ASSISTING SMALL SCALE COMPOUNDING

Preparing for production process

Learning out come
The student may able to know
1. what is the difference between Compounding and
manufacturing
2. Reasons for compounding
3. Compounding equipment
4. Principles of compounding
5. Calculations involved
Introduction
 Compounding; includes the preparation, mixing, assembling (collection),
packaging or labeling of a drug in response to a prescription written by a
licensed practitioner.
Extemporaneous compounding is defined as the timely preparation of a
drug product according to a physician’s prescription, a drug formula, or
a recipe in which calculated amounts of ingredients are made into a
homogenous (uniform) mixture.
Extemporaneous compounding is done when certain medical needs of
individual patients cannot be met by the use of an approved commercial
drug product
 Compounding
Pharmaceutical preparation of components into drug products that:
1. Are considered to be within the professional practice of pharmacy,
regulated by provincial regulatory authorities in accordance with
guidelines and standards that ensure the quality and safety of
pharmaceuticals;
2. . Involve a relationship that can be demonstrated to exist between a
patient and/or:
a) a regulated health care professional
b) a practitioner;
3. Do not circumvent regulatory requirements including
 The Food and Drugs Act and the Food and Drug Regulations,
 The National Drug Schedules, or intellectual property
legislation; and
4. Provide a customized therapeutic solution to improve patient care
without duplicating a commercially available, approved product.
Reasons for Extemporaneous Compounding
a. Unavailable dosages, strengths and routes of commercial products
b. Dilution of adult doses of medications to Pediatric/Geriatric strengths
c. Conversion of solid dosage forms to solutions or suspensions
d. Combination of topical dermatological products not available by the
manufacturer
 e. Inactive ingredients of commercial products which may cause allergic
reactions in individuals

Safety, personal hygiene and dress coding

Safety
-Proper use of compounding equipment such as
 Balances and measuring device
 Guidelines for selecting proper measuring devices, .
-Pharmaceutical techniques needed for preparing compounded dosage forms
e.g., levigation, titration, methods to increase dissolution, geometric dilution
-Properties of dosage forms see Pharmaceutical Dosage Forms in USP–NF to be
compounded and related Factors such as:-
 Stability, storage considerations, and handling procedures.
 Handling of nonhazardous and hazardous materials in the work area
 protective measures for avoiding exposure
 emergency procedures to follow In the event of exposure
 The location of Material Safety Data Sheets (MSDSs) in the facility.
- Use and interpretation of chemical and pharmaceutical symbols and
abbreviations in medication orders and in product formulation directions.
- Pharmaceutical calculations.
-Procedures should be established to verify the ability of staff to meet
established competencies.
These procedures may include observation, written tests, or quality control
testing of finished products.

Personal hygiene.

-Personnel engaged in compounding should wear clean clothing appropriate for

the duties they perform.
-Protective apparel, such as head, face, hand, and arm coverings, should be
worn as necessary to prevent contamination of products and to protect
workers.
-Generally, a clean laboratory jacket is considered appropriate attire for most
personnel performing
non sterile compounding activities.
-Personnel involved in compounding hazardous materials should wear safety
goggles, gloves, a mask or respirator, double gowns, and foot covers as
required, depending on the substance being handled.
-To avoid microbial contamination of compounded drug products, written
policies should be established that address appropriate precautions to be
observed if an employee has an open lesion or an illness.
-Depending on the situation, an affected employee may be required to wear
special protective apparel, such as a mask or gloves, or may be directed to
avoid all contact with compounding procedures.
-eating, drinking, chewing, or smoking in compounding room must be
prohibited
-Storage of food, drinking, smoking and personal medication in the
compounding areas must be prohibited

-Written procedures detailing the minimum requirements for health and

hygienic behavior of individuals performing compounding activities should be
addressed in a policy manual.
This should include, but not be limited to:
a. Suitable dress (e.g. gowns, masks, gloves, footwear);
b. Hand hygiene; and
c. Health conditions and open lesions

Preparation areas
1. It is not necessary that compounding activities be located in a separate
facility,
2. The compounding area should be located sufficiently away from routine
dispensing and counseling functions and high traffic areas.
3. The area should be isolated from potential interruptions, chemical
contaminants, and sources of dust and particulate matter.
4. To minimize chemical contaminants, the immediate area and work
counter should be free of previously used drugs and chemicals.
5. To minimize dust and particulate matter, cartons and boxes should not
be stored or opened in the compounding area.
6. The compounding area should not contain dust-collecting overhangs and
ledges (e.g., windowsills).
7. At least one sink should be located in or near the compounding area for
hand washing before compounding operations.
8. Proper temperature and humidity control within the compounding area
or facility is desirable.

Work areas
1. Should be well lighted, and work surfaces should be level and clean.
2. The work surface should be smooth, impervious, free of cracks and crevices
(narrow opening), and none shedding.
3. Surfaces should be cleaned at both the beginning and the end of each
distinct compounding operation with an appropriate cleaner or solvent.
4. The entire compounding facility should be cleaned daily or weekly (as
needed) but not during the actual process of compounding
Equipment.
1. The equipment needed to compound a drug product depends upon the
particular dosage form requested.
 Although boards of pharmacy publish lists of required equipment and
accessories, these lists are not intended to limit the equipment available
to pharmacists for compounding.

2 Equipment should be maintained in good working order.

 Pharmacists are responsible for obtaining the required equipment and
accessories and ensuring that equipment is properly maintained and
maintenance is documented.

Equipment used for compounding should:

a. Be situated in an area that permits it to function in accordance with
its intended use.
b. Equipment should be operated in a manner that prevents
contamination.
c. Be easily and routinely cleaned to minimize the potential for
contamination;
d. Be suitable for the preparation of the desired compound; and
e. Be kept clean, dry, and protected from contamination during storage
to prevent the addition of extraneous materials.
f. Equipment used for measuring and weighing should be calibrated, if
appropriate, on a regularly scheduled basis and documentation
showing proof of calibration and servicing should be maintained in
the pharmacy records.

Ingredients
 The pharmacist should be able to distinguish materials that require
specialized handling and storage, and demonstrate safe handling
techniques such as, but not limited to
a. Measuring or triturating in an appropriate environment
b. Donning the appropriate apparel
c. Ensuring that personnel handling the ingredients do so in a safe
manner
 The pharmacist should ensure the quality of the ingredients by using
products with a standard designation such as
 a. BP (British Pharmacopeia), USP (United States Pharmacopeia) or
NF (National Formulary) standard of quality; or
b. A valid lot number and beyond-use-date (if available). If expiry is
not available, a date of receipt should be recorded on the raw
material; or
c. A Certificate of Analysis (C of A) for raw materials that is
maintained in the records.
 Ingredients should be selected based on:
a. Solubility
b. Stability (provide an environment in which the ingredients are most
likely to resist chemical change or degradation)
c. Compatibility
d. Patient’s allergies, disease state, ability to administer, and other
medications;
e. Intended use
f. Duration of treatment
g. Potential drug-drug interactions
h. Medication administration frequency and
I. Route of Administration Selection of ingredients may also depend on
the dosage form to be compounded.

Factors to consider in selecting the dosage form include

(1) Physical and chemical characteristics of the active ingredient
(2) Possible routes of administration that will produce the desired
therapeutic effect
E.g. oral or topical
(3) Patient characteristics
E.g. age, level of consciousness, ability to swallow a solid
dosage form
(4) Specific characteristics of the disease being treated
(5) Comfort for the patient, and
(6) Ease or convenience of administration.

PHARMACEUTICAL MEASUREMENTS
Objective: To introduce the students to pharmaceutical measurements

Pharmaceutical preparations, as the final forms used for medication, must be

effective and safe. These requirements demand
 Quantitative accuracy andQualitative accuracy

1) Qualitative Accuracy
 Involves assuring the identity of ingredients by constant vigilance.It
requires
 (a) Reading labels carefully and doing this three times:
 When the container is taken from the shelf, when it is used, and
after it has been used
(b) Observing the appearance such as the color, shape and texture as
well as the odor of every ingredient

2) Quantitative Accuracy
 Involves confirming the amount of the ingredients to be exact
 Quantitative accuracy may be achieved by carefully
(a) Choosing the instrument (balance or measure) to be used in
relation to the amount of the ingredient, the nature of the
ingredient, and the degree of accuracy desired, etc.
(b) Reading the markings corresponding to the volume or weight
measured

 Accuracy of measurement, although important in either case, is more

important especially in hospital and community pharmacies than in
pharmaceutical factories
 This is because the latter involve frequent supervision and
therefore there is more chance for detecting failure of accuracy in
measurement
 Knowledge and application of accurate pharmaceutical measurements
are essential for pharmacists to practice their profession
 Pharmaceutical measurements mostly involve: Weighing and Measuring
Volumes

Weight

 Equally as important as the balance in the weighing process are the

mass standards, the weights
 Good weights are commonly made of polished brass and to increase
resistance to corrosion they may be plated with Nickel, Chromium, Gold
or Platinum
 Weights of high accuracy are also made of stainless alloys
 Small weights of less than 1g (500 mg to 50 mg) are made of Tantalum
and Aluminum for less than 50mg

Cares that should be taken in weighing

 Good technique in the weighing process is important to both accuracy

and prolonged usefulness of the equipment. Some of the rules that can
serve as guides are as follows
 o Keep the balance in a well-lighted place, as free as possible from
vibration, dust, moisture, corrosive vapors, wind, etc.
o Keep the balance cover down except when it is in use
o Keep the balance clean at all times (remove by a soft brush or a dry
clean towel)

o Use powder papers, and watch glasses or stoppered bottles (for

corrosive substances) to prevent direct contact of the pan(s) and the
material to be weighted
o Support the pan(s) at all times except when equilibrium is tested
 Weights and materials should never be added to or removed from
the pans unless the pans are supported
o Handle weights only with forceps because fingerprints increase their
weights or accelerate corrosion
o Adjust the scale to perfect balance (Zero position) before each weighing
 Failure to adjust the scale is the most common source of error
o Clean weights with a soft clean towel (when required) and if this is not
sufficient, use a paste of Precipitate Calcium Carbonate and Glycerin
followed by cleaning with a moistened towel and drying
Weighing Techniques for Torsion Balances

