PHM 3110 Lecture 10 - Emulsions PDF

EMULSIONS Ms. Colette Gouveia Lecture 10 Suspension Emulsion is a two phased is a dispersion in system in which a which the dispersed finely divided solid is phase is composed dispersed in a of small globules of a continuous phase of liquid...

EMULSIONS Ms. Colette Gouveia Lecture 10 Suspension Emulsion is a two phased is a dispersion in system in which a which the dispersed finely divided solid is phase is composed dispersed in a of small globules of a continuous phase of liquid distributed solid, liquid, or gas. throughout a vehicle in which it is  Emulsions An emulsion is a thermodynamically unstable system consisting of at least two immiscible liquid phases one of which is dispersed as globules in the other liquid phase stabilized by a third substance called emulsifying agent. Or An emulsion is a dispersion in which the dispersed phase is composed of small globule of a liquid is distributed throughout a vehicle in which it is immiscible.  Emulsions An emulsion is a biphasic liquid preparation containing two immiscible liquids, one of which is dispersed as minute globules into the other. The liquid which is converted into minute globules is called the ‘dispersed phase’ and the liquid in which the globules are dispersed is called the ‘continuous phase’. Normally, two immiscible liquids cannot be dispersed for a long period. So, an emulsifying agent is added to the system. - It forms a film around the globules to scatter them indefinitely in the continuous phase, so that a stable emulsion is formed. The globule size in emulsion varies from 0.25 to 25 µm.  Types of Emulsions 1. Oil in water emulsions 2. Water in oil emulsions 3. Multiple emulsions (O/W/O) or (W/O/W) 4. Microemulsions.  Internal Phase or External Phase in Emulsions Generally, the two liquids that form an emulsion are oil and water. The dispersed liquid is known as the Internal or Discontinuous phase. whereas The dispersion medium is known as the External or Continuous phase Two types of emulsion 1.Oil in water emulsion (O/W emulsion): oil is in the dispersed phase and water in dispersion medium or continuous phase. 2.Water in oil emulsion (W/O emulsion): water is in the dispersed phase and oil in dispersion medium or continuous phase.  Based on Dispersed Phase Oil in Water (O/W): Oil droplets dispersed in water W/O): Water in Oil (Water droplets dispersed in oil Size of Liquid droplets 0.01 – 0.2 mm Micro emulsions (Thermodynamically Stable) 0.2 – 50 mm Macro emulsions (Kinetically Stable)  Difference between O/W and W/O Emulsions (o/w) (w/o Water is the dispersion Oil is the dispersion medium, and oil is the medium, and water is the dispersed phase. dispersed phase. non greasy and easily greasy and not water removable from the skin. washable. used externally to provide used externally to prevent cooling effect e.g. vanishing evaporation of moisture cream. from the surface of skin e.g. Cold cream. preferred for internal use as bitter taste of oils can be preferred for external use masked. like creams.)  Types of Emulsions Multiple Emulsions Multiple emulsions are the emulsion system in which the dispersed phase contain smaller droplets that have the same composition as the external phase. The multiple emulsions are also considered to be of two types: - Oil-in-Water-in-Oil (O/W/O) emulsion system - Water-in-Oil-In-Water (W/O/W) emulsion system Oil-in-Water-in-Oil: In O/W/O systems ,an aqueous phase (hydrophilic) separates internal and external oil phase. In other words, O/W/O is a system in which water droplets may be surrounded in oil phase, which actually encloses one or more oil droplets. Water-in-Oil-In-Water: In W/O/W systems, an organic phase (hydrophobic) separates internal and external aqueous phases. In other words, W/O/W is a system in which oil droplets may be surrounded by an aqueous phase, which in turn encloses one or several water droplets. These systems are the most studied among the multiple emulsions.  TYPES OF EMULSIONS MICROEMULSIONS: Unlike the common macro emulsion ,it appears as a clear and transparent liquid mixtures of oil, water and surfactant, frequently in combination with a co-surfactant. Diameter of internal phase droplets ranged between 10- 200nm. Thermodynamically stable. In contrast to ordinary emulsion, microemulsions form upon simple mixing of the components and do not require the high shear conditions generally used in the formation of ordinary emulsions. The two basic types of Microemulsions are (o/w) and (w/o).  