LIQUID DOSAGE FORMS

Prepared By : Mr. Naresh Rajgor, Assistant Professor, M.P. Patel College of Pharmacy, Kapadwanj
LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

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
1. Solution

2. Syrup

3. Suspension

4. Emulsion

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.

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.

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CLASSIFICATION

ADDITIVES USED IN LIQUID DOSAGE FORMS 1. Vehicles 2. Buffers 3. Density modifiers 4. Stabilizer 5. Isotonicity modifiers 6. Viscosity enhancement 7. Preservatives 8. Sweetening agents 9. Reducing agents and antioxidants 10. Flavors and perfumes 11. Colors LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

1. VEHICLES: Two types of vehicles; a. Aqueous vehicles b. Non- 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.

Types of pharmaceutical water. Sr .. Name Water Properties -Cheap -High Dielectric Constant -Miscible with alcohol, glycerol and other polar solvents -Non flammable -Inert -Prepared by Distillation or ion exchange resin -Sterile -Pyrogen free Remarks -Impurities

Purified Water Water for injection

-used for Parenterals Preparation -Parenterals Preparation -No antimicrobial added -Parenterals Preparation -Parenterals Preparation

Sterile water for injection Sterilizes and suitably packed

Bacteriostatic water for injection

Sterile water contain one or more suitable anti microbial

Approaches to improve aqueous solubility Co-solvency pH control PREPARED BY: MR. NARESH

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Solubilization (macrogol ethers, polyoxyethylated sorbitan, sucrose monoesters, lanolin esters) Complexation Chemical modification Particle size control

b. Non-aqueous vehicles 1. Fixed oils of vegetable origin 2. Alcohols 3. Polyhydric alcohols 4. Dimethylsulfoxide 5. Ethyl ether 6. Liquid paraffin 7. Miscellaneous solvents

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. PREPARED BY: MR. NARESH

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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. Name Properties Remarks

Sr . No. 1

Corn oil

-Clear -Light yellow oily liquid -Pale yellow oily liquid -Odourless -Colourless to Pale yellow -Pale Yellow -Odourless

-Solvent and vehicle for injection

2.

Cotton seed oil

-Solvent and vehicle for injection

3.

Peanut oil

-Solvent and vehicle for injection -- Liniments - Solvent and vehicle for injection - Cosmetics, liniments and ointments. Vehicle for I.M,

4.

Sesame Oil

5.

Ethyl Oleate

-Pale yellow oily liquid Low viscosity Different Grade

6.

Silicons

Dermatological Preparations

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. PREPARED BY: MR. NARESH

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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.

Sr.No. Name 1 2. Ethanol Propylene Glycol

Properties -Miscible wit hwater -Antimicrobial Property -solvent as well as preservatives - miscible with water -Colorless -Syrupy -Sweet taste -Hygroscopic

Remarks -Costly due to high excise duty -Oral Preparation -Hydrophilic ointments - injection of barbiturates,iodine Use as -solvent -Preservative -Humectant -Use in throat paints, linctuses, syrups, Elixirs - solvent for morphine injection

3.

Glycerol

4.

1,3 butylene glycol -Colourless -Viscous -Miscible with water Polyethylene glycol -colourless Sorbitol -white -miscible with water -sweet taste

5. 6.

-Used in lotion -70% w/w used as vehicle

4. Dimethylsulfoxide LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

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.

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 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

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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 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 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

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 LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

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.

Sr . No 1

Class

Usual concentration (%) 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 0.5 1.0 0.2-1.0 0.001-0.1 0.002-0.005 0.001-0.02 0.004-0.02 0.01-0.02

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 NEUTRAL Chlorobutanol Benzyk alcohol B- phenylethyl alcohol MERCURIAL Thimerosal Phenylmercuric acetate and nitrate Nitromersol QUARTERN ARY COMPOUNDS Benzalkonium chloride Cetylpyridinium chloride AMMONIUM

8. SWEETENING AGENTS: 1. Sucrose

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2. Sorbitol (Half Sweet than Sucrose) 3. Glycerin 4. Honey 5. Saccharin Sodium (300-550 times) 6. Cyclametaes (30 times sweeter than sucrose) 7. Aspartame

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 Lphenylalanine, acesulfame potassium, thaumatin, sodium cyclamide and neohesperidine.

