DEFINITION
An emulsion is a thermodynamically unstable dispersed system consisting of at least two immiscible liquid phase, one of which is dispersed as globules in the other liquid phase.
The system is stabilized by the presence of an emulsifying agent.
Emulsified systems range from lotions of relatively low viscosity to ointments and creams, which are semisolid in nature.
The particle diameter of the dispersed phase generally extends from about 0.1 to 10 mm and as 100 mm are not uncommon in some preparations.
TYPES OF EMULSIONS
(I) Ordinary emulsion systems / Primary emulsion systems / Simple emulsion systems
(i) o/w type - oil dispersed in water
oil ® dispersed phase
water ® continuous phase
(ii) w/o type - water dispersed in oil
water ® dispersed phase
oil ® continuous phase
(II) Special emulsion systems
(i) Multiple emulsions ® w/o/w - type
o/w/o - type
(ii) Micro emulsion
Simple emulsion type:
o/w- type of emulsion is a system in which the oil is dispersed as droplet throughout the aqueous phase. Most pharmaceutical emulsions designed for oral administration are of the o/w type; emulsified lotions and creams either of o/w or w/o type depending on their use.
Certain foods such as butter and some salad creams are w/o type emulsions.
Multiple emulsion type
These multiple emulsions have been developed with a view to delay the release of an active ingredient. In this type of emulsions three phases are present, i.e. the emulsion has the form w/o/w or o/w/o. In these “emulsions within emulsions”, any drug present in the innermost phase now has to cross two phase-boundaries to reach the external continuous phase.
I : Continuous phase (External aqueous phase)
II: Middle oil phase
III: Inner aqueous phaseAdvantages of multiple emulsions
(i) Prolongation of drug action
(ii) Location of drug in the body.
Micro emulsions
Microemulsions are liquid dispersion of water and oil that are made homogeneous, transparent and stable by the addition of relatively large amount of a surfactant and a co-surfactant. They appear to represent a state intermediate between thermodynamically unstable emulsions and solubolised systems.
Unlike emulsions, they appear as clear transparent solution, but unlike solubilised systems micro-emulsions may not be thermodynamically stable.
Microemulsions containing droplets (w/o or o/w types) with the globule size 10 to 200nm and the volume fraction of the dispersed phase varies from 0.2 to 0.8.
DETERMINATION OF EMULSION TYPE
Several methods are commonly used to determine the type of emulsion. The types of emulsion determined by one method should always be confirmed by means of second method.
(1) Dye solubility test
A small amount of a water soluble dye (e.g. methylene blue or brilliant blue) may be dusted on the surface of the emulsion.
If water is the external phase (i.e. o/w type) then the dye will be dissolved uniformly throughout the media.
If the emulsion is of the w/o -type then particles of dye will lie in clumps on the surface.
(2) Dilution test
This method involves dilution of the emulsion with water. If the emulsion mixes freely with the water, it is of o/w -type. Generally, addition of disperse phase will crack an emulsion.
(3) Conductivity test
This test employs a pair of electrodes connected to an external electric source and immersed in the emulsion. If the external phase is water, a current will pass through the emulsion and can be made to deflect a volt-meter needle or cause a light in the circuit to glow. if the oil is the continuous phase then the emulsion will fail to carry the current.
4. Fluorescence test
If an emulsion on exposure to ultra-violet radiations shows continuous fluorescence under microscope, then it is w/o type and if it shows only spotty fluorescence, then it is o/w type.
5.Cobalt Chloride Test:
When a filter paper soaked in cobalt chloride solution is dipped in to an emulsion and dried, it turns from blue to pink, indicating that the emulsion is o/w type.
-May fail if ionic emulsifiers are present.
-Fails in nonionic o/w emulsions.
-Not always applicable
-May fail if emulsion is unstable or breaks in presence of electrolyte.
FORMULATION OF EMULSION
In developing the formula of an emulsion the crucial decisions are related to the choice of the aqueous and oil phases and of the emulgents and their relative proportions. There can be no general guideline in this respect and the choice of phases and emulgents should be related to the qualities desired for the final product. Usually, ingredient selection is made on the basis of the experience and personal tastes of the formulator and by trial and error.