EMULSIONS Emulsion is stabilized by an emulsifying agent. Globule diameter 0.1- 100µm e.g. milk, ice cream, paints, lotions of low viscosity to ointments and creams which are semi-solids. Classification: 1. Basing on dispersed phase – i.e o/w and w/o :Medicinal emulsions are mostly o/w type. 2. Basing on globule size – i.e Microemulsions (0.01µm) Fine emulsions (0.25-25 µm) Emulsifying Agents  Emulsifying Agents Emulsifying agents are substances that are soluble in both water and fat and enable fat to be uniformly dispersed in water as an emulsion. It is any compound that lowers the interfacial tension and forms a film at the interface The emulsifying agents reduce the interfacial tension between two phases i.e., oily phase and aqueous phase and thus make them miscible with each other to form a stable emulsion. Emulsifying agents are also known as emulgents or emulsifiers. E.g. Acacia, Glyceryl monostearate, Tragacanth, etc.  Classification of Emulsifying Agents 1. Natural Emulsifying Agents Animal origin-wool fat. Egg yolk, gelatin, cholesterol, pectin, chondrus. Plant origin- Acacia, Tracaganth. 2. Synthetic Emulsifying Agents Anionic-sodium stearate, sodium lauryl sulphate Cationic- Benzalkonium chloride Non-ionic- Sorbitan Fatty acid esters (Spans), Polyoxyethylene sorbitan fatty acid esters (Tweens) 3. High molecular weight alcohols- Stearyl alcohol, cetyl alcohol & glyceryl monostearate. 4. Finely divided solids- Bentonite, magnesium hydroxide & aluminum hydroxide.  Mechanism of action of emulsifying agents When one liquid film is broken into large number of small globules then interfacial area increases Interfacial energy associated with interface also increases To reduce interfacial energy, globules of dispersed phase tends to coalesce (merge) To prevent coalescence and to keep system stable in disperse state it is necessary to add an emulsifying agent  Mechanism of action of emulsifying agents As a result, a few processes occur: 1. Reduction of interfacial tension - Thermodynamic stabilization 2. Formation of interfacial film barrier (stearic stabilization) - Mechanical barrier to coalescence 3. Formation of electric double layer- Electrical barrier to approach of globules Thermodynamic stabilization of emulsion Interfacial free energy (ΔG) in emulsion ΔG =γLL ΔA γLL is interfacial tension Approaches for stable emulsion is to reduce γLL by adding surface active agent also known as a surfactant.  Mechanisms of emulsion formation Emulsifying agent prevent coalescence of globules of disperse by forming film around globules. An emulsifying agent is any material that enhances the stability of an emulsion. Emulsifying agents can be divided into 3 groups 1. Monomolecular adsorption film(Surfactants)- Spans, Tweens. 2. Multimolecular adsorption film (colloids) – Acacia, Gelatin. 3. Solid particle Adsorption (Finely divided solids)- Bentonite, Veegum.  Monomolecular Adsorption Film Surfactants form monomolecular film at oil-water interface and cover the globule. The film should be strong, elastic, flexible to reform when broken. Emulsion stability depends on physical, chemical, mechanical properties of film. Oil soluble and water-soluble surfactant combination interactions forms strong film. Ionic surfactants develop repulsive forces between globules to prevent coalescence. Nonionic surfactants forms thick film on globule to prevent coalescence Combination of surfactants is generally used as it is more effective  Synthetic Emulsifiers ANIONIC AGENTS – include sulfuric acid esters, sulfonic acid derivatives, and soaps - Alkali soaps – form O/W emulsion - Metallic soaps – form W/O emulsion - Monovalent and Polyvalent soaps – form W/O emulsion CATIONIC AGENTS - Used as surfactant in 1% concentration Example: Benzalkonium chloride NONIONIC EMULSIFIERS - Resistant to the addition of acids and electrolytes Examples: - Sorbitan esters – SPANS, hydrophobic, low HLB values, form W/O emulsions - Polysorbates – TWEENS, hydrophilic, high HLB values, form O/W emulsions HLB SYSTEM - Hydrophile – Lipophile Balance Used to classify non-ionic surfactants All NON –IONIC surfactants have an HLB value. - The higher the HLB number, the more hydrophilic - The lower the HLB number, the more lipophilic. HYDROPHILIC SURFACTANTS - High HLB values (>10) - Form O/W emulsion LIPOPHILIC SURFACTANTS - Low HLB values (1-10) - Form W/O emulsion  Application of Surfactants HLB VALUE SURFACTANT RANGE APPLICATION  1–3 Antifoaming agents  4–6 Water-in-Oil