INPROCESS QUALITY CONTROL OF EMULSIONS

BY:CH. SANDHYAASST. PROFESSORDEPT OF PHARM. ANALYSIS

EMULSIONS

• Emulsion: Systems consisting of at least two immiscible

liquid phases, one of which is dispersed as small globules in

the other liquid phase.

• The globule diameter may range from 0.1 to100 μm.

• Emulsions are thermodynamically unstable systems.

Emulsions are also called as heterogeneous systems ,or

more precisely biphasic systems.

•Classification

1)Based on nature of dispersed phase

a)oil-in-water(o/w)

b)water-in-oil(w/o)

2)Based on the globule size

a) micro emulsions(0.01μm)

b) fine emulsions(0.25 to 25μm)

Instability of emulsions

Instability of emulsions

•Flocculation

• Neighbouring globules come closer to each other and

form colonies in the external phase.

•This is the initial stage that leads to instability

• The extent of flocculation of globules depends on

a)globule size distribution

b)charge on globule surface

c)viscosity of external medium

• Creaming

• Creaming is the concentration of globules at the top or

bottom of the emulsion.

• The floccules move either upward or downward leading to

creaming.

• It can be observed by a difference in colour shade of the

layers.

• Creaming is influenced by a)globule size b)viscosity of the

dispersion medium c)differences in the densities of

dispersed phase and dispersion medium

• Coalescence

•Coalescence is followed by creaming stage.

•In this process the emulsifier film around the globules is

destroyed to a certain extent.

• This step can be recognised by increased globule size and

reduced number of globules.

• Coalescence is observed due to a)insufficient amount of

the emulsifying agent b)altered partitioning of the

emulsifying agent c)incompatibilities between emulsifying

agents

•Breaking

•This is indicated by complete separation of oil and

aqueous phases.

•It is an irreversible process that is simple mixing fails to

resuspend the globules into an uniform emulsion.

• In breaking, the protective sheath around the globules is

completely destroyed.

• 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

IPQC tests for emulsions

Appearance

Clarity testing

pH value

Viscosity

Rheology

Drug content uniformity

Particle size distribution

Densities of phases

Phase volume ratio

Charge of electrical double layer

Physical properties of interface

Temperature fluctuations

Quality control of water

Breaking or cracking

Compatibility of product with container-closure system

VISUAL INSPECTION :

With visual inspection, the ingredients and the final

products are carefully examined for purity and for

appearance .

Physical appearance of products for patient adherence and

compliance is critical so it should be: Good looking Elegant

in appearance .

VISCOSITY

•As the viscosity increases flocculation of globules will be

reduced .simultaneously the Brownian movement of

globules will also be hindered leading to creaming.

•Due to this antagonistic effect an optimum viscosity is

desirable for good stability.

• Viscosity can be measured by

• a)cup and bob viscometer

• b)cone and plate viscometer

PARTICLE SIZE

• As the globule size is reduced they tend to exhibit

Brownian movement.

• According to stokes law the diameter of the globule is

considered as a major factor in creaming of emulsion.

• The rate of creaming decreases four folds when the

globule diameter is halved.

• So it is necessary to choose the optimum globule size for

maximum stability.

PARTICLE SIZE DISTRIBUTION

• Globules of uniform size impart maximum stability.

In such emulsions globules pack loosely and globule to

globule contact is less.

•Globule distribution is effected by viscosity, phase volume

ratio, density of phases etc.

An optimum degree of size distribution range should be

choosen to achieve maximum physical stability.

GLOBULE SIZE DETERMINATION

•Microscopic examination of globule size distribution

analysis is an useful tool to evaluate the physical stability.

PHASE VOLUME RATIO

•In an emulsion the relative volume of water to oil is

expressed as phase volume ratio.

• In general most medicinal emulsions are prepared with a

volume ratio of 50:50.

•This proportion brings about loose packing of globules.

The upper limit 74% of oil can be incorporated in an

emulsion but this may lead to breaking of the emulsion.

This value is referred to as critical point of phase volume

ratio.

•Critical point is defined as the concentration of internal

phase above which the emulsifying agent cannot produce a

stable emulsion of the desired type.

PHASE INVERSION

•The emulsion is checked for phase inversion which means

a change of emulsion type from o/w to w/o or vice versa.

EXTENT OF PHASE SEPARATION

•The practical and commercial aspect of stability is the

study of phase separation.

•This is quick method and can be applied for poorly formed

and rapidly breaking emulsions.

