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Patel College of Pharmacy, KapadwanjINTRODUCTION : INTRODUCTION Definition: “A solution is a liquid-preparation that contains one or more soluble chemical substances dissolved in a specified solvent.” Liquid dosage form mainly divided into Solution 2. Syrup 3. Suspension 4. EmulsionAdvantages : Advantages Immediately available for absorption. Administration convenient, particularly for infants, psychotic patients. Easy to color, flavor & sweeten. Liquids are easier to swallow than solids and are therefore particularly acceptable for pediatric patient. A solution is an homogeneous system and therefore the drug will be uniformly distributed throughout the preparation. Some drugs like aspirin, KCl can irritate gastric mucosa if used orally as a solid dosage forms. But this effect can be reduce by solution system.PowerPoint Presentation: Disadvantages Bulky than tablets or capsule, so difficult to carry transport. Less stable in aqueous system. Incompatibility is faster in solution than solid dosage form. Patients have no accurate measuring device. Accident breakage of container results in complete loss. Solution often provide suitable media for the growth of micro organisms. The taste of a drug, which is often unpleasant, is always more pronounced when in solution than in a solid form.ADDITIVES USED IN LIQUID DOSAGE FORMS: ADDITIVES USED IN LIQUID DOSAGE FORMS Vehicles Buffers Density modifiers Stabilizer Isotonicity modifiers Viscosity enhancement Preservatives Sweetening agents Reducing agents and antioxidants Flavors and perfumes ColorsPowerPoint Presentation: VEHICLES: Two types of vehicles; a. Aqueous vehicles b. Non- aqueous vehicles.a. Aqueous vehicles: a. Aqueous vehicles Water is the solvent most widely used as a vehicle for pharmaceutical products because of its physiological compatibility and lack of toxicity. It possesses a high dielectric constant, which is essential for ensuring the dissolution of a wide range of ionizable materials.PowerPoint Presentation: Types of pharmaceutical water. Sr . No. Name Properties Remarks 1 Water -Cheap -High Dielectric Constant -Miscible with alcohol, glycerol and other polar solvents -Non flammable -Inert -Impurities 2. Purified Water -Prepared by Distillation or ion exchange resin -used for Parenterals Preparation 3. Water for injection -Sterile -Pyrogen free -Parenterals Preparation 4. Sterile water for injection Sterilizes and suitably packed -No antimicrobial added -Parenterals Preparation 5. Bacteriostatic water for injection Sterile water contain one or more suitable anti microbial - Parenterals PreparationApproaches to improve aqueous solubility: Approaches to improve aqueous solubility Co-solvency pH control Solubilization (macrogol ethers, polyoxyethylated sorbitan, sucrose monoesters, lanolin esters) Complexation Chemical modification Particle size controlb. Non-aqueous vehicles: b. Non-aqueous vehicles Fixed oils of vegetable origin Alcohols Polyhydric alcohols Dimethylsulfoxide Ethyl ether Liquid paraffin Miscellaneous solvents1. Fixed oils of vegetable origin : 1. Fixed oils of vegetable origin These are non-volatile oils that consist mainly of fatty acid esters of glycol. Almond oil, consist of glycerides mainly of oleic acid is used as a solvent for oilyphenol injections Arachis oil is used as the solvent in dimercaprol injection. Olive oil, sesame oil, maize oil, cottonseed oil, soya oil and caster oil are all suitable for parenteral and eye, ear drop formulation. Ethyl oleate is useful solvent for both ergocalciferol injection and testosterone propionate injection. Vegetable oils are also used for veterinary formulations.PowerPoint Presentation: Sr . No. Name Properties Remarks 1 Corn oil -Clear -Light yellow oily liquid -Solvent and vehicle for injection 2. Cotton seed oil -Pale yellow oily liquid -Odourless -Solvent and vehicle for injection 3. Peanut oil -Colourless to Pale yellow -Solvent and vehicle for injection -- Liniments 4. Sesame Oil -Pale Yellow -Odourless - Solvent and vehicle for injection - Cosmetics, liniments and ointments. 