Dr.

jaya raja Kumar Faculty of pharmacy

An emulsion is liquid preparation containing two immiscible liquids, one of which is dispersed as globules (dispersed phase) in the other liquid (continuous phase).
Microemulsion : Droplets size range 0.01 to 0.1m Macroemulsion : Droplets size range approximately 5m

Two Immiscible Liquids

dispersed phase

Dispersed Phase (Internal phase) Continuous Phase (External phase)

continuous phase

An emulsion is a thermodynamically unstable system consisting of at least two immiscible liquid phases one of which is dispersed as globules in the other liquid phase stabilized by a third substance called emulsifying agent.

Emulsions are also called heterogeneous systems or biphasic systems

Examples for emulsions:- milk, rubber latex, crude oil etc.

Phase A Phase B

A.: Two immiscible liquids not emulsified B. An emulsion of phase B dispersed in Phase A C. Unstable emulsion slowly separates. D. The emulsifying agent ( black film) places it self on the interface between phase A and phase B and stabilizes the emulsion.
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Types of emulsions

Simple emulsions (Macro emulsions) Oil-in-water (O/W) Water-in-oil (W/O)

Oil is dispersed phase water is continuous phase

water is dispersed phase oil is continuous phase O/W emulsion W/O emulsion

Multiple emulsions Oil-in-water-in-oil (O/W/O) Water-in-oil-in-water (W/O/W)

Micro emulsions Microemulsions are thermodynamically stable optically transparent , mixtures of a biphasic oil water system stabilized with surfactants.

 Microemulsions are thermodynamically stable optically transparent , mixtures of a biphasic oil water system stabilized with surfactants.

Microemulsion
Transparent Size Formation Type Stability Viscosity Yes 10-120 nm Spontaneous o/w, w/o. cylinder Thermodynamically stable Can accommodate 20 to 40% without increase in viscosity

Emulsion
No 0.1 10 Require vigorous shaking o/w, w/o, w/o/w, o/w/o Thermodynamically unstable More viscous

Increase bioavailability of drugs poorly soluble in water. Topical drug delivery systems

It covers the unpleasant taste Increases absorption rate

i/v lipid nutrients i/m depot effect for water soluble antigenic material

Washable Acceptable viscosity Less greasy

To mask the taste O/W is convenient means of orally administration of waterinsoluble liquids O/W emulsion facilitates the absorption of water-insoluble compounds comparing to their oily solution preparations (e.g. vitamins) Oil-soluble drugs can be given parentrally in form of oil-in water emulsion. (e.g Taxol) Emulsion can be used for external application in cosmetic and therapeutic uses.

using of naked eye, it is very difficult to differentiate between o/w or w/o emulsions. Thus, the four following methods have been used to identify the type if emulsions. Dilution test: In this test the emulsion is diluted either with oil or water. If the emulsion is o/w type and it is diluted with water, it will remain stable as water is the dispersion medium" but if it is diluted with oil, the emulsion will break as oil and water are not miscible with each other.
o/w emulsion can be diluted with water. w/o emulsion can be diluted with oil.

Add drops of water

Add drops of water

Water distribute Uniformly O/W Emulsion W/O Emulsion

Conductivity Test: water is good conductor of electricity whereas oil is non-conductor. Therefore, continuous phase of water runs electricity more than continuous phase of oil.

Emulsion Bulb glows with O/W

Emulsion Bulb doesnt glow with W/O

DYE TEST:

Water Soluble Dye Ex. Amaranth Dye

water is continuous phase Oil is dispersed phase

O/W EMULSION

oil is continuous phase

water is dispersed phase

W/O EMULSION Water-soluble dye will dissolve in the aqueous phase.

Oil Soluble Dye Ex. scarlet

water is continuous phase

Oil is dispersed phase

O/W EMULSION

oil is continuous phase

water is dispersed phase

W/O EMULSION Oil-soluble dye will dissolve in the oil phase.

oils give fluorescence under UV light, while water doesnt. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces. When a w/o emulsion is exposed to fluorescent light under a microscope the entire field fluorescence. If the fluorescence is spotty, then the emulsion is of o/w-type. However, all oils do not exhibit fluorescence under UV light and thus the method does not have universal application. It is necessary that the results obtained by one method should always be confirmed by means of other methods

5.Creaming test. The direction of creaming identifies the emulsion type, if the densities of aqueous and oil phases are known. Water-in-oil emulsions normally cream downward as oil is usually less dense than water. Oil-in-water emulsions normally cream upwards.

