Dodecane droplets in a continuous phase of water/glycerol mixture. Sodas: Oil in Water emulsionMilk: Oil in Water emulsionBalm: Water in oil emulsion Mayonnaise: Oil in Water emulsionEmulsionsEmulsion suitable for intravenous injection.

Emulsion Dispersion of liquid droplets (dispersed phase) of certain size within a second immiscible liquid (continuous phase).Classification of emulsions- Based on dispersed phase Oil in Water (O/W): Oil droplets dispersed in water Water in Oil (W/O): Water droplets dispersed in oil Water in Oil in water (W/O/W): Water in Oil emulsion dispersed in water multiple emulsion- Based on size of liquid droplets0.2 50 mm Macroemulsions0.01 0.2 mm Microemulsions

AdvantagesAdministration of Distasteful oil, mask the unpleasant tasteBetter and faster absorptionLess irritation to the skinSustained release medicationNutritional supplementDiagnostic purposes

Emulsions encountered in everyday life! Stability of emulsions may be engineered to vary from seconds to years depending on application

Stable dispersions of liquids constituting the dispersed phase, in an immiscible liquid constituting the continuous phase is brought about using emulsifying agents such as

Carbohydrates: acacia, tragacanth, agar, chondrus and pectin

Proteins: gelatin, egg yolk and caseinHigh mol wt alcohols: stearyl alcohol, cetyl alcohol, glycery monostearate, cholesterol w/o stabilisersSurfactants: SPAN, TWEEN, organic soaps ( triethanolamine oleate),Non ionic- pH 3-10, cationic 3-7, anionic- greater than 8

Emulsifying Agents

SurfactantsAnionic Sodium stearate, Potassium laurateSodium dodecyl sulfate, Sodium sulfosuccinateNonionic Polyglycol, Fatty acid esters, LecithinCationic Quaternary ammonium salts, Finely divided SolidsFinely divided solids with amphiphilic properties such as silica and clay, may also act as emulsifying agentsOthers: bentonite, magnesium hydroxide, Al(OH)3

Common Emulsifying Agents

Based on the Bancrofts rule, many emulsion properties are governed by the properties of the continuous phase

Dye test Dilution testElectrical conductivity measurements 4. Filter paper testTests for Emulsion Type (W/O or O/W emulsions)

Thermodynamic instability G = . AIncrease in the surface free energy = interfacial tension X increased surface area

Mechanism of emulsification

Monomolecular theory SurfactantsReduce interfacial tensionForms a protective film around globuleIonic surfactant exert repulsion between globules

Mechanism Multimolecular theoryHydrocolloids form multimolecular physical barrier around globules there by prevent coalescence of oil globulesAcacia, gelatin Solid particle adsorption theory

Physical InstabilityCreaming: Concentration of globules at the top or bottom of emulsion.Reversible process but leads to breakingInfluenced by: Stokes equationV = h = d2st (so) g t 18o-globule size-Viscosity of dispersion medium-Difference in the densities of dispersed and dispersion medium

Droplets larger than 1 mm may settle preferentially to the top or the bottom under gravitational forces.Creaming is an instability but not as serious as coalescence or breaking of emulsionProbability of creaming can be reduced if

a - droplet radius, - density difference, g - gravitational constant, H - height of the vessel,

Creaming can be prevented by homogenization. Also by reducing , creaming may be prevented.

Creaming of Emulsions

Creaming can be reduced/prevented byReducing the globule size by homogenizationIncreasing the viscosity of dispersion mediumReducing the difference in densities

CoalescenceSeparation of two phases due to fusion of globules. Also called cracking of emulsion.Irreversible process.Sheath of EA around globules is lost.Creaming leads to breaking- globules comes nearerBreaking of emulsion is observed due to:Insufficient amount of EAIncompatibility between EAAlteration in the properties of EA

O/W W/O

The order of addition of the phasesW O + emulsifier W/OO W + emulsifier O/WNature of emulsifierMaking the emulsifier more oil soluble tends to produce a W/O emulsion and vice versa.Phase volume ratioOil/Water ratio W/O emulsion and vice versa

Inversion of Emulsions (Phase inversion)

4. Temperature of the systemTemperature of O/W (polyoxyethylenated nonionic surfactant) makes the emulsifier more hydrophobic and the emulsion may invert to W/O.