5. Ethyl Oleate -Pale yellow oily liquid Low viscosity Vehicle for I.M, 6. Silicons Different Grade Dermatological Preparations2. Alcohols : 2. Alcohols Ethyl alcohol is the most widely used solvent in this class, particularly for external preparation, where it evaporates and produce a cooling effect Ex: salicylic acid lotion At concentrations greater than 15%, ethanol exhibits anti microbial activity but because of its toxicity, it is used orally or parenterally only at low concentrations, usually as a co solvent with water. In some case isopropyl alcohol is also used externally as a solvent.3. Polyhydric alcohols: 3. Polyhydric alcohols Alcohols containing two hydroxyl groups per molecule are known as glycols but because of their toxicity, they are rarely used internally. Propylene glycol is only the exception. It is often used in conjunction with water or glycerol as a cosolvent. It is used n formulation of digoxin inj, phenobarbital inj etc preparation. They are used with various range like PEG 400, PEG 600 etc. Glycerols an alcohol possessing three hydroxyl groups per molecule, is also used as a cosolvents with water for oral use.PowerPoint Presentation: Sr . No. Name Properties Remarks 1 Ethanol -Miscible wit hwater -Antimicrobial Property -Costly due to high excise duty 2. Propylene Glycol -solvent as well as preservatives - miscible with water -Oral Preparation -Hydrophilic ointments - injection of barbiturates,iodine 3. Glycerol -Colorless -Syrupy -Sweet taste -Hygroscopic Use as -solvent -Preservative -Humectant -Use in throat paints, linctuses, syrups, Elixirs 4. 1,3 butylene glycol -Colourless -Viscous -Miscible with water - solvent for morphine injection 5. Polyethylene glycol -colourless -Used in lotion 6. Sorbitol -white -miscible with water -sweet taste -70% w/w used as vehiclePowerPoint Presentation: 4. Dimethylsulfoxide This is highly polar compound and is thought to aid the penetration of drugs through the skin, used as a solvent for veterinary drugs, and as a permeation enhances for transdermal system. 5. Ethyl ether: Widely used for the extraction of crude drugs. Not used internally Used as a cosolvent with alcohol in some collodion.PowerPoint Presentation: 6. Liquid paraffin: The oily nature makes its unplease so used externally. It is used as a solvent fot the topical application of drugs in emulsion formulations. It was widely used as the base for nasal drops. 7. Miscellaneous solvents: Isopropyl myristate, isopropyl palmitate used in cosmetics. Dimethylformamide, dimethylacetamide use as solvent in veterinary preparation. Xylene is present in some ear drops for human use to dissolve ear wax.2. BUFFERS: 2. BUFFERS These are materials which when dissolved in a solvent will enable the solution to resist any changes in pH. The choice of buffer depends on the pH and buffering capacity required. It must be compatible with other excmipient and have a low toxicity. Pharmaceutical buffers are carbonates, citrates, gluconates, lactates, phosphates or tartrates. As the pH of body fluid is 7.4, products such as injections, eye drops and nasal drops should be buffered at this value to avoid irritation.3. DENSITY MODIFIERS: 3. DENSITY MODIFIERS It is rarely necessary to control the density if solutions except when formulating spinal anesthetics. Fluid present in cerebrospinal is isobaric in nature. So, solution of lower density than cerebrospinal cause problem is hypobaric and with high density called hyperbaric.. So, the solution should be made isobaric with particular density.4. ISOTONICITY MODIFIERS: 4. ISOTONICITY MODIFIERS Solution for injection, for application to mucous membranes are large volume solutions for ophthalmic use should be made isotonic with tissue fluid to avoid pain and irritation. Dextrose and sodium chloride are largely use to adjust the tonicity.5. VISCOSITY ENHANCEMENT: 5. VISCOSITY ENHANCEMENT It may be difficult for aqueous based topical solutions to remain in place on the skin or in eyes for any significant time because of their low viscosity. To counteract this effect, low concentrations of gelling agents can be used to increase the apparent viscosity of the product. Ex: povidone, HPMC, HEC and