MANUFACTURE OF CREAMS

IV Pharm D
Hospital Pharmacy
 DEFINITION
 Creams are homogenous, semi-solid or viscous preparations that possess

a relatively fluid consistency and are intended for external application to

the skin or certain mucous membranes for protective, therapeutic or
prophylactic purposes.

 They usually contain a water soluble base due to which they can be

easily removed from the skin.

 They are softer and light weight in comparison to ointments when

applied to skin.
 ADVANTAGES
 Convenient and easy to apply.
 When applied to the skin, they produce emollient and soothing effect.
 They are less viscous and easily spread to the skin.
 Addition of emulsifier, improve the drug penetration.

DISADVANTAGES
 Creams are not suitable for prolonged effect as they are less viscous
and easily washable.
 Due to high moisture content, they require additional preservative for
their stability.
 Creams are not suitable for open wounds due to their high surfactant
content and are non-sterile.
 Possibility of skin irritation and allergic reactions.
 IDEAL PROPERTIES OF CREAMS

 They should be stable and have a good appearance.

 They should melt or soften on application to the skin.

 They should spread easily.

 A light emollient film should remain on the skin.

 They should be non-irritant.

 FORMULATION OF CREAMS

Bases used in cream

Base type Characteristics Uses Examples

Hydrocarbon Insoluble in water Protectant White petrolatum
(Oleaginous) Anhydrous Emollient White ointment
bases Emollient Vehicle for drugs
Greasy prone to hydrolysis.
Poor drug release
Will not absorb water
W/O Insoluble in water Emollient Hydrous lanolin
emulsion Not water washable Cleansing cream Cold cream
base Emollient Vehicle for liquids Rose water
Greasy and solids ointment
Fair to good drug release
Base type Characteristics Uses Examples

o/w emulsion Water washable Emollient Vanishing cream

base (water- Can absorb water Hydrophilic
removable) Non-greasy ointment
Fair to good drug
release

Water soluble Water soluble Emollient Polyethylene glycol

Water washable Vehicle for liquids,
Absorbs water solids
Non-greasy Local anaesthetic
Drug release good
Adjuvants used in creams

 Antioxidants: Ascorbic acid

 Buffer: Citrate buffer, phosphate buffer

 Chelating agents: EDTA, Citric acid

 Emulsifying agent: Detergent, cetostearyl alcohol

 Humectant: Glycerin, propylene glycol, Polyethylene glycol

 Permeation enhancer: Ethanol, oleic acid, PEG

 Preservative: Benzoic acid, phenyl ethyl alcohol

 Thickening agent: Cellulose, pectin

 Perfume: Lavender oil, rose oil, lemon oil.

 GENERAL METHOD OF PREPARATION OF CREAMS

 All ingredients can be divided into oil phase and aqueous phase.

 Ingredients of oil phase should be taken in increasing order of their

melting point.

 Take separately the ingredients of aqueous phase, mix and heat to the

same temperature as oily phase.

 Mix the two phases with continuous stirring until a smooth cream is

formed.

 Perfume should be added after the primary cream.

 METHODS OF PREPARATION
(1) Trituration
(2) Levigation
(3) Fusion
(4) Mechanical addition

(1) Trituration
 Used for finely divided insoluble powder particles or liquids.
 Insoluble powders are added by geometric dilution.
 Liquids are added by making a well in centre.
 Air pocket formation avoided.
 A glass slab used in case of small quantities.
 Mortar and pestle is used in case of large quantities.
(2) Levigation
 Incorporation of insoluble coarse particles
 Also known as wet grinding as insoluble coarse powder is rubbed with
molten base or liquid or a semi-solid base.

(3) Fusion
 Fusion method is used when the drugs and other solid are soluble in
ointment bases.
 The base is liquefied and the soluble components are dissolved in the
molten base.
 The mixture is then triturated to obtain a smooth texture.
 Care is taken to avoid thermal degradation of the base or other
components during the fusion process.
(4) Mechanical addition

 Used for hydrophilic creams.

 Water removable creams are hydrophilic type emulsions.

 A hydrophilic emulsifying agent is included in the aqueous phase in

order to obtain a stable o/w emulsion.

