PHYSICAL PHARMACEUTICS

“EMULSIONS”

Topics Emulsifying agents m/a of emulsifying agents Physical instability – Markers Factors improving Physical Stability Phase inversion Evaluation of physical stability Preparation of Emulsions

EMULSIONSEmulsions are biphasic systems in which both

phases are liquids.

EMULSIFYING AGENTS

Emulsifying agents stabilize emulsions by preventing or reducing the coalescence of

dispersed globules.

A variety of emulsifying agents are used, each probably act by different mechanisms. Irrespective of their chemical nature, they tend to concentrate at the interface and form a tough film around the globules.

CLASSIFICATION

Based on the types of films:-•Surface active agents (soaps, span, tween).•Hydrophilic colloids (acacia, gelatin).•Finely divided solids (bentonite, veegum).

Based on nature of films:-•Monomolecular adsorption & film formation.•Multimolecular adsorption.•Solid particle adsorption.

Mono molecular adsorption and film formationSurfactants adsorb at oil water interface and form a mono molecular film. This film rapidly envelops the droplets as soon as they are formed. Agents having higher interfacial activity are better suited for this purpose. The mono molecular film should be compact and strong enough so that if film is broken, it should be elastic and flexible enough, so that it can be reformed rapidly on moderate agitation.

Surfactants are capable of “REDUCING THE INTERFACIAL TENSION”. This facilitates the immediate formation of small droplets. Its importance can be understood by considering the surface free energy changes during emulsification. Formation of smaller droplets is important in preparation in emulation

ΔG=0Surfactants achieve this objective and produce stable emulsion.

Ionic surfactants impart charges on interfacial films. This films exerts repulsive force between two approaching globule and prevent their coalescence.

Combination of 2 surfactants give better effect.

Here Tween 40 and Span 80 and mixed together for better effect.

Multimolecular Adsorption

These emulsifying agents such as acacia and gelatin, (isoelectric point) tend from Multimolecular film around the globules and prevent coalescence. They also reduce interfacial tension moderately, through it is secondary importance. They are effective at high concentration and promote the formation o/w emulsion owing to their hydrophilicity. They also have affinity toward the oil phase and facilitate interfacial adsorption. Normally, this stability is improved by adding viscosity inducing agents such as tragacanths methy1 cellulose CMC etc….

Solid particle adsorption

The finely divided solid particles adsorbs at oil-water interface and form a rigid film of closely packed solids. This film acts as a mechanical barrier and prevents the coalescence of globules. These tend to produce coarse emulsion. Depending on the affinity of emulsifier to particular phase, one can prepare both types of emulsions.

Examples are:

Bentonite (hydrated aluminum silicate, PH-9) ----- o/w & w/oVeegum (magnesium aluminum silicate, >1%) ---- o/w

The stability of an emulsion depends on finer state of subdivision of solid particles, irregular surface and charge on surface.

Flocculation Creaming Coalescence Breaking Phase inversion

1. Coalescence 2. Flocculation

3. Creaming 4. Breaking

GOODEMULSION

Flocculation In this case neighboring globules come closer to each other and form colonies in external phase. This aggregation of globules is not clearly visible. The flocculation of globules depend on:

•Globule size distribution.•Charge on globule surface.•Viscosity of external medium.

Uniform sized globules prevent flocculation. This can be achieved by proper size reduction process. If the viscosity of external medium is increased, the globules become relatively immobile and flocculation can be prevented. Flocs slowly move either upward or downward leading to creaming. Flocculation is due to interaction of attractive and repulsive force, where as creaming is due to density differences in two phases …

Creaming

Creaming can be prevented by:

1. Reducing the particle size by homogenization.

2. Increasing the viscosity of external phase by adding the thickening agents.

3. Reducing the difference in densities between dispersed phase and dispersion medium.

COALESCENCEA few globules tend to fuse with each other and form bigger globules.

Coalescence is observed due to:--Insufficient amount of emulsifying agent-Altered partitioning of emulsifying agent

-Incompatibilities between emulsifying agents

BreakingThis is indicated by complete separation of oil and aqueous phase. It is an irreversible process i.e. simple mixing fails to re suspend the globules into a uniform emulsion. In breaking, protective sheath around the globules is completely destroyed.

FACTORS

IMPROVING

Particle size:- Globule size is REDUCED to exhibit Brownian motion to maintain stability of emulsions. Particle size distribution:- Range must

be less varied to maintain good stability.

Viscosity:- As it increases, the flocculation is hindered and creaming occurs, therefore optimum Viscosity is necessary. Phase Volume Ratio:- It represents

the relative volume of water to oil in an emulsion.Charge of electric Double layer:- This

factor is only applied when there is use of Ionic surfactant. Physical properties of Interface:- The

film should be elastic enough to form rapidly as soon as droplets are formed.

Densities of phases:- Densities can be enhanced by addition of oil when oil is an external phase. Temperature Fluctuations:- Elevation

in temperature can cause instability, even degradation of drugs.

Phase Inversiono/w w/o OR w/o o/w

It can be done by two ways:-

i. Changing chemical nature of emulsifierii. Altering the phase volume ratio.

PHYSICAL STABILITY

OFEMULSIONS

Chemical Physical

Study of stability

It includes study of: Degradation of Active drug, Emulsifiers, Preservatives, Anti-oxidants, etc

It includes study of: Shelf life, obtain its form on moderate shaking, etc

1.Extent of phase Separation:

Commercially used method, by studying the phase separation.It can be detected simply by breaking of the emulsions.Other factors are coalescence and creaming…

2.Globule size distribution:

Microscopic evaluation of Globule size gives idea of stability of an emulsion.If the globule size are larger, it indicates the aggregation of globules and due to which the emulsion is not stable.

It is studied by centrifugation method:The Emulsion is kept in centrifuge and then plot of Depth of Oil in centrifuge Vs Time (in seconds) is plotted. As the depth increases the stability is less..

PREPARATIONOF

EMULSION• Selection of oil phase• Selection of Aqueous phase• Selection of Emulsifying agent• Stability considerations of emulsion

A) Small scale preparation 1. Wet Gum (English) method2. Dry Gum (Continental) method

B) Large scale preparation

Large scale preparation

Method is similar to that of small scale. Only the difference is the agitation in small scale is done by trituration and in large scale it is done by various mixtures such as: Agitator, Mechanical mixtures, Propellers, Turbine mixers, colloid mills, Ultrasonic devices.

TextbookOf PHYSICALPHARMACY

C V SSUBRAHMANYAM

-by

Thank YOU