PRINCIPLES OF COMPOUNDING Terrick Andey College 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 phase Dispersion liquid=external or continuous phase Types: Oil-in-water (o/w): dispersed phase=oil; continuous phase-water Water-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 phase Dispersion medium Emulsifying 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 system Have hydrophilic and lipophilic portions Hydrophilic part: amino, hydroxyl, carboxyl Lipophilic part: alkyl chain Classes of surfactants: Anionic: alkali soaps, amine soaps, detergents Cationic: benzalkonium chloride Nonionic: sorbitan esters, glyceryl esters Natural: derived from plant or animal sources Form hydrated lypophilic colloid (hydrocolloid) No effect on interfacial tension Protective colloid effect; reduces potential for coalescence

EMULSIFYING AGENTS Hydrocolloid classification: Vegetable derivatives (o/w):acacia, tragacanth, agar, pectin carrageenan Animal derivatives (w/o): gelatin, lanolin, cholesterol, lecithin Semi-synthetic agents (o/w):methylcellulose, carboxymethylcellulose Synthetic agents (o/w): carbopols

EMULSIFYING AGENTS Finely divided solids: Auxiliary agents: Form particulate layer around the dispersed particle Swells in the dispersion medium to increase viscosity and reduce interaction between dispersed droplets Used as either o/w or w/o emulsifying agents Examples: bentonite, Veegum®, magnesium hydroxide, aluminium hydroxide, magnesium trisilicate Auxiliary 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 drug To increase oral solubility To increase bioavailability As lotions: fluid emulsions for external application As 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 1-18 Low HLB few hydrophlic groups on molecule will have more of a lipophilic character High HLB many hydrophlic groups on molecule will have more of a hydrophlic character

EMULSIONS – HLB HLB 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) Method English (Wet Gum) Method Bottle (Forbes) Method Beaker Method Auxiliary 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 mortar Add 250 ml water and triturate the mixture vigorously until an emulsion is formed Dissolve syrup, vanillin, and 50 ml of purified water in alcohol in small portions whilst triturating Add 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 Method First 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 gm Propylparaben 0.15 gm Steryl alcohol 250 gm White petrolatum 250 gm Propylene glycol 120 gm sodium lauryl sulfate 10 gm Purified water 370 gm 1000 gm PROCEDURE: Melt steryl alcohol and white petrolatum on a steam bath up to 75°C Separately warm Purified water, mixed with methylparaben, propylene glycol, propylparaben, and dissolve sodium lauryl sulfate to dissolve With 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.) Rx Cetyl Esters Wax 125 gm White Wax 120 gm Almond Oil 560 gm Sodium Borate 5gm Stronger Rose Water 25 gl Purified Water 165 ml Rose Oil 0.2 ml To make about 1000 gm PROCEDURE: Triturate cetyl esters wax and the white wax, melt them on a steam bath Add the almond oil and continue heating until the temperature of the mixture reaches 70°C Dissolve the sodium borate in the purified water and stronger rose water, water to 70°C Gradually add the warm solution to the melted mixture, stirring rapidly and continuously until it has cooled to about 45°C Incorporate the rose oil.