5. Biphasic Liquid Dosage Forms-Emulsion.pptx

Pharmaceutics II

1. Pharmaceutics II (0811) Chapter – 6 . Prof. Vaishali P. Argade Lecturer in PRES, Institute of Pharmacy, Loni Email:[email protected] Mobile:[phone] Biphasic Liquid Dosage Form EMulsion

2. Learning Outcomes After completion of this chapter, you will be able to: Define the Emulsion as biphasic liquid dosage form. Understand types, qualities & need of good emulsion 3. Understand the Classification, formulation, method of preparation, container, storage & stability condition required for biphasic liquid dosage forms emulsion.

3. Definition: emulsion are heterogeneous, biphasic, thermodynamically unstable liquid system in which one phase is dispersed as globules (Discontinuous/dispersed /Internal phase) in to another phase (continuous/external phase /Dispersion medium) & stabilized by emulsifying agent. The globules size of emulsion varies from 0.25 to 25 micrometer in diameter.

4. Advantages of emulsion Medicine having unpleasant taste & odour can be made in emulsion. It provides protection against oxidation & hydrolysis Various external preparation like c ream, lotion, aerosol are formulated in emulsion. The sterile stable intravenous emulsion also formulated There should be uniform dispersion of internal phase in external phase. The internal phase should not aggregate. The internal phase should not cream up or cream down & should be redispersible . The emulsion should retain in its original type without phase inversion. Qualities of good emulsion

5. Types of suspension: 1. O/W (Oil in water) type 2. W/O (Water in oil) type Sr. No. O/W type Sr. No. W/O type 1 Oil is disperse in water 1 Water is disperse in oil 2 External phase is water so stain by Methylene blue 2 External phase is oil, so stain by scarlet red III 3 Miscible with water 3 Miscible with oil 4 Good conductor of electricity 4 Bad conductor of electricity 5 Ex. Liq. Paraffin emulsion 5 Ex. Oily calamine lotion

6. Classification of Emulsion

7. Identification of type of emulsion Dilution Test Dye Test Conductivity Test Fluorescence Test

8. 1. Dilution Test The type of emulsion can identify on the basis of dilution test Emulsion is diluted with water if it remain stable it is O/W type emulsion. When emulsion break it is W/O type. O/W emulsion easily diluted with water & W/O emulsion easily diluted with oil

9.   2. Dye Test W hen an emulsion is mixed with a oil soluble dye such as scarlet red dye and observed under the microscope. If the continuous phase shows red color and dispersed globules shows colorless means W/O type of emulsion. If the dispersed globules shows red color and continuous phase colorless , means O/W type of emulsion

10. 3. Conductivity Test: Water is good conductor of electricity but oil is not. This test perform by dipping pair of electrode connected by a bulb in the emulsion. If the bulb glow t hat means O/W type of emulsion I f not glow that means W/O type of emulsion

11. 4. Fluorescence Test: Certain fixed oil has property of fluorescing in presence of UV radiation on microscopic observation. If continuous phase give fluorescence that means W/O type of emulsion. If dispersed globules gives fluorescence that means O/W type of emulsion .

12. Formulation of Emulsion Emulsifying agents/ Emulgent /Emulsifiers The emulsifying agent reduces the interfacial tension between the two phases i.e. oily phase & aqueous phase & thus make them miscible with each other & form a stable emulsion. Griffin provide a useful method to calculate the balanced mixture of emulsifying agent called as hydrophile lipophile balance (HLB method). Every emulsifying agent given a number on HLB scale, which is divided in to 18 units. Emulgent with high number (8-18) indicates hydrophilic properties & produce o/w type of emulsion. Emulgent with Lower number (3-6) represent lipophilic property & produce w/o type of emulsion.

13. Table: HLB values & its applications

14. Ideal properties of Emulsifying agents It should be able to reduce the interfacial tension between the two immiscible liquids. It should be physically and chemically stable , inert and compatible with the other ingredients of the formulation. It should be non irritant and non toxic It should be able to produce and maintain the required viscosity of the preparation. It should be able to form a coherent film around the globules of the dispersed phase and should prevent the coalescence of the droplet of the dispersed phase.

15. Classification of Emulsifying agents

16. I. - 1)Natural emulsifying agents from vegetable sources: It includes gums & mucilaginous substances. Anionic in nature & produce o/w type of emulsion. It need suitable preservatives. Acacia: Use in i nternal preparations. Prepared emulsion are attractive in appearance & stable at pH 2-10. To make more stable emulsion other emulsifying agents are used in combination. B. Tragacanth - Alone it is rarely used because it produces very thick & coarse emulsion. More effective in combination with acacia. C. Agar I t is rarely used because it produces very thick & coarse emulsion. 2% mucilage used as emulsifier.

