EMULSION: EMULSION Prepared By : Mr. Naresh Rajgor, Assistant Professor, M.P. Patel College of Pharmacy, Kapadwanj EMULSION : EMULSION Definition: “Emulsion is the biphasic liquid dosage forms in which two immiscible liquids are made miscible by using emulsifying agents. It contain one disperse phase and other is continuous phase. OR It is thermodynamically unstable system consisting of at least two immiscible liquid phases one of which is dispersed as globules (the dispersed phase) in the other liquid phase (the continuous phase) stabilized by presence of emulsifying agent. Ex: Milk PowerPoint Presentation: Types of emulsion: Oil in water (O/W): (Oral use) Water in Oil (W/O): (External use) Micro emulsion (transparent emulsion): The property of transparency is due to the small particle size of the dispersed phase (0.05 microns). Double Emulsion (Multiple emulsion): O/W/O W/O/W It can be prepared by proper selection of H.L.B. values. 5. Nano Emulsion DIFFERENCE BETWEEN O/W AND W/O EMULSIONS:: DIFFERENCE BETWEEN O/W AND W/O EMULSIONS: (o/w) (w/o) Water is the dispersion medium and oil is the dispersed phase Oil is the dispersion medium and water is the dispersed phase non greasy and easily removable from the skin greasy and not water washable used externally to provide cooling effect e.g. vanishing cream used externally to prevent evaporation of moisture from the surface of skin e.g. Cold cream preferred for internal use as bitter taste of oils can be masked. preferred for external use like creams. PowerPoint Presentation: ( W/O ) ( O/W ) PowerPoint Presentation: APPLICATION OF EMULSION: Objectionable taste can be made more palatable and administered more conveniently. Oily material for topical use have greater acceptance if emulsified as a lotion or cream In emulsified state material have good penetration and spreading ability. Emulsification of oils enhances the rate and extent of their absorption of some drugs like insulin, heparin. Emulsion type bases are more effective in releasing medicaments and are easily washed off as compared to oleaginous base. W/O emulsions are employed more widely for treatment of dry skin and emollient applications. The bad taste of some water soluble substance canbe masked by emulsification. Parenteral emulsion can be formulated for lipid nutrients. Determination of emulsion type: Determination of emulsion type Test Observation Comments Dilution Test (Miscibility) Emulsion can be diluted with only external phase Useful for liquid emulsions only o/w emulsion can be diluted with water. w/o emulsion can be diluted with oil. PowerPoint Presentation: Test Observation Comments Dye Test (Staining) Water soluble solid dye (amaranth) shows color only with O/W emulsion, while sudan -III or Scarlet red Dyes readily tint a W/O emulsion. May fail if ionic emulgents are present. CoCl 2 Filter Paper Filter paper impregnated with CoCl 2 dried (Blue) changed to pink when O/W emulsion is added. PowerPoint Presentation: 4. Fluorescence Test Many oils when exposed to U.V. light fluorescence. O/W exhibit dot patter. W/O entire field fluoresces. Not always applicable 5. Direction of creaming test If emulsion creams are upward the emulsion is O/W type. If the emulsion creams are downward it is W/O type emulsion. PowerPoint Presentation: 6. Conductivity Test Water conduct an electric current wile oils do not. Fails in non ionic O/W emulsion PowerPoint Presentation: Theory of Emulsion: 1 . Surface tension theory: Theory states that an emulsion results when substance is introduced to lower the interfacial tension between two immiscible liquids. A surface active agent which lowers the surface tension and act as stabilizing force for emulsion. 2. Surface adsorption: Adsorption is the concentration of any substance at the surface of another. Foe example water is a liquid to which a solid soap sodium oleate has been added. PowerPoint Presentation: Here both cohesive (attraction between like molecules) and adhesive forces (attraction between unlike molecules) are operative. If the adhesive force (liquid-liquid or solvent) leading to an increase in the surface tension of the solvent. If adhesive forces are weaker than cohesive force, leading to the concentration of solute near periphery of the liquid solvent and resulting in the reduction of surface tension. 