CHEMICAL PARAMETERS
Chemical stability
All the ingredients of an emulsion should be chemically compatible.
e.g. a soap cannot be used as an emulsifier in a system having a final pH of less than 5.
e.g. some lipids are subjected to chemical changes due to oxidation (rancidity); so in general it is simpler to avoid their use than to depend on antioxidants
Safety
All the ingredients should pass the toxicological tests. It is essential, therefore, for the formulator to depend heavily on toxicologic information from suppliers or in the scientific literature, and on regulatory activities by governmental agencies.
Choice of lipid phase
The choice of lipid phase depends on the ultimate use of the product.
(i) If the oily phase is the active-ingredient itself (e.g. liquid paraffin emulsion) the formulator has nothing to chose from.
(ii) The drug in a pharmaceutical preparation should not be too soluble in lipid phase then it will reduce the rate of transfer of the drug molecule to other phases.
(iii) Emulsions prepared for topical purpose (e.g. cosmetics and pharmaceutical emulsions) should possess a good “feel”. Emulsions normally leave a residue of the oily components on the skin after the water has evaporated. Therefore, the tactile characteristics of the combined oil phase are of great importance in determining consumer acceptance of an emulsion
Phase - volume ratio
The ratio of the internal phase to the external phase is frequently determined by the solubility of the active ingredients, which must provide the required dose.
If this is not the primary criteria, the phase ratio is normally determined by the desired consistency of the product. For liquid emulsions the limits of internal phase vary from 40 to 60%, since with such amounts a stable and acceptable emulsion can be prepared. Lower amounts of internal phase (i.e. disperse phase) gives a product of low viscosity with pronounced degree of creaming while higher percentage may produce highly viscous emulsions with tendency of phase inversion.
TABLE 1: Ingredients for oil-phase of emulsions
Class
Identity
Consistency
Hydrocarbon
Hydrocarbon
Hydrocarbon
Hydrocarbon
Ester
Ester
Ester
Ester
Alcohols
Fatty acids
Ethers
Silicones
Mixed
Mixed
Mineral oils
Petrolatum
Polyethylene waxes
Microcrystalline waxes
Vegetable oils
Animal fats
Lanolin
Synthetic (e.g. isopropyl myristate)
Long chain (natural & synthetic)
Long chain (natural & synthetic)
Polyoxypropylenes
Substituted silicones
Plant waxes (e.g. Candellia)
Animal waxes (e.g. Beeswax)
Fluids of varying viscosity
Semisolid
Solids
Solids
Fluids of varying viscosity
Fluids or solids
Semisolid
Fluids
Fluids or solids
Fluids or solids
Fluids of varying viscosity
Fluids of varying viscosity
Solid
Solid
Choice of emulsifying agents / Emulsifiers / Emulgents
Emulsifying agents are broadly classified into three classes:
(i) Synthetic emulsifying agent / Surface active agents (SAA) / Surfactants
(ii) Hydrophilic colloid
(iii) Finely divided solids
When an emulsifier is used alone to stabilize an emulsion - it is called primary emulsifier. Some times a second emulsifier is used to help the primary emulsifier in stabilizing the system - the second emulsifier is known as auxiliary emulsifier. Generally emulsifiers from (ii) and (iii) category are used both as primary and auxiliary emulsifier.
A successful emulsifier must possess some or all of the following characteristics:
(a) The surface tension should be reduced to a value less than 10 dynes/cm2.
(b) A complete and coherent film should be formed around the dispersed globules so as to prevent their coalescence.
(c) Should assist in building up the zeta potential and viscosity since both of these phenomena contribute to the stability.
Choice of synthetic surface active agents / Surfactants:
Molecules and ions that are absorbed at interfaces are termed surface-active-agents or surfactants. An alternative expression is amphiphile, which suggests that the molecule or ion has a certain affinity for both polar and nonpolar solvents. Due to the amphiphilic nature of surfactants they absorb at the oil-water interface.
Griffin devised an arbitrary scale of values to serve as a measure of the hydrophilic-lipophilic balance (HLB) of surface-active -agents.