8. 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 LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

- Ethereal - Floral

- camphoraceous -Pepperminty

- Musky -Pungent -Putrid

Classification of flavouring agents: Two Types: 1. Natural and 2. Synthetic 1. 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 e. Roots - Glycyrrhiza f. Barks/Stems - White pine -Cinnamon -Wild Cherry Bark g. Woods - Quassia h. Gums - Gum arabic - Gum Tragacanth

- Rosemary

2. Synthetics
SR . NO. SYNTHETICS 1. 2. 3. Benzaldehyde Decyl Aldehyde NATURE OF FLAVOUR Bitter Almond, Cherry pits Citrus Flavours (Orange, Lemon)

Cinnamic aldehyde Cinnamon type PREPARED BY: MR. NARESH

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4. 5. 6. 7.

Ionones Ethyl aceto acetate Terpene Alcohols Ethylmalonate

Berry type flavours Cherry flavor Rasberry, strawberry and pineapple Wine like flavour

Sr No Taste of product 1 2 3 4 Sour Salty Bitter Sweet

Suitable masking flavour Citrus flavour Butterscotch, apple and citrus Chocolate, mint, raberry Fruit, Berry, Vanilla

10. Coloring 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 PREPARED BY: MR. NARESH

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d. Madder Plant-Reddish Yellow e. Indigo-Blue f. Saffron-Yellow g. Caramel- Burnt Sugar (B) Animal:

a. 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.

(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 The synthetic colours are coaltar dyes, because many of them are produced from substance obtained from coal-tar. The certified colours are classified into three groups: PREPARED BY: MR. NARESH

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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 Yellow

MANUFACTURING OF LIQUID DOSAGE FORMS:

WASHING STORAGE

I D O R

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.

WASHED BOTTLE

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FILLING & SEALIN

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. 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
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. 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.

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. PREPARED BY: MR. NARESH

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Head covering should be worn all times while gloves and face mask should be worn as necessary.

3. 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.

4. 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. 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

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PACKING CONVEYOR BELT

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. 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
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 test

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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= D2(2 1) g 18

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Properties of an Ideal Suspension are:

Uniform dispersion Palatable Pleasing odor and color No grittiness Easy to pour yet not watery No cap-lock Temperature insensitive Particles should settle slowly Formulation should allow the easy redispersionof sedimentedparticles A flocculated suspension is desirable than a deflloculatedsuspension A suspension should not be too viscous to reduce the sedimentation rate

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SUSPENSION FORMULATION

1. Aggregated systems 2. dispersed systems 3.Rheologic considerations 4.Formulation Adjuvant 5.Preparative techniques Components
API Wetting agents Flocculating agents Thickeners

Function
Active drug substances They are added to disperse solids in continuous liquid phase. They are added to floc the drug particles They are added to increase the viscosity of suspension.

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Buffers They are added to stabilize the suspension to a desired pH range. and pH adjusting agents Osmotic agents They are added to adjust osmotic pressure comparable to biological fluid. Coloring agents Preservatives They are added to impart desired color to suspension and improve elegance. They are added to prevent microbial growth.

External liquid vehicle They are added to construct structure of the final suspension.

Packaging and Storage of Suspensions:

1)Should be packaged in wide mouth containers having adequate air space above the liquid. 2) Should be stored in tight containers protected from: freezing. excessive heat & light. 3) Label: "Shake Before Use" to ensure uniform distribution of solid particles and thereby uniform and proper dosage.

Evaluation of suspension

(Read from Lachmann for detail)

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 cycling

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1. Sedimentation volume

Examples of Pharmaceutical Suspensions: 1. Antacid oral suspensions 2. Antibacterial oral suspension 3. Dry powders for oral suspension (antibiotic) 4. Analgesic oral suspension 5. Anthelmenticoral suspension 6. Anticonvulsant oral suspension 7. Antifungal oral suspension

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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

Types of emulsion: 1. Oil in water (O/W): (Oral use) 2. Water in Oil (W/O): (External use) 3. Micro emulsion (transparent emulsion): The property of transparency is due to the small particle size of the dispersed phase (0.05 microns). 4. 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

Determination of emulsion type Test Observation Comments liquid

1. Dilution Test Emulsion can be diluted with onlyUseful for (Miscibility) external phase emulsions only

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o/w emulsion can be diluted with water.

w/o emulsion can be diluted with oil.

Test 2. Dye Test (Staining)

Observation 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.

Comments May fail if ionic emulgents are present.

3. CoCl2 Filter Filter paper impregnated with CoCl2 dried (Blue)

Paper 4. Fluorescence Test

changed to pink when O/W emulsion is added. 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

A. If emulsion creams are upward the emulsion is O/W type. B. If the emulsion creams are downward it is W/O type emulsion.

