SCHOOL OF PHARMACY

Subject: PHARMACY PRACTICE 1

Subject code: SPH1023

Assignment: COMPOUNDING TOPICAL DOSAGE FORMS

Prepared by : ANNISA HAYATUNNUFUS (012014052438)

Lecturer’s Name : SIR NIZAM GHANI

Date of submission : 12th MARCH, 2015

TABLE OF CONTENT

I. Table of Content.....................................................................2

II. Introduction............................................................................3

III. Discussions..........................................................................7

A. Ointment........................................................................7

1. General Procedure................................................7

2. Problems & How to Overcome Them....................8

3. Additives................................................................9

B. Cream.........................................................................10

1. General Procedure..............................................10

2. Problems & How to Overcome Them..................10

3. Additives..............................................................11

C. Lotion..........................................................................11

1. General Procedure..............................................11

2. Problems & How to Overcome Them..................12

3. Additives..............................................................12

IV. References.........................................................................14

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I. INTRODUCTION

In extemporaneous compounding, it is important to consider which dosage

form suits the patient best. If a wrong or unsuitable dosage form was sent, the

drug may not be distributed properly to the site of action and become

therapeutically ineffective, or in worst case—it may not be safe and subsequently

worsen the patient’s condition.

The dosage form itself may vary according to the drug’s functions and the

patient’s needs. It may correlate with the complexity of the administration route,

the location of site of action, or the patient’s needs such as ability to swallow, skin

sensitivity, and others.

The type of dosage form that is going to be discussed here is the dosage

form for the topical route of administration. ‘Topical’ refers to a type of medication

that is applied directly to the skin, as opposed to being taken by mouth. (Topical

medications can also be put in the eye or ear). Three examples of this dosage

form are lotion, cream, and ointment.

Ointments, creams, and lotions are different ways to formulate over-the-

counter products or medicines. An ointment is 80% oil and 20% water. A cream is

50% oil and 50% water. A lotion is similar to a cream, but it is an even lighter or

less thick formulation. Any of these can be used with different over-the-counter

products or drugs, depending on the dryness or oiliness of one’s skin.

Lotions are similar to solutions but are thicker and tend to be

more emollient in nature. They are usually oil mixed with water, and more often

than not have less alcohol than solutions. Lotions can be drying if they contain a

high amount of alcohol. There is a significant variability in the ingredients of base

of generic lotions when compared to brand name lotions.

Lotion is commonly applicated to inflamed ulcerated skin and is able to cool

the skin by evaporation of solvents. They absorb very quickly and feel very light

on the skin. They are easier to distribute on hairy areas. Most over-the-counter

body moisturizers are lotions, where they are often packaged in a pump.

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Cream is semisolid emulsion of oil and water with equal proportions. It

contains an emulsifying base and is used for external use, penetrating

the stratum corneum outer layer of skin well. Cream is thicker than lotion, and

maintains its shape when removed from its container. It tends to be moderate in

moisturizing tendency as it reasonably hydrates without feeling too heavy on the

skin. It has a high rate of acceptance by patients. There is a great variation in

ingredients, composition, pH, and tolerance among generic brands.

Two main types of cream are oil in water (o/w) cream and water in oil (w/o)

cream. o/w cream is more comfortable and cosmetically acceptable as they are

less greasy and more easily water washable. o/w creams that are readily rub into

the skin are termed as vanishing cream. Meanwhile, w/o creams accommodate

and release better lipophilic API. They are also more commonly used for topical

steroid products.

Creams are always packaged in a tub or a tube; they are too thick to be

dispensed in a pump. Creams for external use are stored in wide-mouth jars with

lid. The mouth of the jar should be covered with a disc of greaseproof paper.

Collapsible metal or plastic tubes are sometimes preferred for cream as these

reduce the risk or contamination.

Creams are often used to treat acne in patients whose skin is somewhat

dry, as the creams promote hydration. Creams are also more beneficial in darker

skin, which in general is more easily irritated than lighter skin.