17. Pectin- 1% mucilage is used E. Starch- It is rarely used because it produces very thick & coarse emulsion. It is used to prepared the enemas F. Irish moss- Used as a thickening agent 3% solution is generally used. I. - 2)Natural emulsifying agents from animal sources: Wool fat: Use in external preparations. Produces O/W type of emulsion as it absorb 50 % of water. B. Egg yolk : Use in internal preparations . Need proper preservation & storage in refrigerator. Used in 12-15% conc. Gelatin- Used in 1% conc. Need proper preservation

18. II. Semisynthetic polysaccharide Methyl cellulose: It is cellulose derivative. Used as suspending, thickening & emulsifying agent in 2% conc. B. Sodium Carboxy Methyl cellulose : Used in 0.5 – 1% conc. Soluble in cold & hot water III. Synthetic emulsifying agents A. Anionic: Ex.  various alkali soaps, metallic soaps, sulphated alcohols & sulphonate are used as an anionic emulsifying agent. soap emulsion are used for external preparation. It produces o/w type of emulsion B. Cationic:   Quaternary ammonium compound such as benzalkonium chloride benzthionium chloride, cetrimide used as cationic emulsifying agent.  They bear positive charge and are used in external preparation such as lotion and creams.

19. C. Non ionic : Ex. Glyceryl esters such as glyceryl monostearate , sorbitol, fatty acid, Ester.     They are stable over wide range of PH IV. Inorganic emulsifying agent Ex. Milk Of Magnesia (10-20%), Magnesium Oxide (5-10%) Magnesium Trisilicate , Magnesium Aluminium Silicate(1%) Bentonite (5%) V. Alcohols Carbo waxes -mainly used in the preparation in ointment and cream B. cholesterol - they are used to stabilize the emulsion. They are used with other emulsifying agent C. Lecithins - form w/o type of emulsion. T t is rarely used because it darken its colour when exposed to light and get easily oxidized.

20. 2. Preservation o f Emulsion Emulsion need preservation. It may causes unpleasant odour , taste & discoloration. Preservatives used like benzoic acid, methyl paraben , propyl paraben , chloroform, chlorocresol , cetrimide , phenyl nitrate. Contamination of emulsion may occur due to following reasons. Equipment used in preparation are carelessly cleaned. By using contaminated emulsifying agent The ratio of oil & Water is not proper Using not properly store deionized or purified water pH of the preparation Following steps can be taken to minimized it Used cleaned equipment Used ingredient of standard quality Maintain the prescribed ratio of oil, water & Gum Used freshly boiled & cooled water Use container & closure of good quality Maintain the prescribed pH of preparation.

21. 3. Antioxidants Fats, emulsifying agent undergoes oxidation by atmosphearic oxigen . Antioxidants used tocopherol , gallic acid, propyl gallate , ascorbic acid . Qualities of Antioxidants It should be readily soluble in the dispersion medium. Effective at low conc. Nontoxic, non irritants Compatible with other ingredients Colourlee , odourless , tasteless. 4. Flavours Vanillin used for liquid paraffin emulsion. Benzaldehyde for cod liver oil emulsion

22.   1. Dry Gum Method 2. Wet Gum Method 3. Bottle Method 4. Other Methods: Hand homogeniser Silverson mixer homogeniser Table shows proportion of oil, water & gum acacia required for different type of oils. Preparation of Emulsion

23.   1. Dry Gum Method In this method the oil is first triturated with gum with a little amount of water to form the primary emulsion. The trituration is continued till a characteristic ‘clicking’ sound is heard and a thick white cream is formed. Once the primary emulsion is formed, the remaining quantity of water is slowly added to form the final emulsion. Oil + Gum Acacia Triturate Smooth cream + Water Triturate to produce white cream or produces clicking sound Primary emulsion form Remaining quantity of water to produce final emulsion

24. Prepare emulsion using dry gum method Rx Arachis oil 50ml Purified Water add to 200ml Make a emulsion Procedure: Calculate oil : Water : Gum ratio 4 : 2 : 1 50 : 25 : 12.5 2. Prepare using dry gum method

25. 2. Wet Gum Method As the name implies, in this method first gum and water are triturated together to form a mucilage. The required quantity of oil is then added gradually in small proportions with thorough trituration to form the primary emulsion. Once the primary emulsion has been formed remaining quantity of water is added to make the final emulsion. Water + Gum Acacia Triturate Smooth cream + oil Triturate to produce white cream or produces clicking sound Primary emulsion form Remaining quantity of water to produce final emulsion