3. Oriented-Wedge Theory: It explains the emulsion formation on the basis of selective solubility of surfactant. Surfactant possesses a polar and nonpolar group. It orients itself in such a way that the polar group faces water and non polar group faces the oils. Ex: Soap PowerPoint Presentation: 4. Plastic film theory (Interfacial film theory) According to this theory, the emulgent is deposited upon the surface of the individual droplets of the dispersed phase in the form of plastic film monomolecular. This film prevents the contact and coalescence of the dispersed liquid. Thus action of emulgent is purely mechanical and does not depend upon surface tension. PowerPoint Presentation: Selection of Phase. Choice of emulgents Other additives. 1. Selection of phase Out of two phase, one phase is fixed and that is water. The oily phase is selected on following consideration. -Toxicity if oil -Consistency desired. -Possible chemical incompatibility. Normally for oral emulsion, mineral oils and edible vegetable oils are used. FORMULATION OF EMULSION PowerPoint Presentation: Phase volume ratio: It will be determined by: A. Dosage requirement: For O/W emulsion, 31-45% water. For W/O water less than 25% B. Consistency desired. Concentration of internal phase affects its viscosity upto 75%.means concentration of an internal phase increase the viscosity. PowerPoint Presentation: 2. Choice of emulgent Selection based on Toxicity Chemical incompatibility The cost Types of emulsion desired Shelf-life stability. For a good emulsion consider the H.L.B. of oil phase, H.L.B. of emulgents and H.L.B. desired. A blend of emulgents give better emulsion than single emulgent . PowerPoint Presentation: 3. Other Additives: Consistency: It depends upon concentration of emulgent and phase volume ratio. B . Antimicrobials: AS emulsion contain carbohydrates, proteins, sterol, which readily support the microbial growth. So inclusion of antimicrobial is necessary part of formulation. Benzoic acid - Vanillin - Sorbic acid - Methyl paraben -BKC - Propyl Paraben PowerPoint Presentation: C . Antioxidants: Emulsified liqids are subject to autooxidation upon exposure to air. - gallic acid -BHA -BHT - Tocopherol - Propyl gallate . D. Organoleptic Agents like colors, flavors and sweeteners. The addition of salts, syrups and alcohol must be consider carefully in preparation because they may break the emulsion, so they can use by mixing and diluting these agents with water. Proportions of Oil, Water and Gum required for formation of primary emulsion:: Proportions of Oil, Water and Gum required for formation of primary emulsion: Proportions of Type of oil oil Water gum gum Fixed oil 4 2 1 Mineral oil 3 2 1 Volatile oil 2 2 1 PREPRATION OF EMULSION: PREPRATION OF EMULSION Dry Gum Method (Continental Method) This method is also called as 1:2:4 or 4,2,1, these figure represents the proportion of oils, water and gum. Oil Water Gum 4 2 1 This ratio is used for the preparation of primary emulsion. PowerPoint Presentation: Emulsifier is triturated with the oil in perfectly dry porcelain mortar water is added at once triturate immediately, rapidly and continuously (until get a clicking sound and thick white cream is formed, this is primary emulsion) the remaining quantity of water is slowly added to form the final emulsion PowerPoint Presentation: With linseed oil or liquid paraffin the ratio of primary emulsion is Oil Water Gum 3 2 1 PowerPoint Presentation: 2. Wet Gum Method: (English or American Method) In this method, the proportion of gum, water and oil remains same as that of dry gum, but the procedure is differ. triturate gum with water in a mortar to form a mucilage oil is added slowly in portions the mixture is triturated after adding all of the oil, thoroughly mixed for several minute to form the primary emulsion Once the primary emulsion has been formed remaining quantity of water is added to make the final emulsion. PowerPoint Presentation: 3. Bottle Method OR Forbes Bottle