carbomer.6. REDUCING AGENTS AND ANTI-OXIDANTS: 6. REDUCING AGENTS AND ANTI-OXIDANTS The decomposition of pharmaceutical products by oxidation can be controlled by the addition of reducing agents such as sodium metabisulphite or antioxidants such as butylated hydroxyanisole or butylated hydroxytoluene, butyrated hydroxyacetate or pthalate.7. PRESERVATIVES: 7. PRESERVATIVES In recent years, adequate preservation of liquid products has increased in importance. Source of contaminations are raw materials, processing containers and equipments, the manufacturing environment, operators, packaging material etc. An ideal preservative can be qualitatively meet the following criteria 1. It must be effective against a broad spectrum of microorganisms. 2. It must be nontoxic, nonsensitizing, adequately soluble, compatible and acceptable with respect to taste and odor.PowerPoint Presentation: Sr. No Class Usual concentration (%) 1 ACIDIC Phenol Chlorocresol O-phenyl phenol Alkyl esters of parahydroxybenzoic acid Benzoic acid and its salts Boric acid and its salts Sorbic acid and its salts 0.2-0.5 0.05-0.1 0.005-0.01 0.001-0.2 0.1-0.3 0.5-1.0 0.05-0.2 2 NEUTRAL Chlorobutanol Benzyk alcohol B- phenylethyl alcohol 0.5 1.0 0.2-1.0 3 MERCURIAL Thimerosal Phenylmercuric acetate and nitrate Nitromersol 0.001-0.1 0.002-0.005 0.001-0.02 4 QUARTERN ARY AMMONIUM COMPOUNDS Benzalkonium chloride Cetylpyridinium chloride 0.004-0.02 0.01-0.028. SWEETENING AGENTS:: Sucrose Sorbitol (Half Sweet than Sucrose) Glycerin Honey Saccharin Sodium (300-550 times) Cyclametaes (30 times sweeter than sucrose) Aspartame 8. SWEETENING AGENTS:PowerPoint Presentation: Low molecular weight carbohydrates like sucrose are traditionally used sweetining agents. Sucrose has advantage of being colourless, very soluble in water, stable over a pH range of about 4-8 and increases the viscosity of fluids. Only six artificial flavours are permitted for oral use within the European union are sodium or calcium salt of saccharin, aspartame comounds like L- aspartic acid and L- phenylalanine, acesulfame potassium, thaumatin, sodium cyclamide and neohesperidine.9. FLAVOURING AGENTS:: 9. FLAVOURING AGENTS: The use of flavour is actually a composite sensation of taste, touch, smell, sound and heat. All above mensioned factors involve a combination of physiochemical and psychological action influence the sensitivity of substances. There are simply four types of tastes - Sweet - Sour - Salty -Bitter And some others are a combination of the above. Similarly there are seven basic odours like - Ethereal - camphoraceous - Musky - Floral - Pepperminty -Pungent -PutridClassification of flavouring agents: : Classification of flavouring agents: Two Types: 1. Natural and 2. Synthetic Natural a. Fruits (Sweet, Sur and Astringent) -Citrus Fruits (Orange, Lemon) - Rasberry and Strawberries b . Seeds (Vanilla, Anise, Nutmeg) c. Buds/ Flawers -Orange flower water - clove blossoms d. Leaves - Camomile -Thyme - RosemaryPowerPoint Presentation: e. Roots Glycyrrhiza f. Barks/Stems White pine Cinnamon Wild Cherry Bark g. Woods Quassia h. Gums Gum arabic Gum Tragacanth2. Synthetics : 2. Synthetics SR . NO. SYNTHETICS NATURE OF FLAVOUR 1. Benzaldehyde Bitter Almond, Cherry pits 2. Decyl Aldehyde Citrus Flavours (Orange, Lemon) 3. Cinnamic aldehyde Cinnamon type 4. Ionones Berry type flavours 5. Ethyl aceto acetate Cherry flavor 6. Terpene Alcohols Rasberry , strawberry and pineapple 7. Ethylmalonate Wine like flavourPowerPoint Presentation: Sr No Taste of product Suitable masking flavour 1 Sour Citrus flavour 2 Salty Butterscotch, apple and citrus 3 Bitter Chocolate, mint, raberry 4 Sweet Fruit, Berry, Vanilla10. Coloring agents: 10. Coloring agents1. Natural Colouring Agents: 1. Natural Colouring Agents ( A) Plants: Many plants contain colouring agents which may be extracted. And used as colorant. Some Examples are: a. Chlorophyll-green b. Annatto seeds-yellow to orange c. Carots -yellows d. Madder Plant-Reddish Yellow e. Indigo-Blue f. Saffron-Yellow g. Caramel- Burnt SugarPowerPoint Presentation: (B) Animal: Cochineal: It is an alkaline solution of the soluble Colouring principles caraminic