1. Adjust the balance by means of the leveling screws so that the index
pointer is at zero
2. With the balance arrested, open the balance lid (cover) and place the
desired weights on the right pan and the material to be weighed on
the left pan
3. Unlock the balance to observe if too little or too much material was
deposited
4. Using a spatula, remove or add material, arresting the balance each
time a transfer is made
5. When equilibrium is established, the balance should be arrested, the
lid closed, and the arrest released to check the equilibrium

 In dispensing (Hospital and Community Pharmacies), the type of balance

used is called prescription Balance
 There are two main types of Prescription Balances:
1) Class A Prescription Balance
E.g. Torsion Prescription balance
2) Class B Prescription Balance
 The major purpose being the same (i.e. weighing), balances are
differentiated from each other by the following parameters
 1) Sensitivity: Is the smallest weight that makes a perceptible
change in the pointer of a balance, which indicates the equilibrium
position
2) Sensitivity Requirement (SR): Is the weight necessary to move
the pointer of the balance one division on the index plate against
which equilibrium is observed
 SR for class A Prescription balance is 6 mg while that of
class B prescription balance is 30 mg
3) Capacity: Is the maximum weight which a balance can weigh
 The capacity of most Class A and Class B Prescription Balance is 120g
 In order to avoid errors of 5% or more, the minimum amount that can be
weighted on Class A Prescription Balance is 120mg and on Class B
Prescription Balance is 648 mg

Smallest Weight that can be weighted = SR X 100

Permissible Percent of Error
Major parts of a Balance
Pan(s) Spirit Level
Balance Pointer Screw Feet
Index Plate Balance Cover
Beam(s) Pan Support

Main weighing units used in pharmacy

Unit Abbreviation Gram equivalent
1 kilogram 1 kg 1000 g
1gram 1g 1g
1 milligram 1 mg 0.001 g
1 microgram 1 mg (or 1 mcg) 0.000 001 g
1 nanogram 1 ng 0.000 000
001 g

Example1 :-Convert 2.3 g into milligrams

To convert from grams to milligrams, multiply by 1000

2.3 *1000= 2300 milligrams

Example2 Convert 7894 milligrams into grams

To convert from milligrams to grams, divide by 1000.
7894 / 1000= 7.894 g

Example 3 Convert 3.2 nanograms into milligrams First convert from

nanograms to micrograms:

3.2 / 1000=0.0032 micrograms

Then convert from micrograms to milligrams:

0.0032 / 1000 = 0.000 003 2 milligrams

NB:-To convert between the base weight units, multiply or divide the figure by
1000
i.e Conversion from kilograms to nanograms multiply the figure by 1000
Conversion from nanograms to kilograms divide the figure by 1000

All balances have different accuracies, precisions and tolerances and it is

important that the correct balance is used for a particular weighing task. In
order to select the correct balance for a particular weighing task, the accuracy,
precision and tolerance of the balance need to be taken into consideration
Accuracy – is a measure of the capability of a balance to approach a true or
absolute value.
Precision – is the relative degree of repeatability,
i.e. how closely the values within a series of replicate measurements
agree.’
Tolerance – or ‘limits of permissible errors’ is the extreme value of an error
permitted by specifications for a measuring instrument

Practice 1. Weighing 10 g of Zinc Oxide BP powder on a Class II dispensing

beam balance
2. Weighing 10 g of Simple Ointment BP on a Class II dispensing
beam balance
3. Weigh 10 g of Zinc Oxide BP on an electronic balance
 LIQUID DOSAGE FORM PREPARETION

Volume

 It is possible to describe a given amount of matter by the quantity of

space it occupies (its volume), as well as by its weight
 But the custom is to measure amounts of liquids by volume and
solids by weight

 An important factor in the accuracy of an instrument used for measuring

volume is the surface area of the liquid in it
 Accuracy increases as surface area decreases. However, a decrease
in surface area decreases the convenience of transferring a liquid
to and from the equipment
o Therefore, accuracy and convenience should be
compromised
 Volume is measured by using measures

 There are several types of measures. Some of them are the

following
o Cylindrical Graduates (Graduated Cylinders)
o Conical Graduates
o Burettes
o Pipettes
o Droppers
o Volumetric Flasks
o Conical Flasks

Compounding project
General procedure for compounding
Criteria-
1. Wear personal protective (Gowon, Masks, Glove, etc) & hand washing.
2. Clean work row material and Ingredients
3. Collect row material and equipments
4. Tare bottles
5. Correct calculation
6. Weighing technique use of paper or watch glass
7. Measuring technique
8. Mixing /levigation of technique
9. Packaging choice of container
 10. Labeling
11. Clean work area.

Techniques of measuring liquids

 Good technique in measuring liquids involves the following points. The

instructions given below are for right-handed personnel

1. Choose the smallest measure that will hold the required volume. If
possible do not split the volume between two measurements because
this will increase the error
2. Hold the bottle with the right hand. Keep the label uppermost so that
it is visible during measuring and so that any trickles after use do not
obscure the label

3. Remove and hold the stopper of the bottle with the little finger of the
left hand. If it is not possible to hold the stopper, it should be placed
top uppermost on a clean tile to protect against atmospheric
contamination
4. Hold the graduate, which should be clean and dry, at the bottom with
the thumb and the forefinger, and support it on the curved middle
finger of the left hand. Don’t tilt the measure
5. Raise the graduate so that the required mark is level led with the eyes
to minimize errors in reading (Error or parallax)
6. Pour the liquid into the center of the graduate until the bottom of the
meniscus exactly reaches the required mark
 For very dark liquids, the true meniscus is often invisible and it is
recommended that such liquids should be measured by difference
7. Close the stock container and return it tidily to the shelf

Meniscus Volume

The volume above the horizontal tangent touching the lowest point of the
surface of a liquid is the meniscus volume

Main volume units used in pharmacy

Unit Abbreviation Litre equivalent
1 litre 1 L (or 1 litre) 1 litre
1 millilitre 1 Ml 0.001 litre
1 microlitre 1 Ml 0.000 001 litre

Example 1. Convert 6.7 litres into millilitres

To convert from litres to millilitres, multiply by 1000:

6.7 * 1000= 6700 millilitres

Example 2. Convert 3643 millilitres into litres

To convert from millilitres to litres, divide by 1000:

3643 / 1000 = 3.643 litres

Example 3. Convert 5.5 microlitres into litres

. First convert from microlitres to millilitres:

5.5 / 1000 = 0:0055 millilitres

Then convert from millilitres to litres:

0.0055/1000 = 0:000 005 5 litres
Conical measures
 In general, conical measures rather than cylindrical measures are used
in pharmacy practice
 They have a number of advantages over cylindrical measures.
For example:
 They are easier to fill without spilling liquid on the sides above the
required level
 It is easier to drain out the preparation.
 It is easier to rinse out the residue left after draining viscous
liquids into the preparation.
 They are easier to clean after use.
 On the other hand, it must be borne in mind that compared to
cylindrical measures, with conical measures:
 It is harder to read the meniscus accurately.
 It is more difficult to estimate volumes between graduations
(although in practice, owing to the error, this would be considered
poor professional practice and is never done)
NB. It is not good practice to use a conical measure to measure a volume that
is smaller than half of the total volume of the measure. Because of the shape of
the measure, it is more accurate, for example, to measure 10mL in a 10mL
conical measure than it would be to measure 10mL in a 100mL conical
measure. Stamped conical measures can be used to measure any marked
amount but it is sensible to select the smallest measure for the desired volume
Percentage strength
Expressing the strength of a pharmaceutical product by ‘percentage’ can have
a number of different meanings. These meanings are indicated by the addition
of suffixes, such as w/w or w/v, following the percentage symbol.
The following terms are commonly used:
* %w/w or percentage weight in weight (or%m/m – percentage mass in mass):
 This expresses the amount in grams of solute in 100 g of product.
* % w/v or percentage weight in volume:
 This expresses the amount in grams of solute in 100Ml of product.
* % v/v or percentage volume in volume:
 This expresses the number of millilitres of solute in 100mL of product.
* % v/w or percentage volume in weight:
 This expresses the number of millilitres of solute in 100 g of product.
The strength of solutions of solids in liquids is usually expressed as % w/v
and of liquids in liquids as % v/v.
When the type of percentage is not specified, by convention the above rule will
apply (i.e.% solid in liquid is interpreted as % w/v).

Parts and solubility

Parts
Another common method for expressing the strength of a pharmaceutical
product is through the use of the term ‘parts’, for example ‘parts’ of solute in
‘parts’ of product. This is interpreted as parts by weight (grams) of a solid in
parts by volume (millilitres) of the final solution; or in parts by volume
(millilitres) of a liquid in parts by volume (millilitres) of the final solution
Solubility
Solubilities are quoted in reference works in terms of the number of parts of
solvent by volume required to dissolve one part (by weight for solids or
volume for liquids) of the medicament in question.
The solubility value for a substance at 20 C is generally quoted unless
otherwise stated.

Reference texts often quote solubility in a range of solvents.

 For example, iodine is soluble 1 in 3500 of water, 1 in 125 of glycerol, 1
in 8 of alcohol and 1 in 5 of ether. In this case 1 g iodine would dissolve
in 3500mL water, whereas the same weight of iodine would dissolve in
only 5mL of ether
The process of dissolution in simple terms can be broken down into three
stages:
1 Removal of a molecule from the solute.
2 Preparation of a ‘space’ in the solvent ready for the transfer of the
dislodged solute molecule.
3 Positioning the solute molecule in the solvent space
.

Numerical value of different solubility descriptions

Solubility description Numerical value
Very soluble 1 in less than 1
Freely soluble 1 in 1 to 1 in 10
Soluble 1 in 10 to 1 in 30
Sparingly soluble 1 in 30 to 1 in 100
Slightly soluble 1 in 100 to 1 in 1000
Very slightly soluble 1 in 1000 to 1 in 10 000
Practically insoluble 1 in greater than 10 000

Example 1. What volume of potable water is required to dissolve 4 g of sodium

bicarbonate?
To calculate the required amount of solvent to dissolve 4 g of sodium
bicarbonate, you need to know the solubility of the solute.
The solubility of sodium bicarbonate in water can be found by reference to any
official text.
In the British Pharmacopoeia it is quoted as 1 in 11.
  This means that 1 g of sodium bicarbonate is soluble in 11mL of water.
 Multiplying the amount of sodium bicarbonate required in the
preparation by the solubility gives the quantity of solvent required:

4 * 11 = 44 mL of water
Example 2. What volume of potable water is required to dissolve 3 g of a solid
which is soluble in 2.5 parts of water?

