Emulsion

Emulsion, Types, Identification tests, Components, Emulsifying agents, Theories of emulsification, Formulation, HLB system, Stability Issues, Drug release in GIT, Advantages, Disadvantages

1. Emulsions Introduction, Types, Formulation, Stability

2. Introduction An emulsion is a two phase system consisting of two immiscible liquids, one of which is dispersed as finite globules in the other. An emulsifying agent is needed to join the phases.

3. Types OF EMULSION Oil in Water, Water in Oil emulsions

4. Types Major types of emulsions are: Oil in Water emulsions : Oil is dispersed as small globules in water. Such emulsions are usually used for oral administration as well as for IV and topical uses. Water in Oil emulsions : Water is dispersed as small globules in oil. Such types of emulsions are usually used externally. Other types include Multiple Emulsions and Micro Emulsions.

5. Identification Tests to determine type of emulsion

6. Identification tests Some tests for the identification of emulsion system are given below: Dilution Test: If we add more of the continuous phase, the emulsion is only diluted and no other effect occurs on it. Conductivity Method: O/W emulsion can conduct electricity as water is a good conductor of electricity. Dye Solubility Test: Water-soluble dye is added to it and examined under microscope.

7. Identification tests Cobalt Chloride Test: CoCl 2 turns from blue to pink when exposed to water.  Fluorescence Test: Many oils have the property to show florescence under UV light. Creaming Direction Test: If the densities of both water phase and oil phase are known, we can identify the emulsion type on the basis of creaming direction.

8. Emulsifying agents Introduction, Types

9. Emulsifying agents They are very important for the stability of emulsions. An ideal emulsifying agent has the following properties. Surface Activity : It should have the ability to reduce the surface tension to less than 10 dyne/cm. Charge Production : The emulsifier must form charges on the surface of the globules. It prevents coalescence. Viscosity Enhancement : The emulsifier should have the ability to increase the viscosity of the emulsion. Effectiveness : The emulsifying agents must be effective in smaller concentration.

10. Types of Emulsifiers Emulsifiers are classified as: Synthetic emulsifier Natural emulsifier Auxiliary emulsifier Finely divided solid emulsifiers

11. Synthetic Emulsifiers The synthetic emulsifiers are advantageous because they are non susceptible to the microbial growth; and a variety of emulsifiers may be obtained by modifications. The synthetic emulsifying agents may be classified into Non-Ionic & Ionic Emulsifiers.

12. Non-ionic Emulsifiers Non-ionic emulsifiers contain the largest group of emulsifying agents. The examples of Non Ionic Emulsifiers are Glycerol esters, Fatty acid esters, Sorbitan mono laurate, etc. The non-ionic emulsifiers are of great advantages because these are not affected by pH change or presence of strong electrolytes. The disadvantage is that preservatives having Phenolic or Carboxylic acid groups are inactivated by them.

13. Ionic Emulsifiers The ionic emulsifiers include: Anionic Emulsifiers : They are not suitable for oral use because of unpleasant taste and GIT irritant action. The examples of anionic emulsifiers are Alkali soaps, Metallic soaps, Sulphonates, etc. Cationic Emulsifiers : Cationic agents are weak emulsifiers. Example is Benzalkonium Chloride.

14. Natural Emulsifiers There are a lot of emulsifying agents that are derived from plants and animal sources. These substances are so much complex and have a variable chemical composition and thus they show a very wide change in the emulsifying properties. They can easily be destroyed by microorganisms. Examples are Acacia, Gelatin, lecithin, Cholesterol and wool fat, etc.

15. Auxiliary Emulsifiers Auxiliary emulsifiers are not capable to form a stable emulsions by themselves but when they combine with primary emulsifiers, they give a highly stable emulsion. Auxiliary emulsifiers are thickening agents and prevent the creaming and sedimentation and thus make the emulsion stable. Examples includes Tragacanth, Agar, etc.

16. Finely divided solids There are certain solid that acts as emulsifiers when they are ground to powder form. The examples of such solids are Bentonite, Magnesium hydroxide, Silica gel, etc.

