Emulsion
From Pharmpedia
racorla Emulsions are biphasic systems consisting of two immiscible liquids, one of which (the dispersed phase) is finely subdivided and uniformly dispersed as droplets throughout the other phase (the dispersion medium).
The dispersed phase is also called as the internal phase and the dispersion medium as external phase. These immiscible liquids are made miscible by adding a third substance known as emulsifying agent. They stabilize the system by forming a thin film around the globules of the dispersed phase.
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Advantages
1. They can mask the bitter taste and odor of drugs, thereby making them more palatable. e.g. castor oil, cod-liver oil etc.2. They can be used to prolong the release of the drug thereby providing sustained release action.
3. Essential nutrients like carbohydrates, fats and vitamins can all be emulsified and can be administered to bed ridden patients as sterile intravenous emulsions.
4. Emulsions provide protection to drugs which are susceptible to oxidation or hydrolysis.
5. Intravenous emulsions of contrast media have been developed to assist in diagnosis.
6. Emulsions are used widely to formulate externally used products like lotions, creams, liniments etc.
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Types Of Emulsions
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DIFFERENCE BETWEEN O/W AND W/O EMULSIONS
| | ||
| S.No | Oil in water emulsion (o/w) | Water in oil emulsion (w/o) |
| 1 | Water is the dispersion medium and oil is the dispersed phase | Oil is the dispersion medium and water is the dispersed phase |
| 2 | They are non greasy and easily removable from the skin surface | They are greasy and not water washable |
| 3 | They are used externally to provide cooling effect e.g. vanishing cream | They are used externally to prevent evaporation of moisture from the surface of skin e.g. Cold cream |
| 4 | Water soluble drugs are more quickly released from o/w emulsions | Oil soluble drugs are more quickly released from w/o emulsions |
| 5 | They are preferred for formulations meant for internal use as bitter taste of oils can be masked. | They are preferred for formulations meant for external use like creams. |
| 6 | O/W emulsions give a positive conductivity test as water is the external phase which is a good conductor of electricity. | W/O emulsions go not give a positive conductivity test as oil is the external phase which is a poor conductor of electricity. |
| 7 |  |  |
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Routes of administration of emulsions
Oral Emulsions: Generally o/w emulsions are used for internal use as the oil is more readily absorbed in a fine state of subdivision through the gastro intestinal tract and secondly the preparation becomes more palatable when water forms the continuous phase, as the medicinal oil is enveloped in a thin film of emulgent which masks the bitter and oily taste of the drug like liquid paraffin. Orally emulsions are also used to facilitate the absorption of the oil soluble drugs like vitamins A,D, E and K.
Example: Liquid Paraffin Oral Emulsion
Liquid Paraffin 500 ml
Methyl cellulose 20 20 g
Vanillin 0.5 g
Chloroform 2.5 ml
Benzoic acid solution 20 ml
Saccharin sodium 0.05 g
Purified Water q.s 1000ml
Uses: Laxative. It acts as an emollient purgative in chronic constipation especially during pregnancy and old age.
Example: Castor oil Emulsion
Castor oil 16 ml
Gum acacia q.s
Water 80 ml
Uses: Purgative
Example: Cod-Liver oil Emulsion
Cod-liver oil 30 ml
Syrup 12 ml
Ferric ammonium citrate 4 g
Cinnamon water q.s. 90 ml
Uses: Source of vitamin A and D. It is used as dietary supplement in infants and children to prevent the occurance of rickets and to improve nutrition in undernourished children and patients with rickets.
Rectal Emulsions: Enemas are formulated as o/w emulsions.
Topical Emulsions: For external use, emulsions may be either o/w or w/o type. Emulsions finds the maximum use in topical preparations , both for therapeutic and cosmetic use. Therapeutically they are used as carrier for a drug. In cosmetic industry o/w emulsions have been used for formulation of moisturing lotions, hand lotions and make up foundation lotions. When oily layers are desired to prevent moisture loss from the surface of skin, for barrier action and for cleansing action, then w/o emulsions are formulated like cold creams.
Example: Antiseptic cream
Cetrimide 1g
Cetostearyl alcohol 10 g
White soft paraffin 10 g
Liquid paraffin 29 g
Purified water 50 g
Uses: Antiseptic cream for the treatment of cuts, wounds and burns.
Example: Cold Cream
Liquid paraffin 20 g
Hard paraffin 4.5 g
Lanette wax 3.5 g
Glycerine 4.5 g
Water 17.5 g
Propyl paraben 0.1 g
Uses: Skin protective and skin smoothner.
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EMULSIFYING AGENTS
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Tests Used To Identify Emulsion Type
Since emulsion (o/w or w/o) looks the same in appearance with naked eyes, therefore certain tests have been developed to differentiate between them. At least two tests should be done to reach a conclusive decision about the identity of the emulsion.
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Dilution test
In this test the emulsion is diluted either with oil or water. If the emulsion is o/w type and it is diluted with water, it will remain stable as water is the dispersion medium but if it is diluted with oil, the emulsion will break as oil and water are not miscible with each other. Oil in water emulsion can easily be diluted with an aqueous solvent whereas water in oil emulsion can be diluted with a oily liquid.