Method - It is extemporaneous preparation for volatile oils or oil with low viscosity. gum + oil (dry bottle) Shake water (volume equal to oil) is added in portions with vigorous shaking to form primary emulsion gum + oil (dry bottle) Shake remaining quantity of water is added to make the final emulsion PowerPoint Presentation: Types of oils Examples Qty for primary emulsion Oil Water Gum 1. Fixed oils Almond oil Arachis oil Castor oil Cod liver oil 4 2 1 2. Mineral oil Liquid paraffin 3 2 1 3. Volatile oil Turpentine oil Cinnamon Peppermint 2 2 1 4. Oleo-resin Male fern Extract 1 2 1 STABILITY OF EMULSION: STABILITY OF EMULSION CREAMING OR SEDIMENTATION AGGREGATION AND CO-ALESCENCE (CREAKING OR BREAKING OF EMULSION) PHASE INVERSION MICROBIAL GROWTH PowerPoint Presentation: 1.CREAMING: Creaming is the upward movement of dispersed droplets relative to the continuous phase, while sedimentation is the downward movement of particles. In O/W type of emulsion, as oils are lighter, creaming will therefore take place. Creaming or sedimentation produces non-homogeneous system. Creaming or sedimentation may facilitate the coalescence and hence breaking of emulsion. Creaming is not permanent phenomena. Creamed emulsion made homogeneous by shaking. It is less serious. PowerPoint Presentation: Creaming is governed by Stoke’s law, V= d 2 ( 1-2 ) ______ 18 From the equation, it points out the factor that influence the rate of creaming/sedimentation. d. Diameter of globules Viscosity Differences in density of two phase is more, lesser the stability of emulsion. Temperature: Lowering the temperature increases the viscosity and hence increase the stability. so store in cool place. Strategies to reduce creaming:: Strategies to reduce creaming: Principle Method Reduce droplet size (r) Homogenizer Reduce density difference (Δ p) Add weighting agent are oils that, have a density greater than the density of water Increase continuous phase viscosity ( η) Add thickening or gelling agent e.g. methylcellulose PowerPoint Presentation: 2 . Aggregation and coalescence: These are more serious then creaming. In aggregation, the dispersed droplets come together but do not fuse. In coalescence, because of the complete fusion of droplets ultimate separation of two immiscible phase, creaking takes place. Coalescence start from aggregation. Aggregation is to some extent reversible and upon shaking form emulsion. Coalescence leads to breaking of emulsion and it will not restore upon shaking. PowerPoint Presentation: 3. Phase Inversion: In phase inversion o/w type emulsion changes into w/o type and vice versa. It may be brought about by: 1- the addition of an electrolyte e.g. addition of CaCl2 into o/w emulsion formed by sodium stearate can be inverted to w/o. 2- by changing the phase volume ratio 3- by temperature changes. - Phase inversion can be minimized by: 1- using the proper emulsifying agent in adequate concentration. 2- keeping the concentration of dispersed phase between 30 to 60 %. 3- storing the emulsion in a cool place. 4. MICROBIAL GROWTH: 4. MICROBIAL GROWTH Contamination due to microorganisms can result in problems such as: 1- color and odor change 2- gas production 3- hydrolysis 4- pH change 5- breaking of emulsion e.g. methyl, propyl and butyl parabens e.g. organic acids such as ascorbic acid and benzoic are used as a preservative to prevent the microbial growth. EVALUATION OF EMULSION: EVALUATION OF EMULSION SIZE DISTRIBUTION ANALYSIS By –Microscopic method --Electron counting device. Rate of phase separation Centrifugation may be used as a means of speeding up the separation process. Viscosity and Rheological Study. Measurement of di-electric constant. Conductivity measurement Influence of temperature Microwave irridiation Micro electro phoretic measurement. Emulsifying agents used:: Emulsifying agents used: Hydrophile-Lipophile Balance (HLB) : Hydrophile-Lipophile Balance (HLB) HLB: the ratio between the hydrophilic portion of the molecule to the lipophilic portion of the molecule. The higher the HLB of an agent the The more hydrophilic it is. Spans are lipophilic have low HLB. Tweens are hydrophilic have high HLB.