 Sodium lauryl sulphate is used in the preparation of hydrophilic creams.

 A wide range of machines are available for the large scale production of

creams

 Creams are produced with the help of low-shear and high emulsifiers.
 TYPES OF CREAMS
Creams are of two types:
(1) Aqueous creams
(2) Oily Creams

(1) Aqueous creams

 In aqueous creams, the emulsions are o/w type.
 They are non-greasy.
 They are further divided into three types depending on the type of
emulsifying agent used for them.

(a) Anionic emulsifying wax creams

 These creams are prepared by fusion method.
 The wax and oily ingredients are melted together and cooled to about
600C.
 The water or aqueous solution is warmed to the same temperature as
oily mixture with constant stirring until cold.
Example: Preparation of 100 g of Calamine cream B.P.C.

Ingredients:
Calamine 4g
Zinc oxide 3g
Emulsifying wax 6g
Arachis oil 40 g
Water 47 g

Method: Melt the emulsifying with gentle heat. Add arachis oil and warm.
Add water at the same temperature, stir until cold. Triturate the calamine
and the zinc oxide with water and incorporate in the cream. Transfer the
cream in a suitable container, label and dispense.
(b) Cationic emulsifying wax creams
 These are prepared in the same way as that of anionic emulsifying cream
(fusion method).

Example: Preparation of 100 g of cetrimide cream B.P.

Ingredients:
Cetrimide 0.5 g
Cetostearyl alcohol 5g
Liquid paraffin 50 g
Purified water 44.5 g

Method: Melt the cetostearyl alcohol on a water bath. Add the liquid
paraffin and heat to 600C. Dissolve cetrimide in a freshly boiled and cooled
purified water and warm to 600C. Add the aqueous solution to the oily
mixture and stir until cold. Transfer the cream into a suitable container,
label and dispense.
(c) Non-ionic emulsifying wax creams
 These are also prepared by fusion method.

Example: Preparation of 100 g of hydrocortisone cream B.P.C.

Ingredients:
Hydrocortisone acetate 1g
Cetomacrogol emulsifying ointment 30 g
Chlorocresol 0.1 g
Purified water 68.9 g

Method: Dissolve the chlorocresol in the purified water with gentle heat.
Melt the Cetomacrogol emulsifying ointment on a water bath, add the
chlorocresol solution at the same temperature, stir until cold and
incorporate the hydrocortisone acetate. Transfer to a suitable container,
label and dispense.
*Vanishing Cream
 These are o/w type emulsion with stearic acid as the emulsifying agent.
 When applied on the skin, the spread as thin oil less film which is not
visible to the naked eye. Hence, they are called vanishing creams.

Preparation of 100 g of vanishing cream B.P.C

Ingredients:
Stearic acid 23.5g
Cetyl alcohol 0.5 g
Potassium hydroxide 1g
Glycerin 10.5 g
Water 64 g
Perfume 0.5 g

Method: Melt stearic acid and cetyl alcohol at 750C. Dissolve KOH in
purified water heat to the same temperature as above. Add glycerin,
perfume to the mixture and stir until cold.
(b) Oily creams
 In oily creams, emulsions are w/o type.
 They are further divided into types depending on the emulsifying agent
used.

(a) Sterol creams

 In this wool fat or wool alcohol is used as the emulsifying agent.

Example: Preparation of 100 g of proflavine cream B.P.C.

Ingredients:
Proflavine hemisulphate 0.1 g
Chlorocresol 0.1 g
Yellow beeswax 2.5 g
Wool fat 5.0 g
Purified water 25.0 g
Liquid paraffin 67.3 g
Method: Dissolve chlorocresol in 75% of the liquid paraffin in a covered
china dish using gentle heat. Melt the yellow beeswax and wool fat together
and heat to 700C. Add the chlorocresol solution. Dissolve the proflavine
hemisulphate in calculate quantity of water and heat to 700C. Add the
aqueous solution to oily mixture with constant stirring. Add the rest of
liquid paraffin and stir until cold. Transfer to a suitable container, label and
dispense.