acid of chochineal insects preserved by the addition of glyccerin . It is very dark purplish red liquid. b. Carmine: It is the aluminium lack of the colouring principle obtained from cochineal. It gives red colour to aqueous solution.PowerPoint Presentation: (C) Minerals: Mineral colours are termed pigments. They are used to colour lotions, cosmetics and other preparation for external application. As they are toxic, their use for internal preparation is forbidden. Ex: Red ferric oxide Yellow Ferric Dioxide Titanium dioxide Carbon Black.2. Synthetic colouring agents: 2. Synthetic colouring agents The sysnthetic colours are coaltar dyes, because many of them are produced from substance obtained from coal-tar. The certified colours are classified into three groups: Group I- F.D. and C. Colours used in foods, drugs and cosmetics. Groups II- The D. and C. Colour used in drug and Cosmetics. Group III- The External D. and C. Colour. Any color found in any of these lists is spoken as permitted color like Blue - Brilliant Blue, Indigo Carmine Green - Fast green, Guinea Green Violet - Wood Violet Red- Amaranth, Erythrosin Scarlet red Yellow - Tartrazine, Sunset YellowManufacturing : Manufacturing \1. Raw material: 1. Raw material The raw material used for the manufacturing of pharmaceutical are as per the standard specification. These specifications should assure identity, purity, uniformity and freedom from excessive microbial contamination. Incoming raw material should be thoroughly tested before they are released for manufacturing. Additional processing may be necessary to obtained a desirable property, such as particle size or microbial contamination. Aside from the active ingredient, water is usually the most important constituent in a liquid products.PowerPoint Presentation: It should meet the USP requirement for purified water and obtained by ion exchange or distillation. To prevent microbial growth, various techniques employed include reverse osmosis purification, U.V. sterilization, membrane filtration and constant circulation in piping systems that have no dead ends where microorganism grow.2.Equipment: 2.Equipment The type of equipment used in the manufacture of oral solutions consists of mixing tanks equipped with a means of agitation, measuring devices for large and small amounts of solids and liquids, and a filtration system for the final polishing and or sterilization of the solution. All equipment must be thoroughly cleaned and sanitized before use. Appropriate disinfectants, include dilute solutions of hydrogen peroxide, phenol derivatives and peracetic acid. Equipment and lines can be sterilized by such methods as alcohol, boiling water, autoclaving, steam or dry heat.PowerPoint Presentation: Tanks are usually constructed of polished stainless steel and are usually jacketed to allow for heating or cooling of the contents. They can be obtained in a number of different sizes. If tanks are use for the compounding of the bulk liquid, they have a built in agitation system. Water condensate that forms on the lid of mixing tanks and during heating and chilling steps may provide a source of microbial contamination that is often overlloked.PowerPoint Presentation: The liquid is ten clarified by cycling through a filtration system and the polished solution is stored in an adjacent tank until released by the Q.C. dept. The liquid may then be transported to the filling line, either manually by filling into portable transport tanks or by pumping through suitable liquid delivery system. The distance should be less to prevent microbial growth. A major source of microbial contamination is often the processing operators. Head covering should be worn all times while gloves and face mask should be worn as necessary.Compounding procedure: Compounding procedure Dilute solutions prepared from rapidly dissolving materials, are simply prepared by charging the solute to the solvent and agitating until the solution is homogeneous. When more concentrated solutions are being made, or when the solute is slowly dissolving, it may be advantageous to employ heat. Ex: Syrup. During compounding the less dissolved substance