1 g dissolves in 2.5mL of water.

Therefore, 3 g dissolves in 3*2.5 = 7.5mL of water.

Dilutions
 It is not uncommon for a compounder to have to dilute a concentrated
stock product to make either an ingredient for incorporation into a
pharmaceutical product or a product itself
• It is the required amount of concentrated product that needs to be
mixed with a specified amount of diluent.
• Pharmaceutical preparation are diluted by :
 By adding diluent
 Admixture with solutions or mixtures of lower strength.
• Pharmaceutical preparation are concentrated by:
 By addition of active ingredient
 Evaporation of diluent
 Admixture with solution or mixture of higher strength

 There are two main ways to express dilutions

(where ‘x’ is the volume in millilitres):
* 1 in x (e.g. 1 in 10)
* 1:x (or 1 to x) (e.g. 1:10 or 1 to 10).

It is important to understand the difference between these because they appear

initially to be the same.
However, any misinterpretation can lead to large errors of final concentration.

For example,
 a dilution expressed as 1 in 10 means that there is one part of solvent in
10 parts of final solution e.g. 1mL of concentrate and 9mL vehicle with a
final volume of 10 mL
  a dilution expressed as 1:10 means that there is one part of solvent to
10 parts of solvent (or 1 in 11)
e.g. 1mL of concentrate and 10mL vehicle with a final volume of 11 mL.
 In calculation involving dilution & concentration
 If ratio strength given convert into percentage strength
 Whenever there are proportional parts reduce them to the
least term i.e 25 parts : 75 parts to 1 parts : 3 parts
 to calculate the strength of solution prepared by diluting a solution of
known quantity and strength, an equation may be set as follows

How many ml of 0.02%(w/v) solution of phenyl mercuric chemical acetate can

be made from 125 ml of 0.2% solution?

Question
Prepare 500 mL of a 0.1% w/v solution using a 20% w/v concentrated stock
solution
First, you need to calculate the total amount of active ingredient required in
the final solution:
0.1% w/v solution = 0,1 g in 100 mL
Therefore, there is 0.5 g in 500 mL. Next, you need to calculate the quantity of
the concentrated solution that contains the same amount of active ingredient.
20% w/v solution 20 g in 100 mL So there are 2 g in 10 mL, 1 g in 5mL and
0.5 g in 2.5 mL. Therefore 2.5mL of a 20% w/v solution would be required to
make 500mL of a 0.1% w/v solution.
1; How many gram of opium containing 15%(w/w) of morphine and How
many gram of lactose should be used to prepare 150g of opium 10%(w/w)
morphine?
Q1= ? Q2= 150g Q1= 150g* 10%, 100g
C1= 15% C2= 10% 15%
150g- 100 = 50 g of lactose
REDUCTION AND ENLARGEMENT OF FORMULAS

• Most of the preparations made in a pharmacy are from proven formulas

that have been tested and are listed in the United State
Pharmacopeia/National Formulary (USP/NF) as official formulas.
• These formulas list the amount of each ingredient needed to make a
certain amount of the preparation.
 At times, it is necessary to reduce or enlarge a formula to satisfy the
needs of your pharmacy

RATIO AND PROPORTION METHOD

NOTE: Most of the time, the unknown factor will be the “Amount of each
ingredient
needed.”

b. Sample Problem: Using the official formula below, calculate the amount of
each ingredient needed to make 240 ml of Peppermint Spirit.
Peppermint Spirit
• Peppermint Oil............ 100 ml
• Peppermint Powder.........10 g
• Alcohol.....qsad.......... 1000 ml
 c. Knowing that qsad means to “add a sufficient quantity up to,” take 2.4 g of
peppermint powder, add 24 ml of peppermint oil, and add as much alcohol as
is necessary to make 240 milliliters.
The final product will be Peppermint Spirit

CONVERSION FACTOR METHOD

• The conversion factor method is the easiest and therefore the most
widely used method for reducing or enlarging formulas.
a. Find the conversion factor:

NOTE: The “Total Quantity Desired” and the “Total Quantity of Official
Formula” must have the same units so the units will cancel and yield a
conversion factor without units.
 (1) The first step is to find the conversion factor
120ml = conversion factor
1000ml
NOTE: The units, by being the same, cancel. 0.12 = conversion factor
 Formulation of liquid Dosage Forms

 Dosage forms are the means by which drug molecules are delivered to
sites of action within the body
Types of dosage forms
 Based on the physical nature of the products, dosage forms are classified
into three groups

1. Liquid dosage forms: Solutions, Suspensions and Emulsions

2. Semi-solid dosage forms: Ointments, Pastes, Creams, Jellies
3. Solid dosage forms: Powders, Granules, Capsules, Tablets,
Suppositories, etc.

Solutions

 Solutions are homogenous liquid preparations containing one or more

dissolved ingredients and are used for a variety of purposes as both
internal and external dosage forms
1. Solutions taken orally: mixtures, elixirs, syrups, linctuses, draughts
2. Solutions used in mouth and throat: mouth washes and gargles,
throat paints, throat sprays
3. Solutions instilled into body cavities: douches, enemas, eardrops,
eye drops, nasal drops, nasal sprays
4. Solutions applied to body surface: collodions, liniments, lotions, and
paints

 In addition to the active ingredients (medicaments), solutions also

contain vehicles and adjuncts
 The vehicle is the medium in which the ingredients of a medicine are
dissolved or dispersed for solutions (this is the solvent)
 E.g. Water, Aromatic waters, Alcohol, Glycerol, Syrup, etc
 Water is the vehicle of choice for the majority of pharmaceutical
solutions. This is because
o Water is generally available, relatively inexpensive, palatable
and non-toxic for oral use and non-irritant for external use
o It also acts as a solvent for a wide range of substances
 The adjuncts are additives that are added to improve the quality of the
preparations
 E.g. Chemical stabilizers, Colorants, Flavorants, Preservatives, etc

Dissolution Techniques
1. Check the solubilities of the ingredients from an official book
 Remember that some substances are less soluble at raised
temperatures, Paraldehyde being an example
2. Select a vessel in which to prepare the solution. A conical flask that will
hold the final volume of the preparation is the preferred vessel.
The advantages of conical flasks over other vessels are
a. Contents can be agitated by shaking with little risk of spillage
b. Contents can be readily heated if required
c. Contents can be readily cooled under running water with little
risk of admitting water to the solution
3. Powder the medicament (except for substances already in fine powder
form or for substances known to be freely soluble)
 A porcelain mortar is generally preferred for size reduction,
although glass mortars should be used for substances that paint
or stain
4. Weight the medicament. Note that powdering should precede weighing
because of the difficulty in removing all the dry powder from the mortar
 In order to avoid powdering a large excess of medicament, which
would then be wasted, an approximate weight plus a little excess
may be weighed and transferred to the mortar
 For readily soluble substances to be dissolved in the mortar,
powdering may follow weighing, e.g. Menthol in Eucalyptus oil
5. Agitate the solution. Shaking the flask or stirring with a glass rod will
aid solution
 For slowly soluble substances a mechanical stirrer is to be
preferred. A simple stainless steel propeller may be derived by a
variable speed electric motor
6. Heat the solution (only if necessary and if it does not damage the
medicament). Heating is appropriate for substances that are
a. More soluble at high temperature, e.g. KNO3
b. Not-heat labile
c. Non-volatile (unless special precaution are taken)
7. Check that solution is complete

Examine the solution critically for traces of undissolved solid on

the neck of the flask, in the bottom of the flask or in suspension in
the solvent
 Traces of powders on the inside shoulders or neck of the flask
must be washed into the bulk of the liquid
8. Restore the solution to room temperature (if necessary)
 Solutions that have been heated must be cooled before adjustment
to the final volume
9. Transfer to a measure and adjust to final volume
  It is more accurate to adjust to volume in a measure. However, for
very viscous preparations, e.g., linctuses, where transfer from a
measure to the container might leave a significant volume on the
inside of the measure (in spite of careful draining), adjustment may
be done in the container
 The container is placed on a flat surface and tarred by carefully
adding the correct volume of water and making the label of the
true meniscus with a small level

o Unless the preparation contains water, the calibrated

container must be drained well before use and, in some
instances, drying may be necessary

Practical

1. (a) Chloroform Water, B.P. 88

Ingredients Master formula
Chloroform ---------------------- 2.5 ml
Water FBC to ---------------------- 1000 ml
Send 100ml

(b) Double Strength Chloroform Water, B.P.88

Ingredients Master formula
Chloroform ----------------------- 5 ml
Water FBC to ----------------------- 1000 ml
Send 100ml
Compounding: Dissolve the chloroform in purified water by shaking

2. Peppermint Water
Ingredients Master formula
Peppermint oil --------------------- 0.2 ml
Water, FBC to --------------------- 100 ml
Send 50ml

Compounding: Dissolve the oil in purified water by shaking

3. Concentrated Camphor Water, BP. 88
Ingredients Master Formula
Camphor ----------------- 40 g
 Alcohol (90%) ----------------- 600 ml
Water, FBC to ----------------- 1000 ml
Send 50ml
Compounding: Dissolve the camphor in the alcohol. Then, add water
gradually in successive portions, vigorously shaking after each addition

4. Camphor Water, NF.

Ingredients Master Formula
Camphor ----------------- 2g
Water, FBC to ----------------- 1000 ml
Send 100ml

Compounding: Incorporate suitably comminuted camphor with 15g of

talc. Then, add the required volume of purified water and agitate
vigorously several times during 10 minutes period and filter

5. Concentrated Cinnamon Water, BP. 88

Ingredients Master Formula

Cinnamon oil ----------------- 20 ml
Alcohol (90%) ----------------- 600 ml
Water, FBC to ----------------- 1000 ml
Send 50ml

Compounding: Dissolve the oil in the alcohol. Add the water in

successive portions, shaking vigorously after each addition. Then, add
50g of talc. Shake occasional during few hours and finally filter

SPIRITS, TINCTURES AND MIXTURES

I. Spirits
 Spirits, also known as essences, are alcoholic or aqueous alcoholic
solutions of volatile substances. Like the aromatic water, the active
ingredients in the spirits may be a solid, liquid or gas. The volatile
substances in the majority of cases are volatile oils
 Some spirits are used internally for their medicinal value, a few
medicinally by inhalation. But a large number are used as flavoring
agents
 The amount of volatile material in spirits varies greatly and no fixed
percentage can be given. However, in all cased, the volatile oil content of
 the official spirits is much greater than that of the corresponding
aromatic waters

Preparation

Most spirits are prepared by simple solution in alcohol, although some can be
prepared by distillation, maceration, and chemical reaction methods
In preparing spirits, it must be kept in mind that the oils dissolved in alcohol,
are precipitated, causing turbidity when the solutions are mixed with water. In
order to avoid this turbidity, water, except as specified in the formula, should
be avoided
 Graduates and other equipment used should be thoroughly dry. Filter
paper should be moistened with alcohol
Storage
Spirits should be kept in well-closed containers and stored at temperatures not
exceeding 25oc. Good storage conditions prevent evaporation and volatilization
of either the alcohol or the active principle(s)

Practical
1. Peppermint Spirit, B.P.88 (peppermint Essence)

Ingredients Master Formula

Peppermint oil 100ml
Ethanol (90%) to 1000ml
Send 30ml.