An emulsion is a thermodynamically unstable dispersed system consisting of at least two immiscible liquid phase, one of which is dispersed as globules in the other liquid phase.
The system is stabilized by the presence of an emulsifying agent.
Emulsified systems range from lotions of relatively low viscosity to ointments and creams, which are semisolid in nature.
The particle diameter of the dispersed phase generally extends from about 0.1 to 10 mm and as 100 mm are not uncommon in some preparations.
TYPES OF EMULSIONS
(I) Ordinary emulsion systems / Primary emulsion systems / Simple emulsion systems
(i) o/w type - oil dispersed in water
oil ® dispersed phase
water ® continuous phase
(ii) w/o type - water dispersed in oil
water ® dispersed phase
oil ® continuous phase
(II) Special emulsion systems
(i) Multiple emulsions ® w/o/w - type
o/w/o - type
(ii) Micro emulsion
Simple emulsion type:
o/w- type of emulsion is a system in which the oil is dispersed as droplet throughout the aqueous phase. Most pharmaceutical emulsions designed for oral administration are of the o/w type; emulsified lotions and creams either of o/w or w/o type depending on their use.
Certain foods such as butter and some salad creams are w/o type emulsions.
Multiple emulsion type
These multiple emulsions have been developed with a view to delay the release of an active ingredient. In this type of emulsions three phases are present, i.e. the emulsion has the form w/o/w or o/w/o. In these “emulsions within emulsions”, any drug present in the innermost phase now has to cross two phase-boundaries to reach the external continuous phase.
I : Continuous phase (External aqueous phase)
II: Middle oil phase
III: Inner aqueous phaseAdvantages of multiple emulsions
(i) Prolongation of drug action
(ii) Location of drug in the body.
Micro emulsions
Microemulsions are liquid dispersion of water and oil that are made homogeneous, transparent and stable by the addition of relatively large amount of a surfactant and a co-surfactant. They appear to represent a state intermediate between thermodynamically unstable emulsions and solubolised systems.
Unlike emulsions, they appear as clear transparent solution, but unlike solubilised systems micro-emulsions may not be thermodynamically stable.
Microemulsions containing droplets (w/o or o/w types) with the globule size 10 to 200nm and the volume fraction of the dispersed phase varies from 0.2 to 0.8.
DETERMINATION OF EMULSION TYPE
Several methods are commonly used to determine the type of emulsion. The types of emulsion determined by one method should always be confirmed by means of second method.
(1) Dye solubility test
A small amount of a water soluble dye (e.g. methylene blue or brilliant blue) may be dusted on the surface of the emulsion.
If water is the external phase (i.e. o/w type) then the dye will be dissolved uniformly throughout the media.
If the emulsion is of the w/o -type then particles of dye will lie in clumps on the surface.
(2) Dilution test
This method involves dilution of the emulsion with water. If the emulsion mixes freely with the water, it is of o/w -type. Generally, addition of disperse phase will crack an emulsion.
(3) Conductivity test
This test employs a pair of electrodes connected to an external electric source and immersed in the emulsion. If the external phase is water, a current will pass through the emulsion and can be made to deflect a volt-meter needle or cause a light in the circuit to glow. if the oil is the continuous phase then the emulsion will fail to carry the current.
4. Fluorescence test
If an emulsion on exposure to ultra-violet radiations shows continuous fluorescence under microscope, then it is w/o type and if it shows only spotty fluorescence, then it is o/w type.
5.Cobalt Chloride Test:
When a filter paper soaked in cobalt chloride solution is dipped in to an emulsion and dried, it turns from blue to pink, indicating that the emulsion is o/w type.
-May fail if ionic emulsifiers are present.
-Fails in nonionic o/w emulsions.
-Not always applicable
-May fail if emulsion is unstable or breaks in presence of electrolyte.
FORMULATION OF EMULSION
In developing the formula of an emulsion the crucial decisions are related to the choice of the aqueous and oil phases and of the emulgents and their relative proportions. There can be no general guideline in this respect and the choice of phases and emulgents should be related to the qualities desired for the final product. Usually, ingredient selection is made on the basis of the experience and personal tastes of the formulator and by trial and error.