should be preheated and than use. All the Excipient should be added step by step in the preparation. Dyes and flavours should be also predissolved. The active medicaments should be dissolved at last.Filling and Packaging: Filling and Packaging The specific method used for filling a pharmaceutical liquid varies greatly depending on the characteristics of liquid, the type of package into which the liquid is placed and the required production output. Three basic filling methods like gravimetric, volumetric and constant level are used for most liquid filling operations. Gravimetric filling works on the principle of gravitational force but rarely used.PowerPoint Presentation: Volumetric filling is usually accomplished by positive displacement piston action. Each filling station is equipped with a measuring piston and cylinder The fill accuracy is controlled by the close tolerances to which the pistons and cylinders are manufactured. The fill amount is measured by the stoke of piston, which on all machine can be varied to a limited degree. This type of device is capable of accuracy to within fraction of milliliter. Volumetric filling encountered a problem when the product is viscous or less dense.Bottle filling machine : Bottle filling machine Packing conveyor beltPowerPoint Presentation: Constant level filling uses the container as the means for controlling the fill of each unit. The fill amount is varied by adjusting the height to which the container is filled. The latest filling machine used is called vacuum filling. To fill by vacuum, a seal must be made between the filling head and the container, which causes the liquid to flow from the bulk liquid tank to the container. A vacuum is then developed within the container which causes the liquid to flow from the bulk liquid tank to the container.PowerPoint Presentation: Generally glass or plastic materials are used as a packaging material for the liquid dosage forms. Before using glass or plastic materials, They should not react with the excipient or drug. Packaging material should be compatible with the solution.Evaluation Parameters: Evaluation Parameters Appearance pH Viscosity Specific gravity Microbial count Leakage test for filled bottle (By using plastic vacuum dessicator) Check the cap sealing Fill volume determination Particulate matter testing Water vapour permeability test Stress testSuspension: Suspension Pharmaceutical suspensions may be defined as coarse dispersions in which insoluble solids are suspended in a liquid medium. Stokes relation describe the settling rate of particle in suspension, V= D 2 ( ρ 2 – ρ 1) g 18 ηSuspension Formulation: Suspension Formulation 1. Aggregated systems 2. dispersed systems 3.Rheologic considerations 4.Formulation Adjuvant 5.Preparative techniquesPowerPoint Presentation: · Components Function API Active drug substances Wetting agents They are added to disperse solids in continuous liquid phase. Flocculating agents They are added to floc the drug particles Thickeners They are added to increase the viscosity of suspension. Buffers and pH adjusting agents They are added to stabilize the suspension to a desired pH range. Osmotic agents They are added to adjust osmotic pressure comparable to biological fluid. Coloring agents They are added to impart desired color to suspension and improve elegance. Preservatives They are added to prevent microbial growth. External liquid vehicle They are added to construct structure of the final suspension.Evaluation of suspension: Evaluation of suspension Sedimentation volume Particle size change Electrokinetic method/Zeta Potential measurement Appearance Color, odor and taste Redispersibility and Centrifugation tests Rheological measurement Stress test pH Freeze-Thaw temperature cycling1. Sedimentation volume: 1. Sedimentation volumeBrief introduction of Extract, Tincture and infusion: Brief introduction of Extract, Tincture and infusion Infusions, extracts and tinctures are terms used for concentrated solutions of active principles from animal or vegetable sources. Infusion: Infusions are prepared by extracting the drug using 25% alcohol but without the application of