17. Selection It should be non-toxic and non-irritant; physically and chemically compatible. It should not give any color, taste, or odor to the product. It should be capable of maintaining and producing the desired viscosity of the product.

18. hydrophilic-lipophilic balance system HLB value & its uses

19. HLB system It is a system having numerical values from 1 to 50, It tells us whether emulsifier is hydrophilic or lipophilic. HLB value can be determined as: HLB = 20 × If the HLB value is 3-8 then the emulsifier will be lipophilic. I f the HLB value is 8-18 then the emulsifier will be hydrophilic .  

20. HLB system HLB values of some emulsifiers

21. HLB system Advantages It helps to identify lipophilic or hydrophilic emulsifiers. Two emulsifiers can be blended to bring them at any HLB value. Disadvantages It does not tell required quantity of emulsifier. Different methods give different HLB value for the same emulsifier.

22. theories of emulsification Surface tension theory, Oriented-Wedge theory, Interfacial film theory

23. Emulsification When a liquid is broken into small droplets, the surface free energy also increases. Thus, the system separates into two phases due to coalescence of oil particles. Emulsifying agents reduce the interfacial tension between the two phases and form a stable interfacial film between them. Three theories of emulsification describe this phenomena.

24. Theories of Emulsification Surface Tension theory: Emulsifier lower the interfacial tension of the two immiscible liquids, reducing the repellent force between the liquids, and diminishing each liquid attraction for its own molecules. Oriented Wedge theory: Emulsifying agent orients itself in that liquid phase of an emulsion in which it is more soluble. It is based on Bancroft rule. Interfacial Film theory: Emulsifying agent is adsorbed at the interface between the oil and water, surrounding the droplets of the internal phase as thin layer of film. The tougher and more pliable the film, the greater will be the stability of the emulsion.

25. Preservation Antimicrobial preservatives, Antioxidants

26. Antimicrobial preservatives The preservative must be non-toxic, stable, cheap, broad spectrum, non ionized and chemically compatible. It should have acceptable taste, odor and color. It should be bactericidal. Examples are Benzyl alcohol, cetrimide, cresol, Phenol etc.

27. Antioxidants Autoxidation occurs by free radical reaction. It can be prevented by absence of oxygen, a free radical chain breaker by reducing agent. An antioxidant should be nontoxic, nonirritant, effective, soluble in the medium and stable. Antioxidants for use in oral preparation should be odorless and tasteless. Examples are Ascorbic acid, Sulphites, L-tocopherol.

28. Additives Colouring & Flavouring agents

29. Colouring & Flavouring agents Colour is rarely needed in an emulsion, as most have an elegant white colour and thick texture. Emulsions for oral use will usually contain some flavouring agent. 

30. Methods of preparation Dry Gum method, Wet Gum method, Nascent soap method

31. Wet Gum Method It is also known as English Method or American method. It is called wet gum method because the gum is wetted by water. All water soluble ingredients are dissolved in aqueous phase and oil soluble components are dissolved in oil. Then, dispersed phase is added gradually to the continuous phase and is stirred continuously. It is the easiest and most frequently used method.

32. Dry Gum Method It is also known as Continental Method. It is the process in which the dry gum is distributed in oil instead of water. The external phase is added to the internal phase. So, this can lead to the formation of W/O emulsion although the emulsifier is Hydrophilic.

33. Nascent Soap Method In this method, oil containing free fatty acids is added to water phase containing Ca(OH) 2 . This results in the formation of alkali soap.

34. Stability issues Flocculation, Coalescence, Creaming, Cracking, Phase Inversion

35. Major Stability Issues of Emulsions Flocculation, Coalescence, Creaming, Cracking, Phase Inversion

36. Flocculation It is the association of particle within an emulsion to form large aggregates. Interfacial film and individual droplets remain intact. So, these aggregates can easily be redispersed upon shaking. The reversibility of flocculation depends upon strength of interaction between particles as determined by: the chemical nature of emulsifier, the phase volume ratio, the concentration of dissolved substances, specially electrolytes and ionic emulsifiers.