Compounding: Dissolve the peppermint oil in ethanol. Add sufficient ethanol

to produce the final volume. If the solution is not clear, shake with previously
sterilized purified talc and filter
Action and Uses: The spirit is an effective carminative. Also, mixed with other
drugs or preparations, it may be used as a flavor

2. Benzaldehyde Sprit

Ingredient Master Formula

Benzaldehyde 10 ml
Ethanol (90%) 800ml
 Purified water to 1000ml
Send 50ml
Compounding:Dissolve the benzaldehyde in the ethanol and add sufficient
purified water to produce the final volume
3. Chloroform Spirit
Ingredient Master Formula
Chloroform 50ml
Ethanol (90%) 1000ml
Send 40ml

Compounding: Mix the chloroform with the ethanol

Uses and actions: Flavoring agent and preservative

II. Tinctures
 Tinctures are alcoholic or haydroalcoholic solutions of principles
extracted from natural sources or of pure chemicals merely dissolved in
these solvent systems, an example of the latter being Iodine Tincture
 Tinctures vary widely in their method of preparation, the strength of their
volatile ingredients, their alcoholic content and their intended use
 Tinctures are prepared by a number of processes: Maceration
(Process M), Percolation (process P) Solution, and Dilution Tinctures
should be stored in tight, light resistant containers protected from
direct sunlight and excessive heat

Practical
1. Iodine Tincture

Ingredients Master Formula

Iodine 25g
Potassium iodide 25g
Purified water 25mg
Ethanol (90%) to 1000ml
Send 50ml.
Compounding: Dissolve the potassium iodide and the iodine in the purified
water and add sufficient ethanol (90%) to produce 1000ml
Actions and uses: Antiseptic
2. Orange Tincture, BP,88
 Ingredients Master Formula
Dried Bitter-Orange Peel, in moderately fine powder 110g
Ethanol (70%) to 1000ml
Compounding: Percolation method
Use: Flavoring agent

III. Mixtures
 Mixtures are liquid oral preparation containing one or more active
ingredients dissolved and/or suspended in water or some other aqueous
vehicles such as aromatic waters
 Frequently, the term mixture is applied loosely to aqueous preparations
of description
 The U.S.P. does not recognize the term, mixture. The term,
suspension now is used to describe a number of similar
preparations
 Official mixtures are not usually formulated for a long shelf life and
should be recently prepared

Practical
1. Sodium Salicylate Mixture, BP, 88 (Sodium Salicylate Oral Solution)
Ingredients Master formula
Sodium Salicylate 50g
Sodium Metabisulfite 1g
Concentrated Orange Peel Infusion 50ml
Double Strength chloroform water 500ml
Water FBC, sufficient to produce 1000ml
M.Ft. M., Mitt. 50ml
Compounding: Dissolve the sodium salicylate and sodium metabisulfite in the
water. Add the concentrate orange peel infusion and the double strength
chloroform water. Finally adjust to the desired volume
Actions and Uses:Anti-inflammatory and Analgesic

2. Magnesium Sulfate Mixture, BP.88 (Magnesium Sulfate Oral Suspension)

Ingredients Master Formula
Magnesium sulfate 400g
Light magnesium carbonate 50g
Concentrated Peppermint Emulsion 25ml
 Double strength Chloroform Water 300ml
Water FBC, sufficient to produce 1000ml
M.Ft.M, Mitt. 50ml.
Sig. 10 ml t.i.d., shake the bottle before use
Compounding: Mix the magnesium sulfate and light magnesium carbonate in
a mortar and pestle and triturate the mixture with some water until a paste is
formed and then add the vehicle until the preparation becomes pourable.
Transfer the mixed mixture to a measureand add concentrated peppermint
emulsion. Finally adjust to the final volume with the water
Actions and Uses: A laxative
SYRUPS, ELIXIRS AND LINCTUSES
I. Syrups
 Syrups are concentrated aqueous solutions of sucrose, other sugars or
sweetening agents, to which small quantities of suitable polyhydric
alcohols, may be added to retard crystallization or to increase the
solubility of the other ingredients
 Syrups usually contain aromatic or other flavoring materials

 Medicinally, syrups are divided into two groups

 Flavoring syrups which are used as vehicles and
 Medicated syrups which contain ingredients giving them
therapeutic value
 Pharmaceutically, syrups are classified best according to their basic
formulas
 Those which are concentrated solutions of a sugar (Sucrose,
Dextrose) and

 Those which are formulated with artificial sweetening agents and

viscosity builders
 Generally, syrups are stored at room temperature (not exceeding 30 oC) in
tightly stoppered well-filled bottles

 Nearly saturated solutions of sucrose, if stored properly, are self-

preserving. But, in dilute solution, sucrose, as a carbohydrate, provides a
nutrient medium for the growth of microorganisms, particularly yeasts
and molds. Therefore, preservatives should be added if the concentration
of sucrose is significantly low

Practical

(1) Simple Syrup, U.S.P.

Sucrose --------------------647.4 g Sucrose --------------850 g
 Purified Water to ---------1000 g Purified Water to --1000 ml

Formulation:
 Simple Syrup, U.S.P. contains 85% w/v of sucrose, corresponding to
64.74% w/w. Its specific gravity is 1.313. The latter parameter provides a
ready means of standardizing the preparation
 A saturated solution of sucrose is 67.9% w/w at 25 oC; the British
Pharmacopoeia Syrup is 66.7% w/w sucrose
Methods of Preparation
A. Hot Process: Place the sucrose in a dish, add the water and dissolve the
sucrose by heating on a water bath, stirring continuously. When
dissolution of the sucrose is complete, allow the solution formed to cool
and add sufficient boiling purified water to make up for that lost by
evaporation. Then strain the syrup, while still warm, through a fine
muslin supported in a funnel into a bottle which is capable of nearly
filling, and shake the bottle occasionally until the content is quite cold
B. Cold Process: Place the sucrose in a suitable percolator the neck of
which is nearly filled with loosely packed cotton moistened, after
packing, with a few drops of water. Pour carefully about 450 ml of
purified water upon the sucrose, and regulate the outflow to a steady
drip of percolate. Return the percolate, if necessary, until all the sucrose
has dissolved. Then wash the inside and the cotton with sufficient
purified water to bring the volume of the percolate to 1000 ml and mix
C. Alternatively, the sucrose may be dissolved more rapidly in the proper
amount of water by agitation in a graduated bottle

N.B. Syrup made without heat is practically colorless while syrups made with
heat have pale amber color due to the levulose formed as a result of hydrolysis
of sucrose

(2) Chloral Syrup, B.P.C. 68

Ingredients Master formula
Chloral hydrate 200 g
Water, FBC 200 ml
Syrup to 1000 ml
Ft. Syrup, Send 20 ml
Sig. Two 5 ml h.s.
Compounding: Dissolve the chloral hydrate in the water, and add syrup to
volume
 Note: Chloral hydrate is volatile and sensitive to light, so the syrup must
be recently prepared
Actions and Uses: Hypnotic

(3) Ammonium Chloride Cough Syrup

Ingredients Master formula
 Ammonium chloride 4. 0g
Liquid Extract of Liquor ice 5.0 ml
Syrup 50.0 ml
Water q.s. to 100.0 ml
Ft. Cough Syrup 25 ml
Sig. 1tsp. t.i.d.
Compounding: Dissolve the ammonium chloride in portion of the water, and
add the liquid extract of liquorices, the syrup and water to adjust to volume
Actions and Uses: Expectorant
(4) Ferrous Sulfate Syrup, U.S.P.
Ingredients Master Formula
Ferrous sulfate 40 g.
Citric acid, hydrous 2.1 g
Peppermint spirit 2 ml
Sucrose 825 g
Purified water to 1000 ml
Ft. Syrup, Send 50 ml
Sig. Two 5 ml t.i.d.
Formulation: The peppermint spirit, used as the source of flavor, has a
persisting effect, which masks the somewhat unpleasant ferruginous taste of
the Fe2+. Care must be taken in preparing aqueous solutions of ferrous salts,
since Fe2+is readily oxidized by dissolved oxygen to form Fe 3+ which precipitates
as basic ferric salts; discoloring the solution. Ferrous sulfate is dissolved in
purified water containing some sucrose, which provides a reducing
environment thereby inhibiting auto-oxidation. If all of the sucrose were added,
the solution would be too viscous to allow perfect filtration. Citric acid is
included in the formulation to prevent discoloration of the syrup i.e. a change
from a green to a reddish brown tint; it does this by preferentially chelating Fe 3+

Compounding: Dissolve the ferrous sulfate, the citric acid, the peppermint
spirit, and 200g of the sucrose in 450ml of purified water, and filter the
solution until clear. Dissolve the remainder of the sucrose in the clear filtrate,
and add purified water to make 1000ml. Mix, and filter, if necessary through a
pled get of cotton
Actions and Uses: Haematinic
II. Elixirs
 Elixirs are clear, flavored oral liquids containing one or more active
ingredients dissolved in a vehicle that usually contains a high proportion
of sucrose or a suitable polyhydric alcohol or alcohols (glycerol,
Propylene glycol) and may also contain ethanol
 Elixirs generally owe their pleasant flavor to the presence of sugar and
the volatile flavoring agents. However, the sugar content of elixirs is lower
than that of syrups
  In general elixirs are reasonably stable preparations provided they are
stored in well-filled containers and are not diluted or mixed with other
preparations