6. CoCl2/filter paper test:

Filter paper impregnated with CoCl2 and dried appear to be blue but when dipped in o/w emulsion changes to pink. This test may fail if emulsion unstable or breaks in presence of electrolyte.

 Emulsification is not a spontaneous process and hence emulsions have minimal stability. Reasons for instability can be understood from the nature of immiscible phases and their interfacial properties. When two immiscible liquids are agitated together polar (aqueous) and non polar (oil) liquids are mixed together one of the liquids forms small droplets and gets dispersed in the other liquid forms an emulsion.

 When left aside, droplets fuse themselves and finally separate as two layers.

This in an indication of instability of an emulsion.

Except in the case of very dilute oil-in-water emulsions (oil hydrosols), which are somewhat stable, the liquids separate rapidly into two clearly defined layers.

 The state of instability may be described by the fact that the cohesive force between the molecules of each separate liquid is greater than the adhesive force between the two liquids. Any attempt to increase the adhesive forces between these phases can produce a stable emulsion. A system is said to be thermodynamically stable, if it possesses low surface free energy.

The higher the interfacial area, the greater is the interfacial free energy, and hence lower the stability.

 one of the liquids forms small droplets and gets dispersed in the other liquid
As a result, globules possess an enormously enhanced surface area compared to its original surface area. Consequently, the interfacial energy increases. The relationship is as follows. G = o/w A

(1)

Where G = increase in surface free energy o/w= interfacial tension of oil-water interface A = increase in surface area of the interface due to droplet formation

1. The system spontaneously tries to change back to its original state by decreasing A, so that G will be zero.
The result is the coalescence of globules and separation of phases. The process of coalescence is undesirable for physical stability. thermodynamically unstable Regrouping of globules can be prevented to a great extent by adding a third component called emulsifying agents in emulsions.

2. In equation (1), the interfacial tension, o/w may be reduced, so that the system can be stable. But it cannot be made zero, because the dispersed phases have certain positive interfacial tension. Hence the term G cannot be made zero. However surface active agents are added to reduce o/w value to a minimum. Thus, the system can be stabilized to a certain extent. Certain emulsifying agents can reduce the surface tension thereby prevent coalescence. Such substances are best suited for the preparation of a stable emulsion.

Monomolecular adsorption theory

(a) Reduction in interfacial tension, surface free energy Surface active agents reduce interfacial tension because of their adsorption at the oil-water interface to form monomolecular films.

Surface free energy, W = o/w x A

o/w= interfacial tension of oil-water interface A = increase in surface area of the interface due to droplet formation,

we must retain a high surface area for the dispersed phase. Any reduction in the interfacial tension, o/w , will reduce the surface free energy and hence the tendency for coalescence.

(b) The dispersed droplets are surrounded by a that helps to prevent coalescence between two droplets as they approach one another. Ideally such a so that it is capable of reforming rapidly if broken or disturbed. (c) An additional effect promoting stability is the presence of a surface charge, which will cause between adjacent particles and helps in stabilizing the system. The presence of charges on the surface of oil globules creates an electrical double layer around each globule. Overlapping of these double layer gives rise to repulsion which over single

emulsifier.

 The combination consists of hydrophilic agent in the aqueous phase and a hydrophobic agent in the oil phase forms a . If used individually, sodium cetyl sulphate and cholesterol separate from the emulsion but the combination of the producing an excellent emulsion.

 A combination of sodium cetyl sulphate and oleyl alcohol does not form a and hence a poor emulsion results.

Suitable combinations of a hydrophilic tween and a lipophilic span are widely used to formulated

e.g.: Hydrated lipophilic colloids The emulsifying agents such as acacia and gelatin, tend to form a Their action as emulsifying agents is mainly due to the formation of multimolecular film at the interface and because the films thus formed are strong and resist coalescence. Since the emulsifying agents that form multilayer films around the droplets are , they tend to promote the formation of .

 Finely divided solid particles that are wetted by both oil and water .

They

, where they produce a particulate film around the dispersed droplets and form a around dispersed droplets.

This film acts as a mechanical barrier and prevents the coalescence and tend to produce coarse emulsions. Depending on the affinity of the emulsifier to a particular phase one can prepare both types of emulsions
Powders wetted by water Powders easily wetted by oil o/w emulsions eg., bentonite. w/o emulsions eg., veegum

(a) (b) (c) (d)

Flocculation and creaming Coalescence and breaking Miscellaneous physical and chemical changes Phase inversion.

