PRINCIPLES OF COMPOUNDING

Terrick AndeyCollege of Pharmacy & Pharmaceutical

Sciences

Florida A&M University

February 2013

EMULSIONS

Definition: a two-phase dispersion in which one liquid is dispersed in the form of small droplets throughout another liquid

Characteristics: Dispersed liquid=internal or discontinuous phaseDispersion liquid=external or continuous phase

Types:Oil-in-water (o/w): dispersed phase=oil;

continuous phase-waterWater-in-oil (w/o): dispersed phase=water

continuous phase-oil

EMULSIONS

Emulsifying agent: facilitates the mixing of two immiscible liquids

Therefore, an emulsion consists of:Dispersed phaseDispersion mediumEmulsifying agent

EMULSIONS

Emulsifying agents: MOA: concentrate at and are absorbed onto the

oil:water interface to provide a protective barrier around the droplet

Stabilize the emulsion by reducing the interfacial tension of the system

Imparting a charge on droplet surface, reducing physical contact between droplets, and decreasing potential for coalescence

EMULSIFYING AGENTS Types of emulsifying agents:

Synthetic:Surfactants: move to a liquid-liquid interface; reduce surface/interfacial

tension of systemHave hydrophilic and lipophilic portions

Hydrophilic part: amino, hydroxyl, carboxyl Lipophilic part: alkyl chain

Classes of surfactants:Anionic: alkali soaps, amine soaps, detergentsCationic: benzalkonium chlorideNonionic: sorbitan esters, glyceryl esters

Natural: derived from plant or animal sourcesForm hydrated lypophilic colloid (hydrocolloid)No effect on interfacial tensionProtective colloid effect; reduces potential for coalescence

EMULSIFYING AGENTS

Hydrocolloid classification:Vegetable derivatives (o/w):acacia, tragacanth, agar,

pectin carrageenanAnimal derivatives (w/o): gelatin, lanolin,

cholesterol, lecithinSemi-synthetic agents (o/w):methylcellulose,

carboxymethylcelluloseSynthetic agents (o/w): carbopols

EMULSIFYING AGENTSFinely divided solids:

Form particulate layer around the dispersed particleSwells in the dispersion medium to increase viscosity and reduce

interaction between dispersed dropletsUsed as either o/w or w/o emulsifying agentsExamples: bentonite, Veegum®, magnesium hydroxide, aluminium

hydroxide, magnesium trisilicateAuxiliary agents:

Weak emulsifying properties; used in conjunction with other emulsifying agents

Stabilize emulsion by thickening the formulation Examples: fatty acids (stearic acid), fatty alcohols (steryl or cetyl

alcohol), fatty esters (glycerin monostearate)

EMULSIONS

Uses: In oral formulations

As vehicle for lipophilic drugs (o/w)To mask bitter taste of drugTo increase oral solubilityTo increase bioavailability

As lotions: fluid emulsions for external applicationAs creams: opaque, soft solids, or thick liquids for

external application; consists of agents dissolved/suspended in an emollient bases

HYDROPHILE-LIPOPHILE BALANCE

Hydrophile-Lipophile Balance (HLB):HLB helps in selecting the appropriate emulsifying

agent based on the balance between the hydrophilic and lipophilic portions of the emulsifying agent

Has a scale from 1-18Low HLB few hydrophlic groups on molecule

will have more of a lipophilic characterHigh HLB many hydrophlic groups on molecule

will have more of a hydrophlic character

EMULSIONS – HLBHLB USE

1-3 Antifoaming agents

3-8 Emulsifying agents for w/o emulsion

7-9 Wetting agents

8-16 Emulsifyinng agents for o/w emulsions

13-16 Detergents

15-20 Solubilizing agents

EMULSIONS - Preparation

Methods of preparation:Continental (Dry Gum or 4:2:1) MethodEnglish (Wet Gum) MethodBottle (Forbes) MethodBeaker MethodAuxiliary Methods

EMULSIONS - Preparation

Continental (Dry Gum or 4:2:1) Method In a dry mortar, the 1 part of emulsifier is triturate with the 4

parts oil until powder is wetted thoroughly Two (2) parts of water are added all at once, mixture is

vigorously and continuously triturated Creamy white primary emulsion forms

Primary emulsion formation is evident by crackling sound during trituration

NB: Trituration is done vigorously in one direction only

EMULSIONS - Preparation

Continental (Dry Gum or 4:2:1) Method Form primary emulsion from 4 parts of oil, 2 parts of

water, and 1 part of emulsifier Example: Mineral Oil Emulsion U.S.P.

