used in IV containers and giving sets can
adsorb or absorb a number of drugs, leading to significant losses in some cases.
Drugs that show a significant loss when exposed to plastic, in PVC, include
insulin, diazepam, vitamin A acetate …

Preservatives such as the methyl and propyl parabens present in formulations

can be sorbed into rubber and plastic membranes and closures, thus leading to
decreased levels of preservative and, in the extreme, loss of preservative
activity.

5. Protein binding

High levels of protein binding alter the biological properties of the drug as free
drug concentrations are reduced. Most drugs bind to a limited number of sites
on the albumin molecule. Binding to plasma albumin is generally easily
reversible, so that drug molecules bound to albumin will be released as the level
of free drug in the blood declines. Drugs bound to albumin (or other proteins)
are attached to a unit too large to be transported across membranes. They are
thus prevented from reacting with receptors or from entering the sites of drug
metabolism or drug elimination until they dissociate from the protein. Plasma
proteins other than albumin may also be involved in binding; examples of such
interactions are shown in the Figure.

38
Binding to protein outside of the plasma may determine the characteristics of
drug action or transport. Muscle protein may bind drugs such as digoxin and so
act as a depot. Differences in the bioavailability of two antibiotics following
intramuscular administration have been ascribed to differences in protein
binding. Dicloxacillin, 95% bound to protein, is absorbed more slowly from
muscle than ampicillin, which is bound only to the extent of 20%.35

35
Florence, A. T. and Attwood, D., Physiochemical Principles of Pharmacy in Manufacture, Formulation and
Clinical Use, Sixth Edition, Pharmaceutical Press, London, 1122 p.

39