6. Conductivity Test

Water conduct an electric current wile oils do not. Fails in non ionic O/W emulsion

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PREPRATION OF EMULSION
1. 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.

E u ifie m ls p rfe tly e c

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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.

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.

Types of oils Examples

1. Fixed oils Almond oil Arachis oil Castor oil Cod liver oil Liquid paraffin Turpentine oil Cinnamon Peppermint Male fern Extract

Qty for primary emulsion Oil

4

Water
2

Gum
1

2. Mineral oil 3. Volatile oil

3 2

2 2

1 1

4. Oleo-resin

FORMULATION OF EMULSION/ MANUFACTURING OF EMULSION

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 For the formulation of emulsion, both the physical and chemical parameters to be consider. Physical Parameters. 1. Heat 2.Timing

E q
Chemical parameters (Read lachmann for detail) Chemical stability
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Mca eh

Safety Choice of lipid phase Choice of emulsifying agents Choice of surfactants Choice of antimicrobial preservatives choice of antioxidants EMULSIFYING AGENTS and SURFACTANT

ANTIMICROBIAL PRESERVATIVES Sr. No Class Usual concentration (%)

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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 NEUTRAL Chlorobutanol Benzyk alcohol B- phenylethyl alcohol MERCURIAL Thimerosal Phenylmercuric acetate and nitrate Nitromersol QUARTERN ARY AMMONIUM COMPOUNDS Benzalkonium chloride Cetylpyridinium chloride

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 0.5 1.0 0.2-1.0 0.001-0.1 0.002-0.005 0.001-0.02 0.004-0.02 0.01-0.02

LIST OF ANTIOXIDENTS Gallic acid Propyl gallate Ascorbic acid Ascorbyl palmitate Sulfites L- Tocopherol BHA BHT

EVALUATION/STABILITY OF EMULSION Creaming

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 Flocculation Coalescence Phase separation Viscosity Electrophoretic properties Particle size number analysis Stress condition like aging and temperature, Centrifugation

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MICROEMULSIONS
Microemulsions are thermodynamically stable , optically transparent, isotropic dispersions of aqueous and hydrocarbon liquids stabilized by an inter facial film of surfactant molecules. Microemulsion sare monodispersed spherical droplets (diameter <100nm) of water in oil or oil in water, depending on the nature of the surfactant.

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Microemulsions are formed because ...

The penalty for the apparent increase in free energy is compensated by the lowering of IFT to ultra low levels (10-2 10-3mN/m)

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 The work done in lowering IFT is achieved through a gain in system entropy S due to the creation of a large number of sub-micron sized droplets All this occurs when at molecular levels, surfactants form the most condensed interfacial film between oil and water.

MULTIPLE EMULSION
These are known as double emulsion These are more complex systems, as the drops of the dispersed phase contain even smaller dispersed droplets, in most vases identical with the continuous phase, but separated physically from the continuous phase. These are known as Emulsion of Emulsion meansmultiple emulsion. Based on nature of the dispersed medium multiple emulsion classifiedas follows 1.O/W/O emulsion 2.W/O/W emulsion 1. O/W/O emulsion: In O/W/O system , an aqueous phase separates internal and external phase. It is a system in which water droplets are surrounded in oil phase ,which in true encloses one or more oil droplets. LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

2. W/O/W emulsion: In W/O/W sytem, an organic phase separates internal and external phase. it is a system in which oil droplets may be surrounded by aqueous phase, which in turn one or several water droplets. Advantages Remarkable degree of biocompatibility Complete biodegradability Hydrophilic and hydrophobic drugs can be entrapped Protection from inactivation by the endogenous factors Increase in drug dosing interval Taste masking of bitter drugs Disadvantages Short life packed in a plastic or glass container so, care should be taken during handling and storage.