Mineral Oil Emulsion U.S.P.Rx Mineral Oil 500 ml acacia, fine powder 125 gm Syrup 100 ml Vanillin 40 mg alcohol 60 ml Purified water, q.s. ad. 1000 ml

Procedure:Mix mineral oil and acacia in a dry Wedgwood/porcelain mortarAdd 250 ml water and triturate the mixture vigorously until an emulsion is formedDissolve syrup, vanillin, and 50 ml of purified water in alcohol in small portions whilst trituratingAdd sufficient purified water to make 1L

EMULSIONS - Preparation English (Wet Gum) Method

Proportion of oil, water and emulsifier can be the same (4:2:1) However, order of mixing is different Triturate 1 part of emulsifier with 2 parts of water to form wetted

mixture Add slowly in small portions, the 4 parts of oil while triturating After all oil is added, triturate mixture for several minutes to form

primary emulsion Light rapid trituration in one direction is needed for a good

emulsion

EMULSIONS - Preparation Bottle (Forbes) Method

A variation of dry gum method Used to prepare emulsions of volatile oils or oleaginous substances of very

low viscosities Not suitable for highly viscous oils; they cannot be agitated sufficiently in a

bottle Procedure: Place acacia (1 part) in bottle and add 4 parts of oil Cap bottle and thoroughly shake rapidly with short strokes Add required amount of water all at one Shake mixture thoroughly until primary emulsion is formed

EMULSIONS - Preparation

Beaker MethodFirst three methods use hydrocolloid (gum)

emulsifiers which are not suitable when using non-gum or synthetic emulsifiers

Not also the method of choice for compounding lotions or creams

The Beaker method is thus preferred is these cases

EMULSIONS - Preparation Beaker Method

All ingredients are divided into water-soluble and oil-soluble groups

Water-soluble ingredients are dissolved in one beaker Oil-soluble ingredients are dissolved in a separate beaker Both beaker are heated to about 70°C using a low-temperature

hot plate or steam bath NB: Aqueous phase is heated a few degrees higher than

oleaginous phase, since aqueous phase will cool faster The two beakers are removed from source of heat and the

internal phase is slowly added to the external phase while stirring continuously

Produce is allowed to cool to room temperature while stirring

EMULSIONS - Uses

As ointment bases: o/w ointment base: water miscible; non-occlusive; non-

greasy Examples: Vanishing cream (stearic acid cream), Hydrophilic

ointment, Weobase, Onibase, Multibase, Dermabase. w/o ointment base: water immiscible; non-water-

washable; non-water-absorbable; occlusive, greasy (typically) Examples: Rose water ointment (Cold cream U.S.P.), Hydrous wool

fat (Lanolin)

EMULSIONS - Uses

Hydrophilic Ointment U.S.P.Rx

Methylparaben 0.25 gmPropylparaben 0.15 gmSteryl alcohol 250 gmWhite petrolatum 250 gmPropylene glycol 120 gmsodium lauryl sulfate 10 gmPurified water 370 gm

1000 gm

PROCEDURE:Melt steryl alcohol and white petrolatum on a steam bath up to 75°CSeparately warm Purified water, mixed with methylparaben, propylene glycol, propylparaben, and dissolve sodium lauryl sulfate to dissolveWith both contents dissolved at 75°C, mix the two and stir until the mixture (emulsion) is completely congealed

EMULSIONS - Uses

Rose water ointment (Cold cream U.S.P.)

RxCetyl Esters Wax 125 gmWhite Wax 120 gmAlmond Oil 560 gmSodium Borate 5gmStronger Rose Water 25 glPurified Water 165 mlRose Oil 0.2 ml To make about 1000 gm

PROCEDURE:Triturate cetyl esters wax and the white wax, melt them on a steam bathAdd the almond oil and continue heating until the temperature of the mixture reaches 70°CDissolve the sodium borate in the purified water and stronger rose water, water to 70°CGradually add the warm solution to the melted mixture, stirring rapidly and continuously until it has cooled to about 45°CIncorporate the rose oil.