An ointment is a homogeneous, viscous, semi-solid preparation, most

commonly a greasy, thick oil (oil 80% - water 20%) with a high viscosity, that is

intended for external application on a variety of body surfaces. These include

the skin and the mucous membranes of the eye (an eye ointment), chest, vulva,

anus, and nose.

Ointments are ‘occlusive,’ which means they trap moisture and heat in very

well and good for dry skin. They have a low risk of sensitization due to having few

ingredients beyond the base oil or fat, and low irritation risk. Ointments promote

medication absorption over all other formulations. If an ingredient is in an

ointment, it is always more potent than the exact same ingredient packaged in a

cream or lotion.

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A medicament would usually be incorporated in the ointment. Sometimes it

can also contain a mixture of medicaments that is dissolved or dispersed in the

base. Ointment bases may be divided into oligeanous (hydrocarbon), absorptive,

water-miscible, and hydrophilic. The choice of a base depends upon the clinical

indication for the ointment.

1. Hydrocarbon bases

Hydrocarbon bases are immiscible with water and are not absorbed

by the skin. They usually consist of soft paraffin or mixtures of soft paraffin

with hard paraffin or liquid paraffin. There would be a greasy waterproof film

on the skin that is formed by the paraffin. This would stop water loss from

the skin, hence would improve the skin hydration. This is particularly

important in the treatment of dry scaly medical conditions such as psoriasis.

Examples of this base are hard paraffin, soft paraffin, microcrystalline

wax and ceresine.

2. Absorption bases

These bases can act as good emollients and are less occlusive. It is

easier to apply than hydrocarbon bases. Absorption bases can be divided

into non-emulsified bases and water-in-oil emulsions.

Non-emulsified bases are bases that absorb water to form water-in-oil

emulsions. They consist of a hydrocarbon base combined with a water-in-oil

emulsifier such as Wool Acohols BP or Wool fat BP. Water-in-oil emulsions

are similar to non-emulsified bases but are capable of absorbing more

water. The components of emulsified bases include Hydrous Wool Fat BP

and Oily Cream BP.

3. Water-miscible/emulsifying bases

These are anhydrous bases that contain oil-in-water emulsifying

agents, which make them miscible in water and therefore washable and

easily removed after use. There are three emulsifying ointments that are

used as water-miscible bases which are emulsifying ointment BP, cetrimide

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emulsifying ointment BP, and cetomacrogol emulsifying ointment BP. Since

the bases mix readily with the aqueous secretions of the skin, it makes the

ointment to be easily washed out. So they are particularly suitable for use

on the scalp. Examples of this base are emulsifying wax and cetrimide

4. Hydrophilic bases

Hydrophilic bases are developed from polyethylene glycols

(macrogols). They mix readily with skin secretions and are non-occlusive.

These bases are also easily removed upon washing. Macrogol bases are

commonly used with local anesthetics such as Lidocaine BP.

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II. DISCUSSIONS

A. OINTMENT

1. General Procedure

In general, there are two methods of preparation in making an

ointment: the fusion method and trituration method.

Fusion method usually involves the compounding of many semisolid

preparations that may be hard to blend with each other such as oily

materials. Some materials are even solid at room temperature and

available in a size too large than what is needed. Therefore, fusion

method will make it easier to blend by melting it first.

Meanwhile, trituration method involves insoluble solids or liquids,

which are incorporated into the bases. The kind of solid that is suitable for

the trituration method is a coarse powder because it easy to be decreased

in size into a fine powder. More detailed procedures of the trituration &

fusion methods are as stated below:

Trituration: With this method, finely subdivided insoluble medicaments

are evenly distributed by grinding with a small amount of the base,

followed by dilution with gradually increasing amounts of the base.

a) To avoid grittiness, powders should be passed through a 180µm

sieve before weighing.

b) This method is done on a glazed porcelain or glass ointment slab

or tile. A flexible spatula is used to mix the material together.

c) Powders are placed on the tile and using doubling-up technique,

the powders are incorporated into the base. In order to avoid

‘crumbling’, it is necessary to have two or three times the volume

of base to powder.

d) If a liquid is present, it is often present in small amounts. To

incorporate a liquid, a portion of the base is placed on the slab and

a recess made to hold the liquid. Then, mix well the liquid and the

base.