Preparation
Methods of preparations: Sonication Agitation Phase inversion Great care must be taken during preparation of final system. However, because vigroustreatments employed for preparations of primary emulsions will often break the primary emulsion, this result in loss of phase identity. Two different surfactants of different nature are used. One surfactant stabilizes the lipophilicemulsion, while other stabilizes the hydrophilic emulsion. Emulsifiers get absorbed at the surface of droplets during formation of emulsion and prevent them from drawing close enough to aggregate. Multiple emulsions are preapered by various methods 1)Two step emulsification LIQUID DOSAGE FORMS RAJGOR PREPARED BY: MR. NARESH

2)Modified two step emulsification 3)Phase inversion 4)Membrane emusificationmethod 5)Micro channel emulsification Evaluation of multiple emulsion 1)Characterization 2)Average globule size and size distribution 3)Number of globules 4)Percentage of drug entrapment 5)Rheological evaluation 6)Zeta potential 7)In-vitro stability studies 8)In-vitro drug release Application of multiple emulsions 1)Controlled and sustained drug delivery 2)Drug targeting 3)Vaccine adjuvant 4)Enzyme immobilizatoin BRIEF INTRODUCTION OF EXTRACT, TINCTURE AND INFUSION EXTRACT

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. Extraction involves the separation of active portion of plant or animal tissues from the inactive components through the use of selective solvent which are known as Galenica. A medicinal preparation composed mainly herbal or vegetable matter prepared by extraction of crude vegetable drugs with suitablesolvents. Menstum:Solvent used for extraction( eg, water alcohol, ether) Marc:The innertfibrous and other insoluble materials remaining after extraction. Extracts are preparation of liquid( liquid extractaand tinctures), semisolid(soft extracts) or solid consistancyobtain from herbal drugs or animal matter. Liquid extracts: PREPARED BY: MR. NARESH

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They are liquid preparations of which, in general, one part by mass or volume is equivalent to 1 part by mass of the dry herbaldrug or animal. Liquid extracts are prepared by using ethanol of a suitable concentration or water to extract herbal drug or animal matter, or by dissolving a soft or dry extract of herbal drug or animal matter in either ethanol of a suitable concentration or water.

Soft extract: They are semisolid preparation obtained by evaporation of the solvent use for extraction. Dry extract: They are solid preparations obtained by evaporation of the solvent use for their production and have lod or water content of not more than 5%m/m. INFUSION

They are dilute solutions containing readily soluble constituents of crude drugs. It involves pouring water over the drugs and then allowing it to keep in contact with water.(15 min) with stirring and finally filtering of the liquid.

Fresh infusion is prepared by macerating the drug for a shorperiod of time with cold or hot water.

Concentrated infusions are prepared by modified percolation and maceration process. Infusion pot Consist of covered jar( made up of earthenware stainless-still, ceramic, glass, porcelain)which is fitted at certain height a perforated tray upon which the crude may be allowed to rest in water being pour over it.

The drug may be enclosed loosely in a small muslin bag and suspended in the jar at a height were it will be just covered by the liquid. The perforated tray or muslin bag confers to advantages. 1.Complete extraction because when the menstrumsurrounding the drug becomes saturated it will sinks to the bottoms due to its increased density and another amount of fresh menstrumdisplaced it leading to circulatory diffusion.

2.At the end of infusion time, the drug can be lifted out, leaving clear liquid which can be strained quickly. Fresh (Dilute) Infusion

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PREPARED BY: MR. NARESH

A fresh infusion is an aqueous solution of active constituents of a vegetable drug prepared by the process of infusion. Water is used as menstrum. Fresh infusion should be used within 12 hours after its preparation because it gets spoiled due to bacterial and fungal growth. E.g. Fresh infusion of quassia Concentrated (stock) infusion Prepared by double or triple maceration. Eight times stronger than fresh infusion. Alcohol in the concentration of 20-25% is used DECOCTION In this process, the crude drug is boiled in a specified volumof water for a defined time(10 min); it is then cooled and strained or filtered. This procedure is suitable for extracting water soluble, heat stable constituents and drugs of hard and woody nature. This process is typically used in preparation of ayurvedicextracts called quath or kawath. The starting ratio of crude drug to water is fixed, e.g. 1:4 or 1:16, the volume is then brought down to its original volume by boiling during the extraction procedure. Then the concentrated extract it filtered and use as such for processed further.
Infusion Decoction
Hard woody structure Hot water Boiling the drug with menstrum Calculated as soon as water begin to boil Adjustment required Ant covered apparatus Use fresh Soft structure Cold or hot water Infusing the drug with menstrum Calculated as soon as water is added to drug No adjustment Earthenware pot Use within 12 hrs

1-Plant 2-Menstrum 3-Procedure 4-time 5-adjustment of final volume 6-appartus 7-storage

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 PREPARED BY: MR. NARESH

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Herbs are put in a jar and a spirit of 40% pure ethanol is added. The jar is left to stand for 23 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. 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 opium

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PREPARED BY: MR. NARESH