EMULSIONS

EMULSIONSEMULSIONSEMULSIONSEMULSIONS

An emulsion is a dispersion in which the An emulsion is a dispersion in which the dispersed phase is composed of small dispersed phase is composed of small globules of a liquid distributed globules of a liquid distributed throughout a vehicle in which it is throughout a vehicle in which it is immiscible.immiscible.

IntroductionIntroduction

EMULSIONSEMULSIONSEMULSIONSEMULSIONS

Based on dispersed phase• Oil in Water (O/W): Oil droplets dispersed in water• Water in Oil (W/O): Water droplets dispersed in oil• Multiple Emulsion (W-O-W): Water droplet enclosed in an oil droplet which is itself dispersed in water

Classification of Classification of emulsions :emulsions :

Classification of Classification of emulsions :emulsions :

Based on size of liquid droplets

0.2 – 50 mm Macroemulsions (Kinetically Stable) 0.01 – 0.2 mm Microemulsions (Thermodynamically Stable)

Emulsions encountered in everyday life! Emulsions encountered in everyday life!

Metal cutting oils Margarine Ice cream

Pesticide Asphalt Skin cream

Stability of emulsions may be Stability of emulsions may be engineered to vary from seconds to engineered to vary from seconds to

years depending on application years depending on application

General Types of Pharmaceutical General Types of Pharmaceutical Emulsions:Emulsions:

1) Lotions 1) Lotions 2) Liniments2) Liniments 3) Creams3) Creams 4) Ointments4) Ointments 5) Vitamin drops5) Vitamin drops

Theories of Theories of EmulsificationEmulsification::

1) Surface Tension Theory:1) Surface Tension Theory:

- lowering of interfacial tension.- lowering of interfacial tension.

2) Oriented-Wedge Theory:2) Oriented-Wedge Theory:

- mono molecular layers of - mono molecular layers of emulsifying emulsifying agents are curved agents are curved around a droplet of the around a droplet of the internal internal phase of the emulsion.phase of the emulsion.

Theories of Theories of EmulsificationEmulsification::

3) Interfacial film theory:3) Interfacial film theory:

- A film of emulsifying - A film of emulsifying agent prevents agent prevents the contact the contact and coand coaalescing of the lescing of the dispersed phase.dispersed phase.

Emulsifying Agents:Emulsifying Agents:

It is a substance which It is a substance which stabilizes an stabilizes an emulsion .emulsion . It helps the production of stable It helps the production of stable emulsion emulsion by:by:

1.) reducing interfacial 1.) reducing interfacial tension tension

2.) maintaining the 2.) maintaining the separation by separation by

forming a barrier at the forming a barrier at the interface.interface.

be stable . be compatible with other ingredients . be non – toxic . non-irritant. possess little odor , taste , or color . able to produce stable emulsions at low concentrations. not interfere with the stability of efficacy of the active agent .

Pharmaceutically acceptable emulsifiers must also :

Emulsifying AgentsEmulsifying Agents::

1) Carbohydrate Materials:1) Carbohydrate Materials: (o/w (o/w emulsion)emulsion)

Naturally occuring:Naturally occuring:

- Acacia- Acacia (best emulsifying agent) (best emulsifying agent)

- - TragacanthTragacanth (increase the viscosity of (increase the viscosity of emulsion)emulsion)

- - AgarAgar

- - Pectin. Pectin.


2) Protein Substances:2) Protein Substances: (o/w emulsion) (o/w emulsion)

Naturally occuring:Naturally occuring:

-- GelatinGelatin

- - Egg yolkEgg yolk

- - Caesin Caesin


3) High Molecular Weight Alcohols:3) High Molecular Weight Alcohols:

- Stearyl Alcohol- Stearyl Alcohol

- - Cetyl AlcoholCetyl Alcohol o/w o/w emulsion,emulsion,

- - Glyceryl Mono stearate Glyceryl Mono stearate

- - cholesterol cholesterol ((w/o emulsionw/o emulsion))


4) Finely divided solids:4) Finely divided solids:

- it form a coherent film that prevents - it form a coherent film that prevents

coalescence of the dispersed globules.coalescence of the dispersed globules.

e.g.e.g.