37. Flocculation The extent of flocculation of globules depends on Globule size distribution : Uniform sized globules prevent flocculation. This can be achieved by proper size reduction process. Surface charge : A charge on the globules exert repulsive forces with the neighbouring globules. This can be achieved by using ionic emulsifying agent, electrolytes, etc. Viscosity : Flocculation can be prevented by increasing viscosity of external medium. This can be obtained by adding viscosity improving agents.

38. Creaming or Sedimentation Creaming and sedimentation is the concentration of globules at the top or bottom of emulsion. It is governed by Stokes’ law: V = Emulsion can be easily redispersed by shaking. Creaming is undesirable because: Increased possibility of coalescence Creamed emulsion is inelegant Risk of incorrect dose  

39. Creaming or Sedimentation Creaming can be reduced by: Reducing globule size by homogenization Increasing viscosity of dispersion medium Reducing the difference in density

40. Coalescence Coalescence is the fusion of two or more droplets of the disperse phase forming one droplet. Coalescence is an irreversible process and redispersion cannot be achieved by shaking. Coalescence is observed due to: Insufficient amount of the emulsifying agent Altered partitioning of the emulsifier Incompatibilities between emulsifiers

41. Coalescence Increasing the viscosity will reduce the potential for coalescence. It can be done by adding viscosity enhancing agents, increasing percentages of oil phase, decreasing the globule size, and using higher amounts of solid fats. Using emulsifying agents will decrease the potential for coalescence. Preventing extreme temperatures is important. Low temperature may lead to cracking of film. An increased temperature decreases the viscosity and increases number of collisions between droplets.

42. Cracking Cracking means the separation of disperse and continuous phase. Cracking may occurs due to following reasons: By addition of emulsifying agent of opposite type By decomposition or precipitation of emulsifying agent By addition of common solvent By microorganisms Change in temperature By creaming

43. Phase inversion This involves the change of emulsion type. The process is irreversible. Reasons of phase inversion can be: Increasing the dispersed phase concentration Adding substances that alter the solubility of emulsifier By changing the emulsifying agent Suppression of ionization for ionic surfactant Changing phase volume ratio Temperature changes

44. Phase inversion The phase inversion can be minimised by: Controlling concentration of disperse phase Storing the emulsion in cool place Using proper emulsifier in enough concentration

45. Drug release Factors affecting drug release in GIT

46. Major Factors The mechanism of drug release is dependent of several factors. First, drug solubilization characteristics are determining, principally the solubility in triglycerides which form the chylomicron core. Decrease in the particle size leads to a better rate of drug release. Oil nature also affect drug bioavailability. Vegetable edible oils increase drug absorption contrary to mineral oils. The oil chain length as well as the chain saturation seem to be important.

47. Major Factors The nature and quantity of surfactant present in the systems are very important. For absorption enhancement and oil digestion inhibition, surfactant with high HLB values are preferable. The charge effect of the emulsion influences oral bioavailability. Cationic surfactant improve the absorption profile due to electrostatic attraction.

48. Applications Advantages, Disadvantages

49. Advantages Emulsions are used to deliver water insoluble drugs. Oils having therapeutic effect can be administered. Emulsions can mask the bitter taste and odor of drugs. Emulsion gives stability to d rugs stable in oily phase. Emulsion give sustained release of the drug. E ssential nutrients can be emulsified and administered. IV emulsions of contrast media are used in diagnosis. Emulsions are used if patient cannot swallowing solid dosage forms. Emulsions protect drugs from oxidation or hydrolysis. Emulsions are used widely to formulate externally used products like lotions, creams, liniments, etc.

50. Disadvantages They are thermodynamically unstable. E mulsions may be difficult to manufacture. Storage conditions may affect stability. They are bulky, difficult to transport, and prone to container breakages. They are liable to microbial contamination which can lead to cracking. Uniform and accurate dose my not be achieved.