CHEMICAL PARAMETERS
Chemical stability
All the ingredients of an emulsion should be chemically compatible.
e.g. a soap cannot be used as an emulsifier in a system having a final pH of less than 5.
e.g. some lipids are subjected to chemical changes due to oxidation (rancidity); so in general it is simpler to avoid their use than to depend on antioxidants
Safety
All the ingredients should pass the toxicological tests. It is essential, therefore, for the formulator to depend heavily on toxicologic information from suppliers or in the scientific literature, and on regulatory activities by governmental agencies.
Choice of lipid phase
The choice of lipid phase depends on the ultimate use of the product.
(i) If the oily phase is the active-ingredient itself (e.g. liquid paraffin emulsion) the formulator has nothing to chose from.
(ii) The drug in a pharmaceutical preparation should not be too soluble in lipid phase then it will reduce the rate of transfer of the drug molecule to other phases.
(iii) Emulsions prepared for topical purpose (e.g. cosmetics and pharmaceutical emulsions) should possess a good “feel”. Emulsions normally leave a residue of the oily components on the skin after the water has evaporated. Therefore, the tactile characteristics of the combined oil phase are of great importance in determining consumer acceptance of an emulsion
Phase - volume ratio
The ratio of the internal phase to the external phase is frequently determined by the solubility of the active ingredients, which must provide the required dose.
If this is not the primary criteria, the phase ratio is normally determined by the desired consistency of the product. For liquid emulsions the limits of internal phase vary from 40 to 60%, since with such amounts a stable and acceptable emulsion can be prepared. Lower amounts of internal phase (i.e. disperse phase) gives a product of low viscosity with pronounced degree of creaming while higher percentage may produce highly viscous emulsions with tendency of phase inversion.
TABLE 1: Ingredients for oil-phase of emulsions
Class
Identity
Consistency
Hydrocarbon
Hydrocarbon
Hydrocarbon
Hydrocarbon
Ester
Ester
Ester
Ester
Alcohols
Fatty acids
Ethers
Silicones
Mixed
Mixed
Mineral oils
Petrolatum
Polyethylene waxes
Microcrystalline waxes
Vegetable oils
Animal fats
Lanolin
Synthetic (e.g. isopropyl myristate)
Long chain (natural & synthetic)
Long chain (natural & synthetic)
Polyoxypropylenes
Substituted silicones
Plant waxes (e.g. Candellia)
Animal waxes (e.g. Beeswax)
Fluids of varying viscosity
Semisolid
Solids
Solids
Fluids of varying viscosity
Fluids or solids
Semisolid
Fluids
Fluids or solids
Fluids or solids
Fluids of varying viscosity
Fluids of varying viscosity
Solid
Solid
Choice of emulsifying agents / Emulsifiers / Emulgents
Emulsifying agents are broadly classified into three classes:
(i) Synthetic emulsifying agent / Surface active agents (SAA) / Surfactants
(ii) Hydrophilic colloid
(iii) Finely divided solids
When an emulsifier is used alone to stabilize an emulsion - it is called primary emulsifier. Some times a second emulsifier is used to help the primary emulsifier in stabilizing the system - the second emulsifier is known as auxiliary emulsifier. Generally emulsifiers from (ii) and (iii) category are used both as primary and auxiliary emulsifier.
A successful emulsifier must possess some or all of the following characteristics:
(a) The surface tension should be reduced to a value less than 10 dynes/cm2.
(b) A complete and coherent film should be formed around the dispersed globules so as to prevent their coalescence.
(c) Should assist in building up the zeta potential and viscosity since both of these phenomena contribute to the stability.
Choice of synthetic surface active agents / Surfactants:
Molecules and ions that are absorbed at interfaces are termed surface-active-agents or surfactants. An alternative expression is amphiphile, which suggests that the molecule or ion has a certain affinity for both polar and nonpolar solvents. Due to the amphiphilic nature of surfactants they absorb at the oil-water interface.
Griffin devised an arbitrary scale of values to serve as a measure of the hydrophilic-lipophilic balance (HLB) of surface-active -agents.
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