Practical

(1) Phenobarbitone Elixir

Ingredients Master Formula
Phenobarbitone 0.4 g
Ethanol (90%) 40 ml
Compound orange spirit 2.5 ml
Glycerol 40 ml
Amaranth solution 1 ml
Purified water, to 100 ml
Ft. elixir, Send 25 ml
Sig. 2tsp. h.s., store in dark place
Formulation: Ethanol (90%) and glycerol are included as co-solvents for the
phenobarbitone. Compound orange spirit is used with the glycerol for flavor
and the amaranth solution for color
Phenobarbitone is virtually insoluble in water, but a clear product can be made
by dissolving it in alcohol and then diluting with glycerol and water
Compounding: Dissolve the phenobarbitone in the ethanol (90%) and add the
compound orange spirit before adding the glycerol, the amaranth solution and
water to volume
Actions and Uses: Anti-convulsant
Note:Phenobarbitonecauses drowsiness; alcohol should be avoided

2. Ephedrine Elixir, B.P.C.

Ingredients Master formula
Ephedrine hydrochloride 3.0 g
Glycerin 200.0 ml
Invert syrup 200.0 ml
Alcohol (90%) 00.0 ml
Purified water 60.0 ml
Chloroform Sprit 40.0 ml
 Amaranth solution 10.0 ml
Lemon Spirit 0.2 ml
Syrup to 1000.0 ml

Compounding: Dissolve the ephedrine hydrochloride in water, add the

glycerin, the Amaranth solution, the alcohol, the chloroform spirit, the lemon
spirit, the invert syrup and sufficient syrup to produce the required volume,
and mix

III. Linctuses
 Linctuses are viscous oral liquids that may contain one or more active
ingredients in solution. The vehicle usually contains large amounts of
sucrose, other sugars or a suitable polyhydric alcohol or alcohols
 Linctuses are intended for use in the treatment or relief of cough,
being sipped and swallowed slowly without the addition of water

Practical

1.Simple Linctus, B.P.

Ingredients Master formula
Concentrated Anise water 10 ml
Amaranth solution 1% 15 ml
Citric acid monohydrate 25 g
Chloroform spirit 60 ml
Syrup to 1000 ml
Send 40 ml
Sig. To be sipped and swallowed slowly undiluted
Formulation: The concentrated anise water, the citric acid and the chloroform
water act as flavoring agents, the amaranth solution as coloring agent and the
syrup as a demulcent vehicle---=
Compounding: The citric acid should be dissolved in the chloroform spirit,
conc. Anise water and amaranth solution before adding the syrup to volume
Action and Uses: Demulcent in the treatment of cough

SOLUTIONS USED IN THE MOUTH

(Gargles, Mouthwashes, Throat Paints, Throat Sprays)
I. Gargles
 Gargles are aqueous solutions intended for use in the prevention and/or
treatment of throat infection (by forcing air form the lungs through the
gargle, which is held in the throat)
  Gargles usually contain a bactericide, e.g. phenol or thymol, and are
dispensed in concentrated forms with directions for dilution with warm
water before use
Practical
1. Phenol Gargle (Carbolic Acid Gargle)
Ingredients Master formula
Phenol Glycerin 50 ml
Amaranth Solution 10 ml
Water to 1000 ml
Mitt. 50ml
Sig. Dilute with an equal volume of warm water before use
Not to be swallowed in large amounts

Compounding: Mix the phenol glycerin and the amaranth solution with
portion of the water. Agitate and add water to final volume
Actions and Uses: Antibacterial and anesthetic

2. Potassium Chlorate and Phenol Gargle

Ingredients Master Formula
Potassium Chlorate 30 g
Patent Blue V 0.01g
Liquefied phenol 15ml
Water to 1000 ml
Ft. garg. Mitt. 50 ml.
Sig. Dilute with ten times its volume of warm water before use
Not to be swallowed in large amounts
Compounding: Dissolve the potassium chlorate in about 35ml of warm water.
Cool before adding the liquefied phenol. Add the dye and make up to 50ml with
water
 Note: The most convenient way of obtaining the tiny amount of the
Patent Blue V required for this preparation is to use a stock solution.
Phenol is caustic so don’t use mouth to pipette phenol
Actions and Uses: Mild astringent and antibacterial

II. Mouth Washes

 Mouthwashes are aqueous preparations used to cleanse and deodorize
the buccal cavity for the purpose of oral hygiene and to treat infections of
the mouth
 Mouthwashes are particularly refreshing to bed-ridden patients; like
gargles, they are usually used after dilution with warm water and
directions for diluting the mouthwashes should be given on the labels of
these preparations
Practical
1. Compound Sodium Chloride Mouthwash
 Ingredients Master Formula
Sodium Bicarbonate 10g
Sodium Chloride 15g
Concentrated Peppermint Emulsion 25ml
Double Strength Chloroform Water 500 ml
Water to 1000 ml
Mitt. 50 ml.
Sig. Dilute with an equal volume of warm water before use
Compounding: Dissolve the sodium bicarbonate and the sodium chloride in
portion of the water. Add the conc. Peppermint emulsion and the double
strength chloroform water. Finally adjust to final volume with water
Actions and Uses: Cleansing and deodorizing

2. Alkaline Phenol Mouthwash

Ingredients Master Formula
Liquefied Phenol 30 ml
Potassium Hydroxide Solution 5% 30 ml
Amaranth Solution 1ml
Water to 1000 ml
Mitt. 50 ml.
Sig. Dilute with ten times its volume of warm water before use
Not to be swallowed in large amounts

Compounding: Mix the liquefied phenol, the potassium hydroxide solution,

and the amaranth solution. Then add water in successive portions while
agitating
3. Zinc Sulfate and Zinc Chloride Mouthwash
Ingredients Master Formula
Zinc Sulfate 20 g
Zinc Chloride 20 g
Compound Tartrazine Solution 10ml
Dilute Hydrochloric Acid 10ml
Chloroform Water, DS 500 ml
Water to 1000 ml
Send 50 ml.
Sig. Dilute with twenty times its volume of warm water before use

Compounding: Dissolve the zinc sulfate and zinc chloride in portion of the
water. Add the dilute hydrochloric acid, the compound tartrazine solution, the
chloroform water, DS and adjust to final volume with water
Note: Zinc chloride is very deliquescent and it is advantageous to keep the
container in a desiccators. Crush a stick quickly in a mortar, weigh the
required amount on a counterbalanced water glass and immediately return the
excess to the bottle, which should be tightly closed.

Zinc chloride usually contains some oxychloride, which makes the solution
turbid; this disappears when the dilute hydrochloric acid is added
Actions and Uses: Astringent
III. Throat Paints
 Throat paints are liquid preparations used for mouth and throat
infections by applying to the mucous surfaces. They are usually
medicated with substances possessing antiseptic, astringent, caustic, or
analgesic properties
 They are usually viscous (so, wide-mouthed containers should be used)
 Throat paints are applied by means of throat brush

Practical

1. Compound Iodine Paint (Mandl’s Paint)

Ingredients Master Formula
Potassium Iodide 25.0 g
Iodine 12.5 g
Alcohol 90% 40.0ml
Water 25.0ml
Peppermint Oil 4.0 ml
Glycerol to 1000 ml
Mitt. 40 ml.
Sig. Store in cool place. Shake the bottle before use
Not to be swallowed in large quantities

Compounding: Put the water into a 50ml conical measure. Dissolve the
potassium iodide (it dissolves very readily in water and need not be powdered).
Add the iodine and stir until completely dissolved. Although iodine is only
slightly soluble in water it is readily soluble in aqueous solution of iodides. In a
small measure, dissolve the peppermint oil in the alcohol and transfer it to the
iodine solution, and mix well. Make up to the volume with glycerol and mix
thoroughly. If the iodine solution is not well mixed with the glycerol the
preparation is streaky
 Note: Because of the high viscosity of the vehicle, this preparation is best
made entirely in a measure. For the same reason, an excess should be
prepared, since it is impossible to transfer the entire contents of the
measure to a bottle. A glass or a counterbalanced watch glass and a
vulcanite spatula must be used for weighing the iodine
Actions and Uses: Antiseptic in the treatment of pharyngitis and tonsillitis
IV. Throat Sprays
 Sprays are preparations of medicaments in aqueous, alcoholic or glycerol
containing media to be applied to the nose or throat by means of an
atomizer
 Apart from a few proprietary preparations containing antibiotics and
used for conditions such as laryngitis, pharyngitis and tonsillitis, most
solutions sprayed into the throat are intended to medicate the lungs

 Oily sprays have been used, but the oil retards the ciliary action
of the nasal mucosa. Also, drops of oil may enter the trachea and
cause lipoid pneumonia

Practical
1. Adrenaline and Atropine Spray, Compound B.P.C.
Ingredients Master Formula
Adrenaline Acid Tartrate 8g
Atropine Methonitrate 1g
Papaverine Hydrochloride 8g
Sodium Metabisulphite 1g
Chlorbutol 5g
Propylene Glycol 50ml
Purified water, FBC to 1000ml
Send 25ml.
Sig. To be used in a suitable nebulizer as directed
Discard if solution gets darkened