Fig: Dilution Testfor oil in water emulsion
Fig: Dilution test for water in oil emulsion
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Conductivity Test
This test is based on the basic principle that water is a good conductor of electricity. Therefore in case of o/w emulsion , this test will be positive as water is the external phase. In this test. An assembly consisting of a pair of electrodes connected to a lamp is dipped into an emulsion. If the emulsion is o/w type, the lamp glows.
Fig: Conductivity test for oil in water emulsion
Fig: Conductivity test for water in oil emulsion
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Dye Solubility Test
In this test, when an emulsion is mixed with a water soluble dye such as amaranth and observed under the microscope, if the continuous phase appears red, then it means that the emulsion is o/w type as water is the external phase and the dye will dissolve in it to give color but if the scattered globules appear red and continuous phase colorless, then it is w/o type. Similarly if an oil soluble dye such as Scarlet red C or Sudan III is added to an emulsion and the continuous phase appears red, then it w/o emulsion.
Fig: Dye solubility test
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Cobalt Chloride Test
When a filter paper soaked in cobalt chloride solution is added to an emulsion and dried, it turns from blue to pink, indicating that the emulsion is o/w type.[edit]
Fluorescence Test
If an emulsion on exposure to ultra-violet radiations shows continuous florescence under microscope, then it is w/o type and if it shows only spotty fluorescence, then it is Oil in o/w type.[edit]
Instabilities In Emulsions
An emulsion is a thermodynamically unstable preparation so care has to be taken that the chemical as well as the physical stability of the preparation remains intact throughout the shelf life. There should be no appreciable change in the mean particle size or the size distribution of the droplets of the dispersed phase and secondly droplets of the dispersed phase should remain uniformly distributed throughout the system. Instabilities seen in emulsion can be grouped as[edit]
Creaming
An emulsion is said to cream when the oil or fat rises to the surface, but remains in the form of globules, which may be redistributed throughout the dispersion medium by shaking. An oil of low viscosity tends to cream more readily than one of high viscosity. Increasing the viscosity of the medium decreases the tendency to cream. Creaming is a reversible phenomenon which can be corrected by mild shaking. The factors affecting creaming are best described by stroke’s lawV= 2r2 (d1-d2) g/9η
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
The following approaches can be used for decreasing Creaming
Reduction of globule size: According to stroke’s law, rate of creaming is directly proportional to the size of globules. Bigger is the size of the globules, more will be the creaming. Therefore in order to minimize creaming, globule size should be reduced by homogenization.
Increasing the viscosity of the continuous phase: Rate of creaming is inversely proportional to the viscosity of the continuous phase i.e. more the viscosity of the continuous phase, less will the problem of creaming. Therefore to avoid creaming in emulsions, the viscosity of the continuous phase should be increased by adding suitable viscosity enhancers like gum acacia, tragacanth etc.
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Cracking
Occasionally, it happens that an emulsion cracks during preparation, i.e., the primary emulsion does not become white but acquires an oily translucent appearance. In such a case, it is impossible to dilute the emulsion nucleus with water and the oil separates out. Cracking of emulsion can be due to addition of an incompatible emulsifying agent, chemical or microbial decomposition of emulsifying agent, addition of electrolytes, exposure to increased or reduced temperature or change in pH.[edit]
Phase Inversion
In phase inversion o/w type emulsion changes into w/o type and vice versa. It is a physical instability. It may be brought about by the addition of an electrolyte or by changing the phase volume ratio or by temperature changes. Phase inversion can be minimized by using the proper emulsifying agent in adequate concentration, keeping the concentration of dispersed phase between 30 to 60 % and by storing the emulsion in a cool place.[edit]
Points to be considered during formulations of emulsions
Stability of the active ingredient
Stability of the excipients
Visual appearance
Color
Odor (development of pungent odor/loss of fragrance)
Viscosity, extrudability
Loss of water and other volatile vehicle components
Concentration of emulsifier
Order of addition of ingredients
Particle size distribution of dispersed phases
pH
Temperature of emulsification
Type of equipment
Method and rate of cooling
Texture, feel upon application (stiffness, grittiness, greasiness, tackiness, spreadibility)
Microbial contamination/sterility (in the unopened container and under conditions of use)
Release/bioavailability (percutaneous absorption)
Phase distribution, Phase Inversion (homogeneity/phase separation, bleeding
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Packaging, Labelling And Storage Of Emulsions
Depending on the use, emulsions should be packed in suitable containers. Emulsions meant for oral use are usually packed in well filled bottles having an air tight closure. Light sensitive products are packed in amber coloured bottles. For viscous emulsions, wide mouth bottles should be used. The label on the emulsion should mention that these products have to be shaken thoroughly before use. External use products should clearly mention on their label that they are meant for external use only. Emulsions should be stored in a cool place but refrigeration should be avoided as this low temperature can adversely effect the stability of preparation.[edit]
Preservation Of Emulsions
Preservation from microorganisms:It is necessary to preserve the emulsions from microorganisms as these can proliferate easily in emulsified systems with high water content, particularly if carbohydrates, proteins or steroidal materials are also present.