emulsifiers  7–9 Wetting agents  8 – 18 Oil-in-Water emulsifiers  13 – 15 Detergents  10 – 18 Solubilizing agents  Monomolecular Adsorption (HLB) Type of emulsion produced, depend on property of emulsifying agents... Hydrophilic lipophilic balance (HLB) Type of emulsion is function of relative solubility of the surfactant Brancroft’s Rule: States that though emulsifying agent has affinity towards polar and non-polar liquids, they have preferential solubility in one of the liquid which becomes continuous phase. Ionic type of emulsifying agent not preferred for internal use as they interact with bio membranes and affect cell functioning. Natural emulsifying agent show batch-batch variation and microbial growth. High HLB Surfactant prefer formation o/w emulsion and vice versa Surfactants: - HLB (3-8) - W/O emulsifying agent- Spans - HLB (8-16) - O/W emulsifying agent- Tweens.  Multimolecular Adsorption Hydrophilic colloids (mucilage of gum acacia) are different in action from surfactants They do not cause lowering of interfacial tension They exert their action by forming multimolecular layers at o/w interface. They increase viscosity of dispersion medium  Emulsifying agents (Hydrocolloids Examples) 1. Natural Polysaccharides: The main problem with these agents is their natural variability between batches and microbial contamination. These materials should not be used externally as they leave a sticky feel on the skin. Acacia is the best emulsifying agent for extemporaneously prepared oral emulsions as it forms a thick film at the oil- water interface to act as a barrier to coalescence. It is too sticky for external use. Tragacanth is used to increase the viscosity of an emulsion and prevent creaming. Other polysaccharides, such as starch and pectin are used to stabilize an emulsion. 2. Semi-synthetic polysaccharides: These are derived from the naturally occurring polysaccharide cellulose and generally form o/w emulsions. Examples include low-viscosity grades of Methylcellulose (MC),Carboxymethylcellulose (CMC) and Hydroxypropyl methylcellulose (HPMC) 3. Synthetic hydrocolloids: Carbopol ,Polyvinyl alcohol (PVA) and Polyvinyl pyrolidone (PVP)  Solid Particles Adsorption Solid particles that can be wetted by oil as well as water can act as the emulsifying agent Their concentration is higher at interface hence finely divided solid particles adsorb at oil-water interface to form rigid film. They form a particulate layer around dispersed particles. These agents swell in the dispersion medium to increase viscosity and reduce the interaction between dispersed droplets i.e the film acts as mechanical barrier to prevent coalescence. Example of agents: w/o) - ( Bentonite (Al2O3.4SiO2.H2O), o/w ) - (Veegum (Magnesium Aluminum Silicate) The stability of emulsion depends on the finer state of sub- division of solid particles, irregular surface & charge on surface of the particle. Theories of Emulsification  Theories of Emulsification Many theories have been advanced to account for the way or means by which the emulsion is stabilized by the emulsifier. There is no universal theory of emulsification, because emulsions can be prepared using several different types of emulsifying agents, each of which depends on a different principle for its action to achieve a stable product. For a theory to be meaningful, it should be capable of explaining : (1) the stability of the product (2) the type of emulsion formed THEORIES 1) Electric Double Layer Theory. 2) Phase Volume Theory. 3) Hydration Theory of Emulsions 4) Oriented wedge theory. 5) Adsorbed Film and Interfacial tension Theory  Electric Double Layer Theory The oil globules in a pure oil and pure water emulsion carry a negative charge. The water ionizes so that both hydrogen and hydroxyl ions are present. The negative charge on the oil globule are as a result of adsorption of the OH ions. These adsorbed hydroxyl ions form a layer around the oil globules. A second layer of oppositely charged ions forms a layer in the liquid outside the layer of negative ions. The electric charge is a factor in all emulsions, even those stabilized with emulsifying agents.  