Flocculation Neighboring globules come closer to each other and form colonies in the continuous phase. This aggregation of globules is not clearly visible. This is the initial stage that leads to instability. Flocculation of the dispersed phase may take place before, during or after creaming.

 The extent of flocculation of globules depends on (a) globule size distribution. (b) charge on the globule surface. (c) viscosity of the external medium. (a) Globule size distribution Uniform sized globules prevent flocculation. This can be achieved by proper size reduction process. (b) Charge on the globule surface A charge on the globules exert repulsive forces with the neighboring globules. This can be achieved by using ionic emulsifying agent, electrolytes etc.

(c) Viscosity of the external medium. If the viscosity of the external medium is increased, the globules become relatively immobile and flocculation can be prevented. This can be obtained by adding viscosity improving agents (bodying agents or thickening agents) such as hydrocolloids or waxes. Flocs slowly move either upward or downward leading to creaming. Flocculation is due to the interaction of attractive and repulsive forces, whereas creaming is due to density differences in the two phases.

Creaming Creaming is the concentration of globules at the top or bottom of the emulsion. Droplets larger than 1 mm may settle preferentially to the top or the bottom under gravitational forces.
Creaming may also be observed on account of the difference of individual globules (movement rather than flocs). It can be observed by a difference in color shade of the layers.

 It is a reversible process, i.e., cream can be redispersed easily by agitation, this is possible because the oil globules are still surrounded by the protective sheath of the emulsifier. Creaming results in a lack of uniformity of drug distribution. This leads to variable dosage. Therefore, the emulsion should be shaken thoroughly before use. Creaming is of two types, upward creaming and downward creaming

 Upward creaming, is due to the dispersed phase is less dense than the continuous phase. This is normally observed in o/w emulsions. The velocity of sedimentation becomes negative.
Downward creaming occurs if the dispersed phase is heavier than the continuous phase. Due to gravitational pull, the globules settle down. This is normally observed in w/o emulsions. Since creaming involves the movement of globules in an emulsion, Stokes law can be applied. = d2 (s 0)g 18 0
= terminal velocity in cm/sec, d is the diameter of the particle in cm, s and 0 are the densities of the dispersed phase and dispersion medium respectively, g is the acceleration due to gravity and 0 is the viscosity of the dispersion medium in poise.

 Creaming is influenced by,

Globule size Viscosity of the dispersion medium Difference in the densities of dispersed phase and dispersion medium.

Creaming can be reduced or prevented by:

1. Reducing the particle size by homogenization. Doubling the diameter of oil globules increases the creaming rate by a factor of four. 2. Increasing the viscosity of the external phase by adding the thickening agents such as methyl cellulose tragacanth or sodium alginate.

3. Reducing the difference in the densities between the dispersed phase and dispersion medium.
Adjusting the continuous phase and dispersed phase densities to the same value should eliminate the tendency to cream. To make densities equal, oil soluble substances such as bromoform, -bromonaphthalene are added to the oil phase (rarely used technique).

Coalescence
If the sizes of globules are not uniform, globules of smaller size occupy the spaces between the larger globules. A few globules tend to fuse with each other and form bigger globules.

This type of closed packing induces greater cohesion which leads to coalescence.

In this process, the emulsifier film around the globules is to a certain extent. This step can be recognized by increased globule size and reduced number of globules.

Coalescence is observed due to: Insufficient amount of the emulsifying agent. Altered partitioning of the emulsifying agent. Incompatibilities between emulsifying agents. Phase volume ratio of an emulsion has a secondary influence on the stability of the product and represents the relative volume of water to oil in emulsion.

 At higher ratio (>74% of oil to water), globules are closely packed, wherein small globules occupy the void spaces between bigger globules.
Thus globules get compressed and become irregular in shape, which leads to fusion of adjacent globules. Ostwald and others have shown that if one attempts to incorporate more than about 74% of oil in an o/w emulsion, the oil globules often coalesce and the emulsion breaks. This value known as the critical point, is defined as the concentration of the dispersed phase above which the emulsifying agent cannot produce a stable emulsion of the desired type.

Breaking
Separation of the internal phase from the external phase is called breaking of the emulsion. This is indicated by complete separation of oil and aqueous phases, is an irreversible process, i.e., simple mixing fails. It is to resuspend the globules into an uniform emulsion. In breaking, the protective sheath around the globules is completely destroyed and oil tends to coalesce.

Phase inversion This involves the change of emulsion type from o/w to w/o or vice versa. When we intend to prepare one type of emulsion say o/w, and if the final emulsion turns out to be w/o, it can be termed as a sign of instability.