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e) If we are dealing with a large quantity, then using the same

method, the liquid is added little at a time.

f) Theoretically, it is possible to recover all material from the slab but

it is normal to allow up to 10% excess for losses. Using a mortar

with a flat base and a pestle with a flat head, this process can be

carried out.

Fusion: In this method, the ingredients are melted together in

descending order of their melting points. Then they are stirred to

ensure homogeneity.

a) This method is done in an evaporating dish on a water-bath or hot

plate.

b) High temperature is not required; 60-70ºC is adequate.

c) Waxy solids must first be grated before weighed. Then it should be

added first, so the melting can start whilst other ingredients are

being prepared.

d) The basin from the water-bath is removed when all the ingredients

are melted. It is then stirred until cold.

e) In order to avoid bubbles and formation of lumps, the mixing

should be done gently.

f) Medicaments may be added at different stages of the preparation

depending on its properties. A soluble and stable medicament can

be added when the base is molten. A less stable or insoluble but

easy to disperse can be added during cooling. However, if it is

unstable and difficult to disperse, it should then be added when it

is cold—using mixing by trituration.

g) It is important to make an excess of about 10% because when

evaporating basins are being used, the recovery of the entire

product is not possible.

2. Problems & How to Overcome Them

The primary indication of instability for semisolid topical dosage forms

is either discoloration or a noticeable change in consistency or odor.

Specifically for ointment, the common signs of instability are changes

in particle size, hydration state, consistency, and drug release rate. In

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such case, one of the ways to prevent those instabilities is to design the

product based on proper pre-formulation studies.

Sometimes, excessive ‘bleeding’ (i.e., separation of excessive

amounts of liquid) and formation of granules or grittiness (caking or

coalescence) will occur. Accurate preparation of ointment may reduce this

problem.

Also, some people may develop a hypersensitivity reactions to

ointments that are given to them. This is due to the presence of some

minor impurities. Other times, this problem also arises when a patient has

an allergy to a certain ingredient used in the dosage form. That is why

other dosage form may also develop the same problem.

In dealing with this hypersensitivity reaction problem, combinations of

bases are sometimes used to acquire better stability.

3. Additives

Ingredients UsageHydrocarbons / Vegetable

Oils / Animal Fat /

Hydrogenated and

Sulphated Oils / Alcohols,

Acids, Esters / Silicones

Oleaginous Bases

Fragrant oils To add fragrance if necessary

Vitamin E oil / Rosemary

Frond ExtractAntioxidants

Bithional / Ethyl Paraben /

Sorbic AcidPreservatives

Citric Acid / Maleic Acid /

Phosphoric AcidChelating Agent

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B. CREAM

1. General Procedure

The pharmacist may be asked to prepare extemporaneous dilutions of

proprietary creams. Dilutions should be carried out only if the diluent to be

used is the stated in the manufacturer’s data sheet (this is usually quoted

in the BNF). The creams must be freshly prepared without heat and with

strict hygienic precaution. Meanwhile, the following is the general

procedure to make a cream from the basic ingredients:

a. Creams are prepared by heating the components of the oily phase

(including the emulsifying agents) until molten at 60 – 70ºC.

b. The components of aqueous phase are mixed separately and also

heated to 60 – 70ºC.

c. The aqueous mixture is then poured into the oily phase at the same

temperature. The resultant mixture is then stirred until cool.