Bentonite, Magnesium Hydroxide, Bentonite, Magnesium Hydroxide,

Aluminum Hydroxide o/w emulsion.Aluminum Hydroxide o/w emulsion.


4) Finely divided solids:4) Finely divided solids:

solid (wetted) oil solid (wetted) oil -- W/O W/O emulsion emulsion

solid (wetted) watersolid (wetted) water -- O/W O/W emulsionemulsion

(good stability which are less prone to (good stability which are less prone to microbial contaminations.)microbial contaminations.)


5) Wetting Agents:5) Wetting Agents:

Anionic, Cationic, NonionicAnionic, Cationic, Nonionic

o/w emulsiono/w emulsion

w/o emulsionw/o emulsion

SYNTHETIC SURFACTANTSSYNTHETIC SURFACTANTS

ANIONIC - organic salts which in water ANIONIC - organic salts which in water have a have a

surface active anion.surface active anion.• alkali metal & ammonium soaps such as alkali metal & ammonium soaps such as

sodium stearatesodium stearate• soaps of divalent & trivalent metalssoaps of divalent & trivalent metals• amine soaps such as amine soaps such as triethanolamine triethanolamine

oleateoleate (O/W) (O/W)• alkyl sulfates - alkyl sulfates - sodium lanoxyl sulfatesodium lanoxyl sulfate

SYNTHETIC SURFACTANTSSYNTHETIC SURFACTANTS

CATIONIC - quarternary ammonium CATIONIC - quarternary ammonium compounds which have a surface active compounds which have a surface active cation and so are sensitive to anionic cation and so are sensitive to anionic surfactants and drugs.surfactants and drugs.

NON-ANIONIC - makes the largest NON-ANIONIC - makes the largest group of surfactants.group of surfactants.

e.g.e.g. Lecithin, Polysorbate 80, Lecithin, Polysorbate 80, Methylcellulose, Methylcellulose, Gelatin, Serum Gelatin, Serum albuminalbumin

SOME PRESERVATIVES USED IN SOME PRESERVATIVES USED IN EMULSIONEMULSION

1.1. Benzoic acid - effective at concentration Benzoic acid - effective at concentration 0.1% 0.1%

2.2. PHBZ - methyl paraben (0.01 - 0.3% v/v)PHBZ - methyl paraben (0.01 - 0.3% v/v)3.3. Chloroform as water (0.25%)Chloroform as water (0.25%)4.4. Chlorocresol (0.5 - 0.2%)Chlorocresol (0.5 - 0.2%)5.5. Phenoxyethanol (0.5 - 1.0%)Phenoxyethanol (0.5 - 1.0%)6.6. Benzyl Alcohol (0.1 - 3%)Benzyl Alcohol (0.1 - 3%)7.7. Quarternary Ammonium compounds Quarternary Ammonium compounds

(cetrimide)(cetrimide)8.8. Organic Mercurial compounds (phenyl Organic Mercurial compounds (phenyl

mercuric nitrate & acetate)mercuric nitrate & acetate)

Methods of Preparation of Methods of Preparation of Emulsions:Emulsions:

1) Continental or Dry Gum Method:1) Continental or Dry Gum Method:

"4:2:1" Method"4:2:1" Method

4 parts (volumes) of oil4 parts (volumes) of oil

2 parts of water2 parts of water

1 part of gum1 part of gum

2) English or wet Gum Method:2) English or wet Gum Method:

4 parts (volumes) of oil4 parts (volumes) of oil

2 parts of water2 parts of water

1 part of gum1 part of gum

3) Bottle or Forbes Bottle Method:3) Bottle or Forbes Bottle Method: useful for extemporaneous preparation useful for extemporaneous preparation

of emulsion from volatile oils or of emulsion from volatile oils or oleaginous substance of low viscosity.oleaginous substance of low viscosity.

powdered acaciapowdered acacia

+ Dry bottle+ Dry bottle

2 parts of oil2 parts of oil

This method is not suitable for viscous This method is not suitable for viscous oils (i.e. high viscosity oil).oils (i.e. high viscosity oil).