 Note: The required amounts of the adrenaline acid tartrate, atropine

methonitrate, sodium metabisulphite are small. So, use either a high-
grade analytical balance, or prepare titrations. For example, to prepare
titration of adrenaline acid tartrate: dissolve 300mg of the drug in
sufficient vehicle (water) to get 9ml solution, 6ml of which will be
equivalent to 200mg of adrenaline acid tartrate, the desired amount.
Similarly, titrations can be prepared for atropine methonitrate and
sodium metabisulphite
Compounding: Mix the three solutions (adrenaline acid tartrate, atropine
methonitrate, and sodium metabisulphite) and dissolve the papaverine salt in
the mixture. Dissolve chlorbutol in the propylene glycol and add the solution to
the mixture of salts. Filter if necessary and adjust to the final volume with
water
Actions and Uses: Bronchial relaxant used to relieve asthma and hay fever
 SOLUTIONS INSTILLED INTO BODY CAVITIES
(Douches, Enemas, Ear Drops, Nasal Drops, Nasal Sprays)
I. Douches
 A douche is an aqueous solution used for rinsing a body cavity and
functions as cleaning agent, antiseptic, or astringement
 The world douche in most often used for vaginal solutions but it is
sometimes applied to solutions for the bladder (usually called irrigations)
or the rectum (usually called enemas)
 Douches usually are directed to the appropriate body part by using bulb
syringes
 Douches are often supplied as liquid concentrates or powders to be
diluted or dissolved, in the appropriate amount of warm water, to the
correct strength and suitable volume (usually 1-2 liters) prior to use.
However, tablets for preparing solutions are also available
 If powders or tablets are supplied, they must be free from insoluble
material, in order to produce a clear solution. Tablets are produced by
the usual processes, but any lubricants or diluents used must be readily
soluble in water. Boric acid may be used as a lubricant and sodium
chloride normally is used as a diluents
 Tablets deteriorate on exposure to moist air and should be stored
in airtight containers

Practical

1. Potassium Permanganate Vaginal Douche

Ingredients Master Formula
Potassium Permanganates 1g
Water, F.B.C. to 1000ml
Mitt. 250ml
Sig. Dilute with three times its volume of warm water
Discard the remain after one week (7 days)
Store in cool place. Not to be taken

Note:Potassium permanganate solution will stain plastic surfaces; take

appropriate precautions. Care must be taken to avoid spillage during weighing,
and apparatus should be kept on a large glass or porcelain tile during
preparation of the solution
  The equipment and container must be spotlessly clean because this
solution will react with oxidizable residues and turn brown with loss of
strength
 The closure of the container must resist oxidation. Use a screw cap
containing a thick polythene wad. The old-fashioned glass stoppered
bottle is also suitable. Use a permanganate-resistant wad in the cap

Compounding: The solute dissolves slowly in water and since it may not be
heated, the use of an electric stirrer is recommended
As an alternative a glass mortar may be used. Transfer the medicament to a
glass mortar and grind the crystals with water.Allow undissolved crystals to
settle and pour supernatant to a flask. Add more water to the mortar, regrind
and decant, repeating these procedures until all the solid has dissolved and the
mortar is free from color. Finally, filter the solution through a clean sintered
glass filter and make up to volume through the filter
Action and uses: Mild antiseptic and deodorant
Advice for patients when dispensed:The solution stains skin, hair, fabric, etc
SOLUTIONS FOR EXTERNAL USE
(Collodions, Liniments, Lotions, Paints)
I. Collodions
 Collodions are liquid preparations containing pyroxylin (a nitrocellulose)
dissolved in a solvent mixture of ethyl ether and ethanol with or without
added medicinal substances
 Collodions, when applied to the skin, the solvent rapidly evaporates,
having a filmy residence of pyroxylin. This provides an occlusive
protective coating to the skin, and when the collodion is medicated, it
leaves a thin layer of that medication firmly placed against the skin
 Collodions are applied to the skin by means of a soft brush or other
suitable applicator and must be applied to dry tissues to affect adhesion
to the skin’s surface
 Collodions must be clearly labeled “For External Use Only” or with
words of similar effect
Storage: collodions should be kept in well-closed containers, at temperatures
not exceeding 30oC and remote from fire

2. Flexible Collodion
Ingredients Master Formula
Camphor 20 g
Castor Oil 30 g
 Collodion to 1000g
To make about 1000ml
Mitt. 10g
Sig. For external use only.
Store in a cool place, Highly flammable, keep away from naked flames

Note: Flexible collodion is prepared by adding 2% of camphor and 3% of castor

oil. The castor oil renders the product flexible, permitting its comfortable use
over normally moved areas, such as fingers or toes
Compounding: Weigh the ingredients, successively into a dry, tarred bottle.
Shake the mixture until the camphor is dissolved
Actions and uses: Skin protective

3. Salicylic Acid Collodion

Ingredients Master Formula
Salicylic Acid 120 g
Flexible Colodion to 1000ml
Mitt. 10ml
Sig. For external use only
Store in a cool place, Highly flammable, keep away from naked flames

Note: Salicylic acid collodion is a 10% solution of salicylic acid in flexible

collodion. It has keratolytic effects, especially in the removal of corns from the
toes. The preparation is applied one drop at a time onto the corn or wart,
allowing time to dry before another drop is added. Because salicylic acid can
be irritating to normal, healthy skin attention should be given to ensure
application directly onto the corn and wart. A useful preventive method is to
cover adjacent healthy skin with some white petrolatum prior to application of
the product.Proper tightening and storage of product after use is an absolute
necessity because of the vehicle
Compounding: Dissolve the salicylic acid in the flexible collodion
Actions and uses: Keratolytic in the treatment of corns and warts

II. Liniment
 Liniments are alcoholic or oleaginous solutions or emulsions of various
medicinal substances intended to be rubbed on the skin.
Liniments with an alcoholic or hydroalcoholic vehicle are useful when
rubefacient, counterirritant, or penetrating action is desired; oleaginous
liniments are employed primarily when massage is desired
  Liniments are not applied to skin areas that are broken or bruised
because excessive irritation might result, For external use only
 Liniments that are emulsions bear a label that says shake well before use
 Liniments should be stored in tight containers
 Depending on their individual ingredients, liniments are prepared in the
same manner as solutions,emulsions, or suspensions

Practical
. Methyl Salicylate Liniment
Ingredients Master Formula
Methyl salicylate 25 ml
Arachis oil 100 ml
Fiat:liniment.Mitt. 25ml
Sig. For external use only. Shake Before Use
Procedure: In a mortar, mix methyl salicylate with half amount of arachis oil,
mix well using the pestle.Transfer to a cylinder, and complete to volume with
the oil
Action and Uses: Methyl salicylate is absorbed through the skin and is applied
in liniments or ointments to relief pain in rheumatic conditions

III. Lotions
 Lotions are liquid preparations intended for external application to the
skin without friction (gently) by dabbing or after spreading on a dressing
 Most lotions contain finely powdered substance as the dispersed phase,
dispersedthrough the use of suspending and dispersing agents. Other
lotions have as the dispersed phase liquid substances that are
immiscible with the vehicle and are usually dispersed by means of
emulsifying agents or other suitable stabilizers
 Lotions should be shaken vigorously before each use to redistribute any
separated mater. Containers of lotions should be labeled to instruct the
patient to shake thoroughly before use and also to use externally only
Practical

1. Salicylic Acid Lotion

Ingredients Master Formula
Salicylic Acid 20g
Castor Oil 10ml
Alcohol (95%) to 1000ml
Mitt. 50ml
Sig. For external use only
Compounding: Dissolve the salicylic acid in portion of the ethanol; add the
castor oil and sufficient ethanol to produce 1000ml and mix
Actions and uses: Keratolytic for the treatment of dandruff

2. Copper and Zinc Sulfates Lotion

Ingredients Master Formula
Cooper Sulfate 15g
Zinc Sulfate 10ml
Camphor Water to 1000ml
Mitt. 50ml
Sig. For external use only

Compounding: Dissolve the copper sulfate and the zinc sulfate in the camphor
water
Actions and uses: Astringents in the treatment of impetigo

IV. Paints
 Paints are solutions or dispersion of one or more active ingredients for
application to the skin or, in some cases, mucous membranes. However,
all the official paints are solutions
 Skin paints often have a volatile solvent that evaporates quickly to have a
dry or resinous film of the medicament
 All paints, except throat paints, are labeled “For external use only”

Practical

1. Brilliant Green & Crystal Violet Paint

Ingredients Master Formula
Brilliant Green 5g
Crystal Violet 5g
Alcohol (90%) 500ml
Camphor Water to 1000ml
Mitt. 50ml
Sig. For external use only
Note: Precautions to prevent spillage during dispensing are particularly
necessary when a preparation contains a dye. Dyes are often light, fine
powders that easily float into the air if carelessly handled. The spatula used for
weighing should not be wiped with a cloth but should be washed before putting
down
Compounding: Dissolve the brilliant green and the crystal violet in the alcohol
and add sufficient water to produce the required volume
Actions and uses: Antiseptic to sterilize the skin in gynecology

2. Crystal Violet Paint

Ingredients Master Formula
Crystal Violet 5g
Water to 1000ml
Mitt. 50ml.
Sig. For external use only. Apply undiluted
Compounding: Dissolve the crystal violet in the water to produce the required
volume
Actions and uses: Antiseptic in the treatment of wounds and burns

SUSPENSION
 Suspensions are disperse systems in which finely divided drug particles
(called the disperse phase) are distributed throughout a vehicle (called
dispersion medium or continuous phase) in which the drug exhibits a
minimum degree of solubility. It includes both powders in dry form to be
placed in suspension and drugs suspended in liquid vehicles
 Suspensions can be classified into coarse suspensions in which the
particles are larger than 1m in diameter and colloidal suspensions in
which the particles may be considerably less than 1m in diameter
 Major applications
 Suspension dosage forms can be administered orally, injected
parenterally (intramuscularly or subcutaneously) or applied
externally (topically) to the skin, eye, ear, etc
 The physical properties of suspensions and their design depend upon the
nature of the dispersed phase, the dispersion medium and the
pharmaceutical adjuncts/additives

 The drug particles (dispersed phase) in a suspensions could be

 Diffusible solids
 In diffusible solids, or
 Poorly wettable solids
General Method of Preparation of Suspensions

1. Carefully tare(calibrate) the container to the required volume

2. Finely powderany solid ingredients not already in fine powder
3. Mix the insoluble powders in a mortar, adding first the ingredient of
smallest bulk and diluting it with the others in increasing order of bulk,
 using amounts approximately equal to bulk already in the
mortar(Geometric dilution)
4. Add enough vehicles to produce a smooth paste
5. Add non-volatile solid ingredients dissolved in part of the vehicle and mix
well
6. Dilute with a vehicle until pourable. Examine the suspension critically
and, if it contains foreign particles, strain through muslin (Before use,
rinse the fabric with a little vehicle to detach loose fibers)