heat. Traditionally these preparations are then diluted 1:10 in the final products.Extracts:: Extracts: An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol or water. Extracts are similar products that are then concentrated by evaporations.Tinctures: Tinctures A tincture is an alcoholic extract (e.g. of leaves or other plant material) or solution of a non-volatile substance (e.g. of iodine, mercurochrome). To qualify as a tincture, the alcoholic extract is to have an ethanol percentage of at least 40-60%. Tinctures are alcoholic extracts of drugs but are relatively weak compared with extracts. General method of preparation Herbs are put in a jar and a spirit of 40% pure ethanol is added. The jar is left to stand for 2–3 weeks, shaken occasionally, in order to maximize the concentration of the solution. To make a more precise tincture, more extensive measuring can be done by combining 1 part herbs with a water-ethanol mixture of 2-10 parts, depending on the herb itself. With most tinctures, however, 1 part water at 5 parts ethanol is used.PowerPoint Presentation: Examples that were formerly common in medicine include: Tincture of Cannabis sativa Tincture of Benzoin Tincture of cantharides Tincture of ferric citrochloride (a chelate of citric acid and Iron(III) chloride) Tincture of green soap Tincture of iodine Tincture of opiumEMULSION: 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: MilkPowerPoint 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 EmulsionDetermination 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 emulsionPREPRATION 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 emulsionPowerPoint 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. A mucilage is first form by triturating the gum with water.(1parts gum and 2 parts water). Triturate untill a musilage is formed. The oil is then added in small proportions with continuous trituration . After the primary emulsion has been formed, the trituration should be continuous for five minutes before it is diluted with water. This method is slower and not reliable as dry gum method.PowerPoint Presentation: 3. Bottle Method: It is modification of dry gum mthod.1 parts of acacia is mixed with 2 parts of volatile oil by shaking in a bottle. Two parts of water are added all at once and shaking continued, until emulsion is formed. The remaining water is then added in small portions with shaking. This method is suitable for volatile oils and non-viscous oils.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 1Formulation of emulsion: Formulation of emulsion For the formulation of emulsion, both the physical and chemical parameters to be consider. Physical Parameters. 1. Heat 2.TimingEquipment for emulsification: Equipment for emulsification Mechanical stirrers Homogenizers Ultrasonifiers Colloid mills Homogenizer Mechanical Stirrer Ultrasonifiers Colliod millsColloid mills : Colloid millsChemical parameters: Chemical parameters Chemical stability Safety Choice of lipid phase Choice of emulsifying agents Choice of surfactants Choice of antimicrobial preservatives choice of antioxidantsPowerPoint Presentation: Sr. No Class Usual concentration (%) 1 ACIDIC Phenol Chlorocresol O-phenyl phenol Alkyl esters of parahydroxybenzoic acid Benzoic acid and its salts Boric acid and its salts Sorbic acid and its salts 0.2-0.5 0.05-0.1 0.005-0.01 0.001-0.2 0.1-0.3 0.5-1.0 0.05-0.2 2 NEUTRAL Chlorobutanol Benzyk alcohol B- phenylethyl alcohol 0.5 1.0 0.2-1.0 3 MERCURIAL Thimerosal Phenylmercuric acetate and nitrate Nitromersol 0.001-0.1 0.002-0.005 0.001-0.02 4 QUARTERN ARY AMMONIUM COMPOUNDS Benzalkonium chloride Cetylpyridinium chloride 0.004-0.02 0.01-0.02List of antioxidents: List of antioxidents Gallic acid Propyl gallate Ascorbic acid Ascorbyl palmitate Sulfites L- Tocopherol BHA BHTEvaluation/Stability of emulsion: Evaluation/Stability of emulsion Creaming Flocculation Coalescence Phase separation Viscosity Electrophoretic properties Particle size number analysis Stress condition like aging and temperature, Centrifugation You do not have the permission to view this presentation. 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