Means of DetectionMeans of Detection of Type of of Type of EmulsionEmulsion

Tests for Emulsion Type Tests for Emulsion Type

11) ) Dilution TestDilution Test::

- - oo//w emulsion can be diluted with w emulsion can be diluted with waterwater..

- - ww//o emulsion can be diluted with o emulsion can be diluted with oiloil..

Means of DetectionMeans of Detection of Type of of Type of EmulsionEmulsion


2) Conductivity Test:2) Conductivity Test:- - Continuous phase water > Continuous phase water > Continuous Continuous phase oil.phase oil.e.g.e.g.

system with aqueous continuous system with aqueous continuous phase will phase will conduct electricityconduct electricity

Emulsion Type and Means of Emulsion Type and Means of DetectionDetection


3) Dye-Solubility Test:3) Dye-Solubility Test: - water soluble dye will dissolve in the - water soluble dye will dissolve in the

aqueous phaseaqueous phase, while , while oil soluble dye will oil soluble dye will dissolve in the oil phase.dissolve in the oil phase.e.g.e.g.

O/WO/W -- colored globulescolored globulesW/OW/O -- colorless globulescolorless globules

Emulsion Type and Means of Emulsion Type and Means of DetectionDetection


4) Refractive index measurement4) Refractive index measurement- For the emulsion to be transparent the - For the emulsion to be transparent the refractive index of the two phases refractive index of the two phases should match.should match.

5) Filter paper test5) Filter paper test- Filter paper impregnated with Cobalt - Filter paper impregnated with Cobalt Chloride Chloride

blue blue -- pinkpink

Rate of coalescenceRate of coalescence The The measure of emulsion stability.measure of emulsion stability. It depends on:It depends on:

1. Physical nature of the interfacial 1. Physical nature of the interfacial surfactant film surfactant film

For Mechanical stability, surfactant For Mechanical stability, surfactant films are characterized by strong lateral films are characterized by strong lateral intermolecular forces and high elasticity intermolecular forces and high elasticity

(Analogous to stable foam bubbles)(Analogous to stable foam bubbles)

Rate of coalescenceRate of coalescence

2. Electrical or steric barrier2. Electrical or steric barrier Significant only in O/W emulsions.Significant only in O/W emulsions.

In case of non-ionic emulsifying agents, charge In case of non-ionic emulsifying agents, charge may arise due to:may arise due to:

• (i) adsorption of ions from the aqueous (i) adsorption of ions from the aqueous phase orphase or

• (ii) contact charging (phase with higher (ii) contact charging (phase with higher dielectric constant is charged positively)dielectric constant is charged positively)

Steric barrier – dehydration and change in Steric barrier – dehydration and change in hydrocarbon chain conformation.hydrocarbon chain conformation.


3. Viscosity of the continuous phase3. Viscosity of the continuous phase many emulsion are more stable in many emulsion are more stable in

concentrated form than when diluted.concentrated form than when diluted. Viscosity may be increased by adding Viscosity may be increased by adding

natural or synthetic thickening agents.natural or synthetic thickening agents.


4. Size distribution of droplets4. Size distribution of droplets

Emulsion with a fairly uniform size Emulsion with a fairly uniform size distribution is more stabledistribution is more stable

5. Phase volume ratio5. Phase volume ratio

As volume of dispersed phase increases As volume of dispersed phase increases stability of emulsion decreasesstability of emulsion decreases

(eventually phase inversion can occur)(eventually phase inversion can occur)


6. Temperature6. Temperature

As the temperature increases, usually As the temperature increases, usually emulsion stability decreases.emulsion stability decreases.

Temp affects – Interfacial tension, D, Temp affects – Interfacial tension, D, solubility of surfactant, viscosity of liquid, solubility of surfactant, viscosity of liquid, phases of interfacial film.phases of interfacial film.