(b) Soap creams

 These are w/o emulsions in which the emulsifying agents used are

triethanolamine soap, calcium soap or borax soap.

Example: Preparation of 100 g of barrier cream B.P.C.

Ingredients:
Hard paraffin 25.0 g
Soft paraffin 11.75 g
Liquid paraffin 3.5 g
Cetostearyl alcohol 5.0 g
Triethanolamine 0.7 g
Stearic acid 1.8 g
Chlorocresol 0.2 g
Purified water 52.05 g

Method: Melt together cetostearyl alcohol, stearic acid, hard paraffin and
soft paraffin. Add liquid paraffin and heat to 700C. Dissolve the
triethanolamine in chlorocresol solution and heat to 700C. Add the aqueous
solution to oily mixture with constant stirring until cold. Transfer to a
suitable container, label and dispense.
*Cold cream
 It’s a w/o type emulsion.
 The name derives from the cool feeling that the cream leaves on the skin
due to the slow evaporation of water present in the emulsion.

Preparation of 100 g of cold cream B.P.C.

Ingredients:
White beeswax 20 g
Liquid paraffin 60 g
Borax 1.0 g
Water 19 g

Method: Melt the white beeswax with liquid paraffin and heat upto 700C.
Dissolve the borax in water and heat the solution to 700C. Gradually add the
solution to the melted mixture and stir until cold. Transfer to a well-closed
container, label and dispense.
 EVALUATION OF CREAMS
 pH of the cream

 Viscosity

 Rheological property of the cream

 Determination of type of emulsion

- Dilution test
- Dye test
 Stability test

- Globule size
- Phase separation
- Moisture absorption studies
- Spreadability
pH of the cream
 Determined by using a digital pH meter.

 1 g of the cream is dissolved in 100 ml of distilled water and stored for

two hours.
 The measurement is done in triplicate and average values are
calculated.

Viscosity
 Determined by Brookfield Viscometer.

 Carried out at 20 rpm at a temperature of 250C and the measurement

is done in triplicate and average of three readings are recorded.
Rheological property of the cream

 Determined to know the flow behaviour of the cream.

 The viscosity at different rpms are measured and the rheological

property is studied by taking 100 g of the cream in the beaker.

 The rate of shear is increased from minimum to maximum and

corresponding values are noted.

 The rate of shear is then decreased gradually to the lowest value and

the reading is recorded.

 The graph is plotted between percent torque and viscosity to determine

type of flow.
Determination of the type of emulsion
(1)Dye test

 Water soluble dye dissolves in the aqueous phase (o/w)

 Oil soluble dye dissolves in the oil phase (w/o)

(2) Dilution Test

 Based on the solubility of external phase of emulsion.

 Add few drops of water into the emulsion. If the water distributes

uniformly, then it is o/w emulsion. And if the water separate out as a

layer, then it is w/o emulsion.
Stability test

Globule size:

 1 ml of cream is diluted to 10 ml with glycerin.

 A few drops of this is transferred to a glass slide and focused in a

microscope and determine the size of globule.

Phase separation:

 The cream is kept intact in the closed container at 25-300C not exposed

to light

 Phase separation is observed carefully every 24 hours for 30 days

Moisture absorption studies:
 50 mg of cream is taken in a watch glass.
 A beaker was taken with full of water and was kept in a desiccator
without adsorbents.
 Watch glass with cream was introduced into the desiccator and left for
24 hrs.
 After 24 hours check the level of water in the beaker

Spreadability:
 It is expressed in terms of time in seconds.

 Take two slides to slip off from the cream, placed in between the slides,
under certain load.
 Lesser the time taken for the separation of the two slides, better the
spreadability
 CONTAINERS
 Creams should be stores in wide mouthed squat jars.
 The mouth of jar should be covered with a disc of grease proof paper.
 The containers must be well closed to prevent evaporation of water.
 When issued for use, creams should be supplied in collapsible tubes.

LABELLING
Secondary labels such as ‘For external use only’ and ‘ Store in a cool place’
should be fixed on the container.

STORAGE
The creams should be stored in a cool place with temperature not exceeding
250C. Creams should be protected from higher temperature and direct
sunlight.