Phase Volume Theory If spheres (globules) of the same diameter are packed as closely as possible, it is possible that one sphere can touch 12 others and the volume the spheres occupy is about 74 per cent of the total volume. Thus, if the spheres or drops of the dispersed phase remain rigid it is possible to disperse 74 parts of the dispersed phase in the continuous phase; but if the dispersed phase is increased to more than 74 parts of the total volume, a reversal of the emulsion will occur. However, the dispersed phase does not remain rigid in shape but the drops flatten out where they come in contact with each other, nor are all the dispersed particles the same so that it is possible for the dispersed phase to consist of from 1 to 99 per cent of the  Hydration Theory of Emulsions Hydration Theory of Emulsions: Fischer and Hooker state that hydrated colloids make the best emulsifiers. Fischer states the emulsifying agent, by which a permanent emulsion is obtained, "proves to be a hydrophilic colloid when water and oil emulsions are concerned Fischer and Hooker have found albumin, casein, and gelatin to be good emulsifying agents.  Oriented wedge theory This theory deals with formation of monomolecular layers of emulsifying agent curved around a droplet of the internal phase of the emulsion. Example: In a system containing two immiscible liquids, emulsifying agent would be preferentially soluble in one of the phases and would be embedded in that phase. Hence an emulsifying agent having a greater hydrophilic character will promote o/w emulsion and vice-versa. Sodium oleate is dispersed in water and not oil. It forms a film which is wetted by water than by oil. This leads the film to curve so that it encloses globules of oil in water. Adsorbed film and interfacial tension theory Lowering interfacial tension is one way to decrease the free surface energy associated with the formation of droplets. Assuming the droplets are spherical, ΔF= 6 γV D V= volume of the dispersed phase in ml, d is the mean diameter of the particles. γ = interfacial tension It is desirable that: - The surface tension should be reduced below 10 dynes/cm by the emulsifier and it should be absorbed quickly.  RHEOLOGICAL PROPERTIES OF EMULSIONS 1.The following flow related attributes are desirable for the overall performance of an emulsion Removal of an emulsion from a bottle or tube Flow of an emulsion through a hypodermic needle Spreadability of an emulsion on the skin Stress induced flow changes during manufacture 2. The rheology of emulsions has many similar features to that of suspensions. However, they differ in three main aspects The liquid/liquid interface that contains surfactant or polymer layers introduces a response to deformation and one has to consider the interfacial rheology The dispersed phase viscosity relative to that of the medium has an effect on the rheology of the emulsion The deformable nature of the dispersed phase droplets, particularly for large droplets, has an effect on the emulsion rheology  RHEOLOGICAL PROPERTIES OF EMULSIONS Phase- Type of flow Viscosity In general, dilute emulsions volume measurem exhibit “Newtonian flow”. ratio ent As the viscosity of the emulsion Dilute Newtonian Single increases, flocculation of emulsion point globules will be reduced - 5% viscomet because the mobility of globules er is restricted, leads to creaming. Conc. Pseudoplast Multiple Due to this antagonistic effect, an optimum viscosity is emulsion ic point desirable for good stability. - 50% viscomet Concentrated emulsions exhibit Conc. Plastic er “non-Newtonian flow” and emulsion - Cone & multipoint viscometers are used – 74 % plate for viscosity analysis.  Advantages of emulsions 1. Mask the unpleasant taste: Unpleasant tasted drug due to globules in emulsion Ex: laxatives, vitamin-A 2. Economical: Expensive solvents are used to dissolve lipids. In emulsion lipids are dispersed in water (cheaper). 3. Improved bioavailability: Absorption of drugs is faster & better in emulsion Ex: griseofulvin corn oil-water emulsion > griseofulvin tablets 4. Sustained release medication: - Water soluble antigen dispersed in oil i.e o/w emulsion - Injected in body e.g Deposit in muscle which results slow drug release - Multiple emulsions (o/w/o) (w/o/w) give sustained release 5. Nutritional supplement: Terminally ill patients are given nutrition parenterally. Emulsion where the oil phase (fats) and the aqueous. phase (nutrients) 6. Diagnostic purpose: radio-opaque emulsions are used in X-ray examinations 7. Topical use: Concentrated emulsion i.e semi-solids. E.g. cold cream, vanishing cream, benzyl benzoate etc., Stability of Emulsions  Stability An emulsion is said to be stable if it remains as such after its preparation, i.e., the dispersed globules are uniformly distributed through out the dispersion medium during its storage. Emulsion should be chemically stable and there should not be any bacterial growth during its shelf life. Stability problems may occur during the storage of an emulsion:- 1.Flocculation 2.Sedimentation and creaming 3.Thermodynamic instability (coalescence or cracking) 4. Phase inversion  Stability of Emulsions Flocculation : Re dispersible association of particle within an emulsion to form large aggregates. Precursor to the irreversible coalescence. Differs from coalescence mainly in that interfacial film and individual droplets remain intact. Influenced by the charges on the surface of the emulsified globules.  