Contamination due to microorganisms can result in problems such as color and odor change, gas production, hydrolysis, pH change and eventually breaking of emulsion. Therefore is necessary that emulsified systems be adequately preserved. An ideal preservative should be nonirritant, nonsensitizing and nontoxic in the concentration used. It should be physically as well as chemically compatible with other ingredients of the emulsions and with the proposed container of the product. It should not impart any taste, color or odor to the product. It should be stable and effective over a wide range of pH and temperature. It should have have a wide spectrum of activity against a range of bacteria, yeasts and moulds. The selective preservative should have high water solubility and a low oil/water partition coefficient. It should have bactericidal rather than bacteriostatic activity.
Examples of antimicrobial preservatives used to preserve emulsified systems include parahydroxybenzoate esters such as methyl, propyl and butyl parabens, organic acids such as ascorbic acid and benzoic acid, organic mercurials such as phenylmercuric acetate and phenylmercuric nitrate, quarternary ammonium compounds such as cetrimide, cresol derivatives such as chlorocresol and miscellaneous agents such as sodium benzoate, chloroform and phenoxyethanol.
Preservation from oxidation:
Oxidative changes such as rancidity and spoilage due to atmospheric oxygen and effects of enzymes produced by micro-organisms is seen in many emulsions containing vegetables and mineral oils and animal fats. Antioxidants can be used to prevent the changes occurring due to atmospheric oxygen.
Antioxidants are agents having a high affinity for oxygen and compete for it with labile substances in the formulation. The ideal antioxidant should be nontoxic, nonirritant, effective at low concentration under the expected conditions of storage and use, soluble in the medium and stable. Antioxidants for use in oral preparation should also be odorless and tasteless.
Some of the commonly used antixidants for emulsified systems include alkyl gallate such as ethyl, propyl or dodecyl gallate, butylated sshydroxyanisole (BHT), butylated hydroxytoluene (BHT)
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Preparation Of Emulsions
See Main article Methods for preparing emulsions[edit]
Properties of emulsion
See Main article Properties of emulsionPROPERTIES OF EMULSIONS The basic properties which should be present in an emulsion include appearance, feel, odour, desirable viscosity, consistency, effectiveness and stability. These properties depends on the ingredients, type of emulsion, ratio of the two phases, type and quantity of emulsifying agents and method of emulsification . O/w emulsions will generally have a sheen or matte surface as compared to w/o emulsions which have a shiny or oily surface due to the presence of oil as external phase. W/o emulsions are oily and greasy in nature, not easily removable from the surface of the skin whereas o/w emulsions are non greasy and easily removable from the skin surface. The viscosity of the emulsions depends generally on the viscosity of the continuous phase. As the ratio of dispersed phase increases, the viscosity also increases to a point where emulsion starts loosing its fluidity.
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Quality control tests for Emulsions
The following are the quality control tests done for emulsions:1. Determination of particle size and particle count: Determination of changes in the average particle size or the size distribution of droplets is an important parameter used for the evaluation of emulsions. It is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter counter apparatus.
2. Determination of viscosity: Determination of viscosity is done to assess the changes that might take place during aging. Emulsions exhibit non-newtonian type of flow characterstics. The viscometers which should be used include cone and plate viscometers. Capillary and falling sphere type of viscometrs should be avoided. For viscous emulsions, the use of penetrometer is recommended as it helps in the determination of viscosity with age. In case of o/w emulsions, flocculation of globules causes an immediate increase in viscosity. After this change, the consistency of the emulsion changes with time. In case of w/o emulsions, , the dispersed phase particles flocculate quite rapidly resulting in a decrease in viscosity, which stabilizes after 5 to 15 days. As a rule, a decrease in viscosity with age reflects an increase of particle size due to coalescence.
3. Determination of phase separation: This is another parameter used for assessing the stability of the formulation. Phase separation may be observed visually or by measuring the volume of the separated phases.
4. Determination of electrophoretic properties: Determination of electrophoretic properties like zeta potential is useful for assessing flocculation since electrical charges on particles influence the rate of flocculation. O/W emulsion having a fine particle size will exhibit low resistance but if the particle size increase, then it indicates a sign of oil droplet aggregation and instability.
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Stability testing
Stability of emulsions is an important parameter for the formulator. Stability testing of emulsions involves determining stability at long term storage conditions, accelerated storage conditions, freezing and thawing conditions. Stress conditions are applied in order to speed up the stability testing. The stress conditions used for speeding up instability of emulsions include:
Centrifugal force Agitational force Aging and temperature The following physical parameters are evaluated to assess the effect of any of the above stress conditions:
· Phase separation
· Viscosity
· Electrophoretic properties
· Particle size and particle count
Particle size and size distribution The freeze-thaw cycling technique used to assess emulsions for stress testing for stability testing result in increase of particle growth and may indicate future state after long storage. It is of importance to study the changes for absolute particle size and particle size distribution. It is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter counter apparatus. None of these methods are direct methods. However microscopic method allows the observer to view the actual particles.
Rheological studies Cone and Plate viscometer with variable shear stress control can be used for evaluating viscosity of emulsions.
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Emulsion Products
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