PHASE INVERSIONPHASE INVERSION

- process in which an emulsion - process in which an emulsion changes from one type to another.changes from one type to another.

e.g.e.g.• If a substance is added which If a substance is added which

alters the alters the solubility of the solubility of the emulsifying agent, the emulsifying agent, the balance balance may be altered and the emulsion may may be altered and the emulsion may

change type.change type.

Inversion of Emulsions (Phase Inversion of Emulsions (Phase inversion)inversion)

O/WO/W W/O W/O

1.1. The order of addition of the phasesThe order of addition of the phasesW W O + emulsifier O + emulsifier W/O W/OO O W + emulsifier W + emulsifier O/W O/W

2.2. Nature of emulsifierNature of emulsifierMaking the emulsifier more oil soluble Making the emulsifier more oil soluble tends to produce a W/O emulsion and vice tends to produce a W/O emulsion and vice versa.versa.


3.3. Phase volume ratioPhase volume ratioOil/Water ratioOil/Water ratio W/O emulsion and vice W/O emulsion and vice versaversa

4.4. Temperature of the system Temperature of the systemTemperature of O/W makes the emulsifier Temperature of O/W makes the emulsifier more hydrophobic and the emulsion may more hydrophobic and the emulsion may invert to W/O.invert to W/O.


5.5. Addition of electrolytes and other additives. Addition of electrolytes and other additives.Strong electrolytes to O/W (stabilized by Strong electrolytes to O/W (stabilized by ionic surfactants) may invert to W/Oionic surfactants) may invert to W/O

Example. Inversion of O/W emulsion Example. Inversion of O/W emulsion (stabilized by sodium cetyl sulfate and (stabilized by sodium cetyl sulfate and cholesterol) to a W/O type upon addition of cholesterol) to a W/O type upon addition of polyvalent Ca.polyvalent Ca.

SOURCES OF CONTAMINATIONSOURCES OF CONTAMINATION

1.1. Natural emulsifying agents (starch & Natural emulsifying agents (starch & acacia)acacia)

2.2. WaterWater

3.3. Carelessly cleaned equipmentsCarelessly cleaned equipments

4.4. Poor closure on containersPoor closure on containers

STABILITY OF EMULSIONSTABILITY OF EMULSION

CREAMING -aggregation of globules CREAMING -aggregation of globules of the of the disperse phase at disperse phase at the top or the top or bottom of bottom of the emulsion.the emulsion.

CRACKING -coalescence of CRACKING -coalescence of dispersed dispersed globules globules and separation of the and separation of the disperse phase as a separate layer.disperse phase as a separate layer.

CAUSES OF CRACKING & CAUSES OF CRACKING & CREAMINGCREAMING

1.1. Globule sizeGlobule size

2.2. Storage temperatureStorage temperature

3.3. Potential for globule coalescencePotential for globule coalescence

4.4. Changes which affect the interfacial Changes which affect the interfacial filmfilm

Separation of the internal phase from Separation of the internal phase from the external phase is called the external phase is called BREAKINGBREAKING of the emulsion. This is irreversible.of the emulsion. This is irreversible.

Protect emulsions against the extremes Protect emulsions against the extremes of cold and heat.of cold and heat.

Emulsions may be adversely affected by Emulsions may be adversely affected by microbial contamination.microbial contamination.

Emulsion Emulsion BreakingBreaking

SPECIAL LABELINGSPECIAL LABELING

Shake well before useShake well before use Store in cool placeStore in cool place Expiry dateExpiry date For external use onlyFor external use only

General Guidelines:General Guidelines:

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

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

General Guidelines:General Guidelines:

3.3. The mThe more polar the oil phase, the more ore polar the oil phase, the more hydrophilic the emulsifier should be. More hydrophilic the emulsifier should be. More non-polar the oil phase more lipophilic the non-polar the oil phase more lipophilic the emulsifier should be.emulsifier should be.

EMULSIONS

Health & Medicine

stable emulsions

dispersed phasean emulsion

viscosity of emulsion

dispersed phase oil

water water

film of emulsifying

tostability of emulsions

interfacial film theory