Stability of Emulsions Creaming and sedimentation: As the dispersed droplets are subjected to gravity force, they tend to move upward (creaming) or downward (sedimentation) but not both. Creaming usually happens in o/w emulsions. Sedimentation usually happens in w/o emulsion. The rate of sedimentation or creaming is described by Stoke’s law. Where v= velocity of sedimentation or creaming of a dispersed particle of radius r, and density σ, in a liquid of density ρ, and viscosity ŋ, and where g is the acceleration due to gravity.  Stability of Emulsions Creaming and sedimentation: The process is reversible, and gentle shaking redistributes the droplets throughout the continuous phase. However, creaming is undesirable because - It is inelegant and inaccurate dosing is possible if shaking is not thorough. - Additionally, creaming increases the likelihood of coalescence of globules and therefore break down of the emulsion due to cracking.  Stability of emulsions Cracking or coalescence: Emulsions are thermodynamically unstable systems; there is interfacial free energy (IFE) between the two phases. To enhance their stability, the dispersed droplets come closer to each other and fuse in an attempt to decrease the exposed surface area. Coalescence is the fusion of two or more droplets of the disperse phase forming one droplet. This ends up to the separation of the disperse phase as a separate layer (phase separation). Coalescence is an irreversible process and redispersion cannot be achieved by shaking.  Stability of emulsions How to enhance stability (to prevent creaming and cracking)? Globule size: - Smaller particles have slower creaming or sedimentation than larger particles (Stoke’s law). Stable emulsions require a maximal number of small sized (1-3 µm) globules and as few as possible larger (>15 µm) diameter globules. A homogenizer will efficiently reduce droplet size by forcing the emulsion through a small aperture to reduce the size of the globules. - Additionally, reducing droplet size may additionally increase the viscosity if more than 30% of disperse phase is present.  Stability of emulsions How to enhance stability ( to prevent creaming and cracking)? Viscosity of the continuous phase: - Increasing the viscosity of the continuous phase will reduce the potential for globule creaming and hence coalescence as this reduces the movement of globules. - How to increase viscosity? Viscosity enhancing agents, which increase the viscosity of the continuous phase, may be used in o/w emulsions. e.g tragacanth, sodium alginate and methylcellulose. Higher percentages of oil phase (o/w). Decreasing the globule size of the internal phase. Higher amounts of solid fats in the oily phase (i.e. high ratios of solid fat to liquid fats).  Stability of emulsions How to enhance stability ( to prevent creaming and cracking)? Using emulsifying agents (hydrocolloids, surfactants and other) : - Forming interfacial film mechanical barrier which decreases the potential for coalescence (more important). - Surfactants may reduce the interfacial tension between the two phases (less important). - Hydrocolloids enhance the viscosity of the medium. Note: Care should be taken for any effects that could affect the interfacial film (chemical, physical or biological effects).  Stability of emulsions How to enhance stability ( to prevent creaming and cracking)? Storage temperature: - Extremes of temperature can lead to an emulsion cracking. - When water freezes it expands, so undue pressure is exerted on dispersed globules and the emulsifying agent film, which may lead to cracking. - Conversely, an increased temperature decreases the viscosity of the continuous phase and disrupts the integrity of the interfacial film around the globules. An increasing number of collisions between droplets will also occur, leading to increased creaming and cracking.  