5. Addition of electrolytes and other additives.Strong electrolytes to O/W (stabilized by ionic surfactants) may invert to W/OExample. Inversion of O/W emulsion (stabilized by sodium cetyl sulfate and cholesterol) to a W/O type upon addition of polyvalent Ca.Inversion of Emulsions (Phase inversion)

Bancroft's ruleEmulsion type depends more on the nature of the emulsifying agent than on the relative proportions of oil or water present or the methodology of preparing emulsion. The phase in which an emulsifier is more soluble constitutes the continuous phase In O/W emulsions emulsifying agents are more soluble in water than in oil (High HLB surfactants). In W/O emulsions emulsifying agents are more soluble in oil than in water (Low HLB surfactants).W/O vs. O/W emulsions

Rate of coalescence measure of emulsion stability. It depends on:Physical nature of the interfacial surfactant film

For Mechanical stability, surfactant films are characterized by strong lateral intermolecular forces and high elasticity Mixed surfactant system preferred over single surfactant. (Lauryl alcohol + Sodium lauryl sulfate: hydrophobic interactions) combination of SPAN and TWEENEmulsions

(b) Electrical or steric barrier

Significant only in O/W emulsions. In case of non-ionic emulsifying agents, charge may arise due to (i) adsorption of ions from the aqueous phase or (ii) contact charging (phase with higher dielectric constant is charged positively)

No correlation between droplet charge and emulsion stability in W/O emulsions

Steric barrier dehydration and change in hydrocarbon chain conformation.Emulsions

(c) Viscosity of the continuous phaseHigher viscosity reduces the diffusion coefficient

Stoke-Einsteins Equation

This results in reduced frequency of collision and therefore lower coalescence. Viscosity may be increased by adding natural or synthetic thickening agents.

Further, as the no. of droplets(many emulsion are more stable in concentrated form than when diluted.)Emulsions

(d) Size distribution of droplets Emulsion with a fairly uniform size distribution is more stable than with the same average droplet size but having a wider size distribution

(e) Phase volume ratioAs volume of dispersed phase stability of emulsion (eventually phase inversion can occur)

(f) TemperatureTemperature , usually emulsion stability Temp affects Interfacial tension, D, solubility of surfactant, Brownian motion, viscosity of liquid, phases of interfacial film.Emulsions

Preparation of emulsionDry gum methodWet gum methodBottle method

Selection of EmulsifiersCorrelation between chemical structure of surfactants andtheir emulsifying power is complicated because(i) Both phases oil and water are of variable compositions.(ii) Surfactant conc. determines emulsifier power as well as the type of emulsion.

Basic requirements:Good surface activityAbility to form a condensed interfacial filmAppropriate diffusion rate (to interface)

Type of emulsion determined by the phase in which emulsifier is placed.

Emulsifying agents that are preferentially oil soluble form W/O emulsions and vice versa.

More polar the oil phase, the more hydrophilic the emulsifier should be. More non-polar the oil phase more lipophilic the emulsifier should be.General Guidelines:

HLB method HLB indicative of emulsification behavior.

HLB3-6 for W/O8-18for O/W

HLB no. of a surfactant depend on which phase of the final emulsion it will become.

Limitation does not take into account the effect of temperature.General Guidelines

2. PIT method At phase inversion temperature, the hydrophilic and lipophilic tendencies are balanced.

Phase inversion temperature of an emulsion is determined using equal amounts of oil and aqueous phase + 3-5% surfactant.

For O/W emulsion, emulsifier should yield PIT of 20-600C higher than the storage temperature.For W/O emulsion, PIT of 10-400C lower than the storage temperature is desired.General Guidelines

Cohesive energy ratio (CER) methodInvolves matching HLBs of oil and emulsifying agents; also molecular volumes, shapes and chemical nature.

Limitation necessary information is available only for a limited no. of compounds.General Guidelines

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