7. Transfer it to the tared bottle. A measure is not used because complete

and accurate transfer of a suspension is not possible once it has been
made up to volume
8. Add any volatile solid ingredients, previously dissolved in some of the
vehicle, and mix well
9. Add any liquid ingredients; rinse the measures and mix well after each
addition
10.Rinse the mortar and pestle with successive volumes of the vehicle until
they are quite clean, transferring the rinsing to the bottle
11. Make up to volume with the vehicle and shake thoroughly

Containers and Labeling

 Suspensions are generally packed in well-closed containers appropriate
to the class of dispensed medicine be it mixture, lotion, ear drop, enema,
etc
 If the preparation is particularly viscous, a wide mouthed container (jar)
may be used
 Containers of suspensions should be of suitable size to allow shaking of
the products
 Labels for suspensions include
 Shake well before use
 Store in cool place (not refrigerator)
 Also expiry dates for suspensions that should be prepared recently
is one month and, if diluted, two weeks

A. Suspensions Containing Diffusible Solids

  Diffusible solid (also called dispersible solids) are light and easily
wettable solids. They readily mix with water and, on shaking, diffuse
evenly through the liquid for long enough for a dose to be measured
(Ensure even distribution in each dose)
 Examples of diffusible solids are light Kaolin, magnesium trisilicate,
light magnesium carbonate, and calcium carbonate

Practical
1. Pediatric Kaolin Mixture, BP 1988
Ingredients Master Formula
Light Kaolin 200 g
Amaranth Solution 10 ml
Benzoic Acid Solution 20 ml
Raspberry Syrup 200 ml
Chloroform Water (D.S.) 500 ml
Water to 1000 ml
M.S.A., Send 50ml
Sig. 1tsp t.i.d.
Formulation:The kaolin should preferably be sterilized to remove any
contaminating soil pathogens. Kaolin is a diffusible solid and therefore no
additional suspending agent is required, although the raspberry syrup
increases the viscosity of the vehicle

Benzoic acid solution and chloroform water act as preservatives. The raspberry
syrup provides a flavor and amaranth solution color, which is attractive to
children
Compounding: First tare the final container because if the preparation is made
up to volume in a measure, it is difficult to transfer it satisfactorily to a bottle.
The preparation should be made in a mortar of sufficient size to allow for
adequate mixing of the product. Add the kaolin to the mortar and prepare a
paste with the syrup and a little of the chloroform water. Add the amaranth
solution and mix well. If the dye is added at a later stage in the preparation, it
will not penetrate into the powder and white specks will be visible in the final
product. Dilute the suspension until pourable and transfer to the bottle.
Although it is advisable to add volatile ingredients such as chloroform water to
the bottle rather than the mortar, care should be taken to incorporate all the
chloroform water before making up to volume with water. Add the benzoic acid
solution to the bottle and make up to the final volume and shake thoroughly
Storage and shelf life: Unless the kaolin has been sterilized, the preparation
should be recently prepared
Container: Amber medicine bottle
Advice for patients when dispensed: Shake the bottle

Maintain fluid intake during diarrhea. If the product is counter-prescribed, the

patient should seek medical advice if the condition persists
Actions and uses: Anti-diarrhea mixture for children
2. Magnesium Trisilicate Mixture, BP 1988 (Magnesium Trisilicate Oral
Suspension)
Ingredients Master Formula
Magnesium Trisilicate 50 g
Light Magnesium Carbonate 50 g
Sodium Bicarbonate 50 g
Conc. Peppermint Emulsion 25 ml
Chloroform Water (D.S.) 500 ml
Water to 1000 ml
M.S.A., Send 50ml. Sig. 2tsp t.i.d.

Formulation: Magnesium trisilicate and light magnesium carbonate act as

antacids and adsorbents in the GIT. Sodium bicarbonate is a rapidly acting
antacid. Peppermint provides flavoring and acts as a carminative and
chloroform water acts as flavoring, preservative and vehicle. Both the
magnesium powders are diffusible and no extra thickening agent is required
Compounding: First tare the final container and select a mortar of sufficient
size to allow for adequate mixing of the product. Add the sodium bicarbonate to
the mortar and mix with the two insoluble powders by doubling the bulk on
each addition. This method is to be preferred to making a separate solution of
the sodium bicarbonate, which is time consuming. Add enough vehicles to
make a smooth paste and dilute with the vehicle until sufficiently pourable to
transfer to the bottle. The volatile peppermint emulsion should be added to the
bottle before making up to final volume

 The mixture may also be prepared from a pre-packed mix of the three
powdered ingredients with the addition of the appropriate amount of
peppermint emulsion and chloroform water
Storage and Shelf life: The mixture should be recently prepared
Container: Amber medicine bottle
Advice for patients when dispensed: Shake the bottle
The mixture may be taken alone or with water or other fluid between meals. If
counter-prescribed, the patient should seek medical advice if the condition
persists.
 Note: The mixture contains relatively high concentration of sodium ions,
which may be inappropriate for some patients
Actions and uses: Antacid used to treat dyspepsia
 SUSPENSIONS (CONTINOUS)
B. Suspensions containing indiffusible solids
 Indiffusible solids will not remain evenly distributed in a vehicle long
enough to ensure uniformity of dose
 Examples include chalk, zinc oxide, calamine, aspirin, and
phenobarbitone
 The simplest way of correcting this problem is to increase the viscosity of
the vehicle by adding a thickening agent which delays sedimentation by
impending fall of particles under gravity and by obstruction particle
collision, which leads to the formation of aggregates that settle rapidly
 The thickening agents used to stabilize suspensions are substances that
spontaneously form colloidal dispersions in aqueous media because of
their affinity to water. There are three major groups of thickening agents:
1.Polysaccharides include acacia, tragacnath, methylcellulose, sodium
alginate, microcrystalline cellulose, sodium carboxymethyl
cellulose, Starch, etc.
2. Inorganic agents include bentonite, veegum, hectorite,
aluminiumhydroxide, etc
3. Synthetic agents include carboxyvinyl polymer (Carbomer), colloidal silicon
dioxide, etc
Method of Preparation
Mix the thickening agent as a dry powder with the other insoluble powders in
the formula. Then make a smooth past and continue as in the general method.
Alternatively, the suspending agent, previously dispersed in water to form
mucilage, is levigated with the insoluble powders

Practical
1. PhenolatedCalamin Lotion, USP
Ingredients Master formula Reduced formula
Calamine 80g
Zinc Oxide 80g
Bentonite 20g
Glycerin 20ml
Liquefied Phenol. 10ml
Calcium Hydroxide solution to 1000 ml
Mitt. 50ml
Formulation: Calamine (basic ZnCo3 Suitably colored with Fe2O3) and zinc
oxide are mildly astringent and soothing to the skin. Both are indiffusible
solids and therefore bentonite is included as thickening agent, make the
formulation very difficult to pour from the bottle. Calcium hydroxide solution is
included to make the preparation more pourable. Liquefied phenol acts as a
preservative and glycerol as emollient (assists application), miscible with the
aqueous vehicle
 Note: Liquefied phenol is very caustic so do not use mouth to pipette the
liquid. Use a small measuring cylinder or a treated pipette

Compounding: First, tare the final container and select a large mortar. Mix the
dry powders in the mortar until evenly dispersed. It is important that the
bentonite is well distributed in the indiffusible powders.
Use the calcium hydroxide solution to make a smooth paste and to dilute the
formed paste for transfer to the bottle. Add the glycerol and liquefied phenol to
the bottle and make up to final volume with the vehicle
Storage and shelf life: The preparation is stable, cool storage is advised
because of the volatile preservative
Advice for patients when dispensed: Shake the bottle; For external use only.
The lotion is applied to the skin as required and allowed to dry
Actions and Uses: Cooling lotion useful for treating mild sunburn
2. Pediatric Chalk Mixture, B.P.1988 (Pediatric Chalk Oral Suspension)
Ingredients Master formula Reduced formula
Chalk 20g
Powdered Tragacanth 2g
Conc. Cinnamon Water 4ml
Syrup 100ml
Chloroform Water (D.S.) 500ml
Water to 1000ml
Mitt. 50ml
Formulation: Chalk is an indiffusible solid and tragacanth is included as a
suspending agent. Cinnamon provides flavoring and also acts as a carminative.
Syrup provides sweetening and adds to the viscosity of the product and
chloroform water acts as flavor, preservative and vehicle
Compounding: First tare the final container and select a mortar of sufficient
size to allow for adequate mixing of the product
 Mix the chalk and tragacanth in the mortar and prepare a paste with the
syrup and a little of the vehicle. Dilute until pourable and transfer to the
bottle.Add the other ingredients to the bottle and shake well before
making up to final volume or
 Put the chalk in the mortar and the tragacanth mucilage in small
amounts triturating to produce a smooth paste. Dilute with the vehicle
 until pourable and transfer to the bottle. Add the other ingredients to the
bottle and shake well before making up to final volume
Storage and shelf life: The preparation should be recently prepared
Container: Amber medicine bottle
Advice for patients when dispensed: Shake the bottle
Maintain fluid intake during diarrhea. If the product is counter prescribed, the
patient should seek medical advice if the condition persists
Actions and uses: Anti-diarrheal mixture for children

Mucilage
1. Tragacanth Mucilage BPC 1973
Ingredients Master formula Reduced formula
Tragacanth, finely powdered 12.5g
Alcohol (90%) 25ml
Chloroform Water 1000ml
Mitt. 100ml.
Formulation: The alcohol is used as a dispersing agent because it is poorly
absorbed by the gum. The chloroform water acts as a preservative
Compounding: On a small scale, the mucilage is conveniently made by
shaking the ingredients together in a jar calibrated to 100ml.Measure 95ml of
the vehicle and have to hand. Put the alcohol into the jar and then add the
tragacanth powder (The order of addition is important, i.e., reverse order may
lead to lumpiness). Mix and speed the resulting suspension around the inside
of the jar. Pour in the 95ml of the vehicle as quickly as possible, put on the
closure and shake without delay. Success depends on speed. Any vehicle
spilled on the outside of the jar can be replaced within making to volume. A
product that appears lumpy at first will become homogenous on standing for a
few days
Container: Amber bottle
Actions and uses: Suspending and thickening agent
2. Starch Mucilage, BPC 1973
Ingredients Master formula Reduced formula
Starch 25g
Water to 100ml
Mitt. 100ml
Compounding: Triturate the starch with 20ml of the cold water in a small
beaker or small mortar. Heat the remaining 80ml of water to boiling in a wide-
mouthed conical flask or beaker. Pour the cold suspension into the center of
the boiling water and reheat to boiling water with constant stirring. The
resulting gelatinized mucilage should be free from lumps. Immediate rapid
cooling prevents the formation of a skin. The cooled preparation may be
transferred to a measure and the water lost by evaporation replaced to volume
Storage and shelf life: The preparation should be used at once
Advice for patients when dispensed: Not applicable
Actions and uses: Suspending and thickening agent
C. Suspensions Containing Poorly Wettable Solids
 Some substances are both insoluble in water and poorly wetted by it.
When dispersion in water is prepared, it is difficult to disperse. Clumps
and the foam produced by shaking tend to persist because it is stabilized
by the film of unwettble solids at the liquid/solid interface
 To ensure satisfactory wetting, the interfacial energy between the solid
particles and the liquid must be reduced.