Stability of emulsions Phase inversion Emulsion type is determined by: - The oil to water ratio (amounts). - The solubility of the emulsifying agent. Phase inversion is the process in which an emulsion changes from one type to another, say o/w to w/o. The most stable range of disperse phase concentration is 30- 60%. If the amount of disperse phase approaches or exceeds a theoretical maximum of 74% of the total volume, then phase inversion may occur. Addition of substances which alter the solubility of an emulsifying agent may also cause phase inversion. The process is irreversible. Methods for evaluation of stability of emulsion Size frequency analysis over the time by microscopic observation Velocity of creaming (as it is proportional to droplet diameter) Globule size analysis using coulter-counting, ultra centrifugal Turbidimetric analysis Manufacture of Emulsions  Manufacture of Emulsions Emulsions can be prepared via extemporaneous production, which is more concerned with small scale methods. OR Commercially, where emulsions are prepared in large volume mixing tanks and refined and stabilized by passage through a colloid mill or homogenizer. Each method requires that energy be put into the system in some form. The energy is supplied in a variety of ways: trituration, homogenization, agitation, and heat.  Extemporaneous Methods Emulsification process can be carried out by four methods mainly : 1. DRY GUM METHOD (Continental method) 4:2:1 ratio of oil: water: gum Formation of Primary Mucilage as the nucleus of the emulsion 2. WET GUM METHOD (English method) 4:2:1 of oil : water : gum Formation of Primary Gum as the nucleus of the emulsion. 3. FORBES BOTTLE METHOD – 2:2:1 ratio of oils : water : gum Applicable to emulsions containing volatile oils. 4. AUXILLIARY METHOD Hand homogenizer, which forces the emulsion through a very small orifice, reducing the dispersed droplet size to about 5 microns or less.  DRY GUM Method Dry gum method is used to prepare the initial or primary emulsion from oil, water, and a hydrocolloid or "gum" type emulsifier. Dry Gum Methodology (4 parts oil, 2 parts water, and 1 part Emulsifier). Procedure: 1. In a mortar, 1 part gum is levigated with the 4 parts oil until the powder is thoroughly wetted; then the 2 parts water are added all at once, and the mixture is vigorously triturated until the primary emulsion formed is creamy white and produces a "clicking" sound as it is triturated. 2. Active ingredients, preservatives, color, flavors are added as a solution to the primary emulsion. 3. When all agents have been incorporated, the emulsion should be transferred to a calibrated vessel, brought to final volume with water.  Wet Gum Method Wet Gum Methodology (Oil 4 parts + Water 2 parts + Emulsifier 1 parts) Procedure: 1.In this method, the proportions of oil, water, and emulsifier are the same (4:2:1), but the order and techniques of mixing are different. 2.The 1 part gum is triturated with 2 parts water to form a mucilage; then the 4 parts oil is added slowly, in portions, while triturating. 3. After all the oil is added, the mixture is triturated for several minutes to form the primary emulsion. 4.Then other ingredients may be added as in the continental method.  Forbes Bottle Method Procedure: 1. This method may be used to prepare emulsions of volatile oils and oleaginous substances of very low viscosities. 2. This method is a variation of the dry gum method. 3. One part powdered acacia (or other gum) is placed in a dry bottle and four parts oil are added. 4. The bottle is capped and thoroughly shaken. 5. To this, the required volume of water is added all at once, and the mixture is shaken thoroughly until the primary emulsion forms.  Large Scale Methods Physical parameters affecting the droplet size distribution, viscosity, and stability of emulsion: Location of the emulsifier, method of incorporation of the phases, the rates of addition , the temperature of each phase and the rate of cooling after mixing of the phases considerably Energy may be supplied in the form of: Heat Homogenization Agitation Mechanical equipment for Emulsification Mechanical An emulsion may be stirred Stirrers by means of various impellers mounted on shafts, which are placed directly into the system to be emulsified. This is used for mixing, suspending, milling, dispersing, disintegrating solids etc. It reduces batch time. It consists of stator and rotor assembly. The rotor rotates inside the stator assembly which is fixed with three tie rods to the motor.  