•Separation of phases is visible after a definite period of

time, though the signs of instability begin quite early.

CHARGE OF ELECTRICAL DOUBLE LAYER

•When ionic type of emulsifier is employed, the electrical

double layer(interface between oil and water) possesses

charge.

•The repulsive forces, due to like charges on the surface of

the globules prevent the flocculation of globules

UNIFORMITY OF MASS

•Weigh individually the contents of 20 containers, empty it

completely, and determine the average mass.

•Not more than 2 of the individual masses deviate by more

than 10 per cent from the average mass and none deviates

by more than 20 per cent.

PHYSICAL PROPERTIES OF INTERFACE

• The interfacial film of the emulsifier is responsible for

enhancing the stability of the product.

• The film should be elastic enough to form rapidly as soon

as droplets are produced. This behaviour facilitates the

production of emulsion.

• Similarly on moderate shaking the emulsion should be

reconstituted.

• After manufacture the film should be tough so that

coalescence of globules can be prevented.

•So suitable emulsifying agents such as surfactants should

be selected to achieve the above film properties at the

interface.

DENSITIES OF PHASES

•By adjusting the density of the phases to the same value

we can increase the stability of emulsion.

•Oil phase density can be enhanced by adding brominated

oil when the oil is an external phase.

DILUTION TEST:

•The emulsion is diluted with water. In case the emulsion

remains stable after its dilution, it is o/w emulsion.

•The w/o emulsion breaks on its dilution with water but

remains stable when diluted with oil.

DYE TEST:

•The scarlet red dye is mixed with the emulsion. Place a

drop of the emulsion on a microscopic slide, Cover it with a

cover- slip, and examine it under a microscope. If the

disperse globules appear red and the ‘ground ’ colourless,

the emulsion is o/w type.

•The reverse condition occurs in w/o type emulsion i.e.,

the disperse globules appear colourless in the red ‘ground’.

CRACKING TEST:

•By addition of emulsifying agent of opposite type : Soaps

of monovalent metals produce o/w type emulsions

whereas soaps of divalent metals produce w/o type

emulsions.

• But the addition of monovalent soap to a divalent soap

emulsion or a divalent soap to a monovalent soap

emulsion leads to cracking of emulsion.

•By decomposition or precipitation of emulsifying agents:

When an acid is added to an alkali soap emulsion

(turpentine liniment), it causes the decomposition of an

emulsifying agent and thus leads to cracking of an

emulsion.

•Similarly, when sodium chloride is added to sodium or

potassium soap emulsion, it leads to the precipitation of

emulsifying agents and thus cracking of emulsion take

place.

TEMPERATURE FLUCTUATIONS

•Elevated temperatures alter the partition characteristics of

the emulsifiers and preservatives results in instability.

•Temperature also enhances the chemical degradation of

drugs and other ingredients.

•At lower temperature the aqueous phase may contain ice

crystals which rupture the interfacial film and break the

emulsion.

• So care should be taken to prevent temperature

fluctuations during manufacture and storage.

COMPLETION STAGE

At the completion of manufacturing process as well as in-

process stages, actual yields are checked against theoretic

value and the representative sample are withdrawn for

laboratory testing by the control inspector according to the

predetermined sampling plan.

RECORD AND REPORT

The batch production records and other needed

documents are then delivered to the quality control office

together with the withdrawn samples of the products.

PACKAGING MATERIAL CONTROL

• Packaging material should not interact physically or

chemically with the finished product to alter the strength,

quality or purity beyond specified requirements.

• The following features are to be considered in developing

container specifications:

• Properties of container tightness

•Moisture and vapour tightness regardless of container

construction

•Compatibility between container and product

•Toxicity and chemical/physical characteristics of materials

needed in container construction.

•Physical or chemical changes of container upon

prolonged contact with product

LABELS CONTROL

•Production control issues a packaging form that carries

• The name of the product, Item number, Lot number,

Number of labels, Inserts, Packaging material to be used,

Operation to be performed, Quantity to be packaged.

• A copy of this is sent to the supervisor of label control,

who in turn counts out the required number of labels.

•Conclusion

•IPQC tests are carried out during the manufacturing to

ensure stable, safe and quality product.

• References

• Lachman L,Lieberman H,The Theory andPractice of

Industrial pharmacy;3rdedition,page number-810 to 835.

• C.V.S.Subrahmanyam, Text book of Physical

Pharmaceutics,page number-195 to 203,366to 423.

• Encyclopedia volume-6 page number 3105-3107.