Inprocess quality control of emulsions

IPQC

1. INPROCESS QUALITY CONTROL OF EMULSIONS BY: CH. SANDHYA ASST. PROFESSOR DEPT OF PHARM. ANALYSIS

2. 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.

3. 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 micro emulsions(0.01μm) fine emulsions(0.25 to 25μm)

4. Instability of emulsions

5. 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

6. 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

7. 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

8. 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.

9.  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

10. IPQC tests for emulsions Appearance Clarity testing pH value Viscosity Rheology Drug content uniformity Particle size distribution Densities of phases

11. 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

12. 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 .

13. 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

14.   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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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

20. 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.

21.   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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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 .

27. 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.

28. 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

29. 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.

30.   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.

31.  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.