26. Prepare emulsion using Wet gum method Rx Arachis oil 50ml Purified Water add to 200ml Make a emulsion Procedure: Calculate oil : Water : Gum ratio 4 : 2 : 1 50 : 25 : 12.5 2. Prepare using wet gum method

27. 3. Bottle Method This method is employed for preparing emulsions containing volatile and other non-viscous oils. Both dry gum and wet gum methods can be employed for the preparation . In this method, oil or water with gum acacia added at once in the bottle& is shaken vigorously to form the primary emulsion. More of water is added in small portions with constant agitation after each addition to produce the final volume. Oil/Water + Gum Acacia Shake in bottle vigorously Primary emulsion form Remaining quantity of water to produce final emulsion

28. 4. Other Methods: Various blenders & homogeniser are used for emulsion preparation Principle: Large globules in coarse emulsion are broken in to smaller globules by passing them under narrow orifice. Hand homogeniser , Silverson mixer homogeniser

29. Stability of Emulsion An emulsion is said to be stable if it remains as such after its preparation , that is the dispersed globules are uniformly distributed through out the dispersion medium during its storage. The emulsion should be chemically stable and there should not be any bacterial growth during it shelf life. following changes occures during the storage of an emulsion: Cracking Creaming Phase inversion

30. 1. Cracking  Cracking means the separation of two layers of disperse and continuous phase, due to the coalescence of disperse phase globules which are difficult to redisperse by shaking . Cracking may occurs due to following reasons :- i. By addition of emulsifying agent of opposite type ii. By decomposition or precipitation of emulsifying agent iii. By addition of common solvent iv. By microorganisms v . Change in temperature vi . By creaming

31.   2. Creaming   Creaming may be defined as the upward movement of dispersed globules to form a thick layer at the surface of emulsion. Creaming is temporary phase because it can be re-distributed by mild shaking or stirring to get again a homogenous emulsion. The factors affecting creaming are described by stoke’s law: V = 2r2 (d1-d2) g/9 η Where, V= rate of creaming r=radius of globules d1 = density of dispersed phase d2 = density of dispersion medium g= gravitational constant η = viscosity of the dispersion medium

32. Radius of globules: Rate of creaming directly proportional to Radius of globules. Larger globules size more will be the creaming & Smaller globules size lesser will be the creaming. Hence homogenisers is used. b. Difference in density of disperse phase and continuous phase: Rate of creaming depends upon the Difference between the density of disperse phase and continuous phase. Greater difference more will be the creaming. c. Viscosity of dispersion medium : Rate of creaming inversely proportional to the Viscosity of dispersion medium. Viscosity can be increased by adding tragacanth & methyl cellulose. But too much viscosity is undesirable because it may become difficult to redispersed the settle material. d. Storage condition: Store in cool place because rise in temp. reduces the viscosity which may leads to creaming.

33. 3 ) Phase inversion :- Phase inversion means the change of one type of emulsion into other type, that is oil in water emulsion changes into water in oil type and vice-versa . It may be due to; By the addition of an electrolyte By changing the phase-volume ratio By temperature change By changing the emulsifying agent The phase inversion can be minimized by keeping concentration of disperse phase between 30 to 60 % , storing the emulsion in cool place and using a proper emulsifying agent in adequate concentration .

34. Storage of Emulsion It should be store in cool place & packed in comparatively wide mouth amber color glass bottle for its easy removal Label required is shake well before use.

35. Questions????? Sr.no. Questions Q.1 Define the term emulsion. Write advantages of emulsion. Q.2 Write short note on HLB Value. Q.3 Explain creaming of emulsion using Stroke’s law. Q.4 How will you distinguish between w/o & o/w type emulsion? Q.5 Write the test to identify the type of emulsion. Q.6 Write the different methods of preparation of emulsion.

36. References Pharmaceutics II By R. M. Mehata , Vallabh Prakashan , Third edition, 2010. Pharmaceutics-2 (Dispensing Pharmacy) By Dr. G.K.Jani , B.S.shah Prakashan , 10 th edition, 2011-2012. Introduction to Pharmaceutics-II By A.K.Gupta & S.S. Bajaj, CBS Publishers & Distributors, 4 th edition,2000. MSBTE board Annual question paper, https ://msbte.org.in 38 By- Ms. Argade V.P.

37. Thank you………..