Propeller Mixers Simple top entering propeller mixers are adequate for routine development work in the laboratory and production. The degree of agitation is controlled by propeller rotation, but the pattern of liquid flow and resultant efficiency of mixing are controlled by the type of impeller, its position in the container, the presence of baffles, and the general shape of the container. These stirrers can not be used when : vigorous agitation is needed; extremely small droplets are needed. Foaming at high shear rates must be avoided. These mixers may have paddle blades, counter rotating blades or planetary blades. Major types Turbine Type Mixers If more vigorous agitation is required or viscosity is more , turbine type mixers can be used Homogenization  Homogenization Homogenization is the process of emulsifying two immiscible liquids (i.e. liquids that are not soluble in one another) or uniformly spreading solid particles throughout a liquid. Homogenization is a unit operation using a processing equipment known as homogenizers which are oriented at lowering the size of droplets in liquid-liquid or solid liquid dispersions. In homogenizers the dispersion of two liquids is achieved by forcing their mixture through a small inlet orifice at big pressures. Homogenizers can be made with more than one emulsifying stage, and it is possible to recycle the emulsion through the homogenizer more than one time. Homogenizers raise the temperature of the emulsions; hence cooling may be required. It can be used when a reasonably mono disperse emulsion of small droplet size ( 1nm) is required. The benefits include increased product stability, homogeneity, consistency, viscosity, shelf life, improved flavour and colour. The rate of cell rupture is proportional to approximately the third power of the turbulent velocity of the product flowing through the homogenizer channel, which in turn is directly proportional to the applied pressure. Thus, the higher the pressure, the higher the efficiency of disruption each run through the machine. The operational parameters which impact the efficiency of high- pressure homogenizers are as follows: Pressure Temperature Number of passes Valve and impingement design Flow rate  Colloid Mills They operate on principle of high shear which is normally generated between rotor and stator of the mill. Colloid mill consists of a fixed stator plate and a high-speed rotating rotator plate. Material drawn or pumped through an adjustable gap set between the rotor and stator is homogenized by the physical action and the centrifugal force is created by high rotation of the rotor which operates within 0.005 to 0.010 inch of the stator.  Ultrasonifiers Ultrasonic energy s used to produce pharmaceutical emulsions. These transduced piezoelectric devices have limited output and are expensive. They are useful for laboratory preparation of emulsions of moderate viscosity and extremely low particle size. Commercial equipment is based on principle of Pohlman liquid whistle. The dispersion is forced through an orifice at modest pressure and is allowed to impinge on a blade. The pressure range is from 150-350 psi. This pressure causes blades to vibrate rapidly to produce an ultrasonic note. When the system reaches a steady state, a cavitational field is generated at the leading edge of the blade and the pressure fluctuations of approximately. 60 tones psi can be achieved in commercial equipment. Tests for Emulsions Type The followings tests are done to distinguish between o/w and w/o emulsions. Pharmaceutical Applications  Pharmaceutical Applications Emulsions can be used for following dosage forms 1. Oil Products : Emulsions are used for administering drugs orally due to following reasons : a) More palatable : Objectionable taste or texture of medicinal agents become masked. b) Better absorption : Due to small globule size, the medicinal agent is quickly absorbed. O/W Parenteral : a) I/V route: nutrients are emulsified and given to patients by i/v route. Such emulsions have particle size less than 100 nm. b) Depot injections :W/o emulsions are used to disperse water soluble antigenic materials in mineral oil for i/m depot injection Topical Products : a) O/W emulsions are more acceptable as water washable drug bases for cosmetic purposes b) W/O emulsions are used for treatment of dry skin. Emulsions have following advantages when used for topical purpose: a. Patient acceptance b. washable character, c. Acceptable viscosity, d. Less greasiness.