2. Problems & How to Overcome Them

One of the main concerns of using cream dosage form is that it is

prone to lose water, especially in the oil/water type. The more water that

are lost, the easier it is for cream to become dry and ultimately shrinks

due to evaporation or come in contact with too much acid. This problem

can be dealt with proper storage such as making sure that the lid was

properly closed or keeping the cream in a controlled room temperature.

Aside from that, creams also have the problems of emulsion

breakage, crystal growth, and gross microbial contamination. Especially

for the case of microbial contamination, it can be prevented by using a

suitable quality of raw materials, good manufacturing practices, adequate

preservation, and the use of noninvasive packages (such as tubes,

pumps, or narrow orifice containers).

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3. Additives

Ingredients UsageWool Fat / Waxes /

Bivalent Soaps / Sorbitan

Esters / Wool Alcohol

Emulsifying agent for w/o creams

Polysorbates / Methyl

Cellulose / Monovalent

soap / Acacia / Tragacanth

/ Triethanolamine Oleate

Emulsifying agent for o/w creams

Cocoamide Dea /

Propylene Glycol / Sodium

Lauryl Sulfate / Sodium

Lauryl Fluoride

Add scent if necessary

Organic Acids / Esters of

Parahydroxybenzoid Acid /

Chlorocresol /

Phenoxyethanol /

Quaternary Ammonium

Compounds / Organic

Mercurial Compounds

Preservatives (same as lotion’s)

C. LOTION

1. General Procedure

The following procedure is an example of the compounding of

Calamine Lotion, therefore some points or ingredients added may only be

valid to this particular lotion. The procedure is as follow:

a. Weigh all ingredients accurately

b. Transfer the weighed bentonite (suspending agent) to the mortar

c. Add the zinc oxide (active ingredient with antiseptic properties)

using the doubling-up technique, then triturate with pestle

d. Add calamine powder (active ingredient for itching & irritation)

using doubling-up technique, then triturate with pestle

e. Add sodium citrate (pH buffer/chelating agent/antioxidant) to the

mortar, mix with pestle to form a smooth paste

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f. Add glycerol (for humectant effect) & liquefied phenol (for cooling

effect) to the paste, mix with pestle until the mixture is pourable

g. Transfer the contents to a conical measure or the final container

h. Rinse the mortar with water and add to the final container

i. Make up to volume with any remaining water

j. Label appropriately and dispense

2. Problems & How to Overcome Them

Certain lotions tend to separate or stratify on long standing. In such

case, they require a label directing that they should be shaken well before

each use. This will help mixing the lotion again so that the ingredient is

spread evenly.

Just like other dosage form, microorganisms may grow in lotions if no

preservative is included. However, a lotion that are microorganism-free

might still be contaminated after usage. Therefore, extra care should be

taken to avoid contaminating the lotion during preparation, even if a

preservative is present.

3. Additives

Ingredients UsageWater Decrease greasiness

Bentonite Suspending agent

Methyl Cellulose/Sodium

Carboxymethyl Cellulose

Holds active ingredient in contact with the

affected site & at the same time rinsed off

easily with water.

AlcoholAccentuate drying & cooling effect of a

lotion

Glycerin Gives a humectant (moisture preservative)

effect

Sodium Citrate pH buffer/chelating agent/antioxidant

Organic Acids / Esters of

Parahydroxybenzoid Acid /

Chlorocresol /

Phenoxyethanol /

Quaternary Ammonium

Preservatives (same as cream’s)

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Compounds / Organic

Mercurial Compounds

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III. DISCUSSIONS

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Premjeet, S., Ajay, B., Sunil, K., Bhawana, K., Sahil, K., Divashish, R., &

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and Application to Pharmacy Practice. United States: Academic Press.

Hunt, Desmond G (1991). Stability Considerations in Dispending Practice.

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Okeke, I.N. and Lamikanra, A. (2001), Bacteriological quality of skin-

moisturizing creams and lotions distributed in a tropical developing country.

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Journal of Applied Microbiology, 91: 922–928. doi: 10.1046/j.1365-

2672.2001.01456.x

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