 This may be achieved by adding a suitable wetting agent which is

absorbed at the solid/liquid interface in such a way that the affinity of
the particles for the surrounding medium is increased while the inter-
particular forces are decreased, i.e., deflocculation occurs
 Surface-active agents such as wetting agents for external application
includes quailliatincture and sodium lauryl sulfate. For oral
administration, the less toxic polysorbates andsorbitan esters are
preferred. Hydrophilic colloids such as acacia, tragacanth and the
alginates will also act as wetting agents by coating solid hydrophobic
particles and imparting a hydrophilic character. These substances also
cause deflocculation of particles and imparting a hydrophilic character.
 These substances cause deflocculation of particles in suspension,
especially at low concentration
Properties of flocculated and deflocculated particles in suspension

Deflocculated Flocculated
1.Particles exist in suspension as Particles form loose aggregates
separate entities
2.Rate of sedimentation is slow, since Rate of sedimentation is high, since
each particle settles separately and particles settle as a floc, which is a
particle size is minimal collection of particles
3.A sediment is formed slowly A sediment is formed rapidly
4. The sediment eventually becomes The sediment is loosely packed and
very closely packed, owing to weight possesses a scaffold like structure.
of upper layers of sediment material. Particles do not bond tightly to each
5.Repulsive forces between particles other and a hard, dense cake does not
are overcome and a hard cake is form
formed
6. The suspension has a pleasing The suspension is somewhat unsightly,
appearance, since the suspended due to rapid sedimentation and the
material remains suspended for a presence of an obvious, clear
relatively long time. The supernatant supernatant region. This can be
also remains cloudy, even when minimized if the volume of sediment is
settling is apparent made large. Ideally, volume of sediment
should encompass the volume of the
suspension

EMULSIONS

 An emulsion is a disperse system consisting of two immiscible liquids,

usually water and oil, one of which (the disperse phase) is distributed
throughout the other (the continuous phase) as small globules
 Since this type of dispersion is inherently unstable, the system is
stabilized by the presence a third component, the emulsifying agent
(emulgent, emulsifier)

Types of Emulsions

 Emulsions can be classified into

1. Oil in water (O/W), in which the oil is dispersed in the water, i.e. the
continuous phase is aqueous)
 2. Water in oil (W/O) in which the water is dispersed in the oil, i.e. the
continuous phase is oily
3. Multiple emulsion, which could be of W/O/W or O/W/O
 Micro-emulsion:If the dispersed globules are of colloidal dimension
(1nm-1m diameter), the preparation which is quite often transparent is
called a micro-emulsion

Determination of Emulsion Type

 Tests for distinguishing between O/W and W/O emulsions include

1. Dilution Test (Miscibility Test): It involves dilution of an emulsion
with water or oil
2. Dye-solubility Test (Staining Test): It involves the use of dyes
soluble only in either the aqueous or the oil phase of an emulsion, but
not in both phases, e.g. Scarlet red, Sudan III
3. Conductivity Test: It uses the fact that an O/W emulsion possesses
a much higher conductivity that a W/O emulsion

Stability of Emulsions

 A stable emulsion is one in which the globules

 Retain their initial character (i.e., mean size and size distribution);
and
 Remain uniformly distributed throughout the continuous phase

 Instability in emulsion includes

1. Cracking (Breaking): coalescence of the dispersed globules and separation of
the disperse phase as a separate layer. In an emulsion, that has broken;
simple mixing fails to re-establish the stable emulsion
2. Creaming: the formation of a layer of relatively concentrated emulsion. It is
a less serious type of instability than cracking because a creamed emulsion
may be made homogenous again by shaking. Nevertheless, it is undesirable
because the closeness of the globules in the cream favors breakdown of
interface and consequent coalescence of the globules. Large droplets cream
 more rapidly coalesce more readily in the cream; therefore, the emulsion
may eventually crack
3. Phase inversion: the change of an emulsion from O/W to W/O emulsion or
vice versa.

Small-Scale Preparation an Emulsion

 Good emulsions can be prepared on a small scale using a mortar and

pestle although its efficiency is limited and the globule size may be larger
than 10µm
 Electric Mixer may also be used on a small scale although entrapped air
may be a problem
 Since the quality and stability of the product is improved by decreasing
globule size and by reducing the size range of globules in the disperse
phase the use of homogenizers recommended
 Mortar and pestle: This approach is used for those emulsions that are
stabilized by the presence of a multimolcular film (e.g., Acacia,
tragacanth, agar, and chondrus) at the interface. There are two basic
methods
i) The Wet Gum (or so-called English Method). In this method, the
emulsifying agent is placed in the mortar and dispersed in water
to form mucilage. The oil is added in small amounts with
continuous trituration, each portion of the oil being emulsified
before adding the next increment
ii) The Dry Gum (or so-called continental Method). In this method,
preferred by most pharmacists, the gum is added to the oil,
rather than the water as with the wet gum method
The only difference between the Continental and dry gum methods is
the proportions of constituents within the primary emulsion for example,
 Fixed oil emulsions made by the Continental method would use a ratio
of 4:3:2 rather than 4:2:1 with the dry gum method
 In both the Dry Gum and the Wet Gum methods, a primary, or
concentrated, emulsion is first prepared using a set ratio of oil, water,
and gum (emulsifying agent) from which the final product is obtained by
dilution with the continuous phase
Acacia Emulsions

 Unless otherwise specified, extemporaneously prepared emulsions for

internal use are made with acacia gum.
  To prepare acacia emulsions using a pestle and mortar, a thick (primary)
emulsion must be made first. The quantities for primary emulsions have
been determined by experience
 ‘Parts’ is interpreted as parts by volume for fixed, mineral, and volatile
oils, and part by weight for oleoresins and acacia

Quantities for Primary Emulsions

Types of oil Examples Quantities for primary emulsions (Parts)
Almond oil Oil Water Gum Tragacanth
Fixed oil (Acacia)
Arachis oil
Castor oil 4 2 1 0.1
Cod-liver oil
Mineral oil Liquid paraffin 3 2 1 0.1
Volatile oil Turpentine oil
Cinnamon oil 2 2 1 0.1
Peppermint oil
Oleo-resin Male fern extract 1 2 1 0.1

 NB. The amount of trangacanth needed is only one-tenth of the acacia

amount
 When an emulsion contains two or more oily liquids, the quantity
of acacia for each is calculated separately and the sum of these
quantities used

 The method is as follows

1. Measure the oil very accurately in a dry measure: pour it into the
bottom of a large, perfectly dry, flat bottomed mortar and allow the
measure to drain by resting it against the head of a dry flat-headed
pestle placed in the mortar
2. While the oil is draining, measures the quantity of water or aqueous
vehicle required for the primary emulsion in a clean measure and
place this within easy reach
3. Weigh the acacia powder
4. Remove the oily measure from the mortar: place the gum on the oil
and mix lightly for just long enough to disperse the lumps. Take care
to keep the suspension in the bottom of the mortar. Do not over mix
5. Immediately add all the previously measured water and stir
continuously but lightly in one direction until the mixture thickens
 under the pestle. Then triturate vigorously (i.e., Stir and mix
vigorously in the mortar)
6. When the primary emulsion is well formed there is usually a
characteristic ‘Cracking’ sound. Continue to triturate for a further 2-3
minutes to produce a white, stable emulsion. The finer the dispersion
the whiter the product
7. Gradually dilute the primary emulsion with small volumes of the
vehicle ensuring complete mixing between additions
8. Transfer to a measure and make up to final volume
9. If necessary, decant through a muslin strainer into a calibrated bottle

Problems:
 Sometimes the primary emulsion does not form properly and the
contents of the mortar become oily, thin and translucent. This is due to
phase inversion, the product, which has become a W/O emulsion cannot
be diluted with water and must therefore be discarded
 Possible causes are
 Insufficient shear between the mortar base and the pestle head
 Inaccurate measurement of water or oil
 Cross contamination of water or oil
 Excessive mixing of oil and gum
 Too early or too rapid dilution of the primary emulsion
 Poor quality acacia
Containers and Labeling
Emulsions should be supplied in well-filled containers with airtight closures.
For viscous preparations wide-mouthed amber glass bottles are most
appropriate
Labeling: Shake the bottle, store in cool place but avoid freezing
There are a number of advantages and disadvantages associated with the use
of emulsions as oral dosage form

Advantages
 Unpalatable drugs can be administered in palatable form
 Unpalatable oil-soluble drugs can be administered in palatable form
 Aqueous phase easily flavored
 Oily sensation easily removed

 Increased rate of absorption

  Possible to include two incompatible ingredients, one in each phase of
the emulsion

Disadvantages
 Preparation needs to be shaken well before use
 Measuring device needed for administration
 Need a degree of technical accuracy to measure a dose
 Storage conditions may affect stability
 Bulky, difficult to transport and prone to container breakages
 Liable to microbial contamination which can lead to cracking

Work out question

What quantities would be required to produce 100 mL of a 20% emulsion of a
fixed oil?
Answear
 For a 20% emulsion 20mL of the oil in 100mL of emulsion would be
required. Therefore 4 parts would be equivalent to 20mL of oil.
 Therefore 2 parts would be equivalent to 10mL aqueous phase.
 Therefore 1 part would be equivalent to 5 g of gum.

The formula for the primary emulsion would therefore be:

Fixed oil 20 mL
Aqueous phase 10 mL
Gum 5 g