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LIQUID DOSAGE FORMS

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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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 PREPARED BY: MR. NARESH RAJGOR


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 Properties Remarks


Water -Cheap -Impurities
-High Dielectric Constant
-Miscible with alcohol, glycerol and
other polar solvents
-Non flammable
-Inert
Purified Water -Prepared by Distillation or ion -used for Parenterals
exchange resin Preparation
Water for injection -Sterile -Parenterals Preparation
-Pyrogen free
Sterile water for injection Sterilizes and suitably packed -No antimicrobial added
-Parenterals Preparation

Bacteriostatic water for Sterile water contain one or more -Parenterals Preparation
injection suitable anti microbial

 Approaches to improve aqueous solubility


 Co-solvency
 pH control

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


 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.
• 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.

Sr . Name Properties Remarks


No.

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


1 Corn oil -Clear -Solvent and vehicle for injection
-Light yellow oily
liquid
2. Cotton seed oil -Pale yellow oily -Solvent and vehicle for injection
liquid
-Odourless
3. Peanut oil -Colourless to Pale -Solvent and vehicle for injection
yellow -- Liniments

4. Sesame Oil -Pale Yellow - Solvent and vehicle for injection


-Odourless - Cosmetics, liniments and
ointments.

5. Ethyl Oleate -Pale yellow oily Vehicle for I.M,


liquid
Low viscosity
6. Silicons Different Grade 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.

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 Properties Remarks

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


1 Ethanol -Miscible wit hwater -Costly due to high excise duty
-Antimicrobial Property
2. Propylene Glycol -solvent as well as -Oral Preparation
preservatives -Hydrophilic ointments
- miscible with water - injection of barbiturates,iodine

3. Glycerol -Colorless Use as


-Syrupy -solvent
-Sweet taste -Preservative
-Hygroscopic -Humectant
-Use in throat paints, linctuses, syrups,
Elixirs
4. 1,3 butylene glycol -Colourless - solvent for morphine injection
-Viscous
-Miscible with water

5. Polyethylene glycol -colourless -Used in lotion


6. Sorbitol -white -70% w/w used as vehicle
-miscible with water
-sweet taste
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.

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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 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
• 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
• 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.

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 2. It must be nontoxic, nonsensitizing, adequately soluble, compatible and acceptable
with respect to taste and odor.

Sr. Class Usual


No concentration
(%)
1 ACIDIC 0.2-0.5
Phenol 0.05-0.1
Chlorocresol 0.005-0.01
O-phenyl phenol 0.001-0.2
Alkyl esters of parahydroxybenzoic acid 0.1-0.3
Benzoic acid and its salts 0.5-1.0
Boric acid and its salts 0.05-0.2
Sorbic acid and its salts

2 NEUTRAL 0.5
Chlorobutanol 1.0
Benzyk alcohol 0.2-1.0
B- phenylethyl alcohol
3 MERCURIAL 0.001-0.1
Thimerosal 0.002-0.005
Phenylmercuric acetate and nitrate 0.001-0.02
Nitromersol
4 QUARTERN ARY AMMONIUM 0.004-0.02
COMPOUNDS 0.01-0.02
Benzalkonium chloride
Cetylpyridinium chloride

8. SWEETENING AGENTS:
1. Sucrose
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.

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 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.

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
• - Ethereal - camphoraceous - Musky
• - Floral -Pepperminty -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 - Rosemary
e. Roots
- Glycyrrhiza
f. Barks/Stems
- White pine

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


-Cinnamon
-Wild Cherry Bark
g. Woods
- Quassia
h. Gums
- Gum arabic
- Gum Tragacanth

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 flavour

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, Vanilla

10. Coloring agents

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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 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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


 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:
 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:

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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.
• 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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 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.
• 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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 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

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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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(ρ2 –ρ1) g
18η

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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


 SUSPENSION FORMULATION

1. Aggregated systems
2. dispersed systems
3.Rheologic considerations
4.Formulation Adjuvant
5.Preparative techniques

· 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.

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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 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.

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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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

1. Dilution Test Emulsion can be diluted with onlyUseful for liquid


(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 Observation Comments

2. Dye Test Water soluble solid dye (amaranth) shows color May fail if ionic
only with O/W emulsion, while sudan-III or emulgents are
(Staining) Scarlet red Dyes readily tint a W/O emulsion. present.

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


changed to pink when O/W emulsion is added.
Paper

4. Fluorescence Many oils when exposed to U.V. light Not always


Test fluorescence. applicable

O/W exhibit dot patter.

W/O entire field fluoresces.

5. Direction of A. If emulsion creams are upward the


creaming test emulsion is O/W type.

B. If the emulsion creams are downward it is


W/O type emulsion.

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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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.

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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 Qty for primary emulsion


Oil Water Gum
1. Fixed oils Almond oil 4 2 1
Arachis oil
Castor oil
Cod liver oil
2. Mineral oil Liquid paraffin 3 2 1
3. Volatile oil Turpentine oil 2 2 1
Cinnamon
Peppermint
4. Oleo-resin Male fern Extract 1 2 1

FORMULATION OF EMULSION/ MANUFACTURING OF EMULSION

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• For the formulation of emulsion, both the physical and chemical parameters
to be consider.

• Physical Parameters.
• 1. Heat
• 2.Timing

Chemical parameters (Read lachmann for detail)

• Chemical stability

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


• 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 (%)

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


1 ACIDIC 0.2-0.5
Phenol 0.05-0.1
Chlorocresol 0.005-0.01
O-phenyl phenol 0.001-0.2
Alkyl esters of parahydroxybenzoic acid 0.1-0.3
Benzoic acid and its salts 0.5-1.0
Boric acid and its salts 0.05-0.2
Sorbic acid and its salts
2 NEUTRAL 0.5
Chlorobutanol 1.0
Benzyk alcohol 0.2-1.0
B- phenylethyl alcohol
3 MERCURIAL 0.001-0.1
Thimerosal 0.002-0.005
Phenylmercuric acetate and nitrate 0.001-0.02
Nitromersol
4 QUARTERN ARY AMMONIUM COMPOUNDS 0.004-0.02
Benzalkonium chloride 0.01-0.02
Cetylpyridinium chloride

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

 EVALUATION/STABILITY OF EMULSION
• Creaming
• Flocculation

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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

LIQUID DOSAGE FORMS PREPARED BY: MR. NARESH RAJGOR


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

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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

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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:

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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 it’s 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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• 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 it’s 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 ¼ it’s original volume by boiling during the extraction procedure.
• Then the concentrated extract it filtered and use as such for processed further.

Infusion Decoction
1-Plant Soft structure Hard woody structure
2-Menstrum Cold or hot water Hot water
3-Procedure Infusing the drug with Boiling the drug with menstrum
menstrum
4-time Calculated as soon as water is Calculated as soon as water
added to drug begin to boil
5-adjustment of final volume No adjustment Adjustment required
6-appartus Earthenware pot Ant covered apparatus
7-storage Use within 12 hrs Use fresh

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

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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 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.

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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