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 Liquid dosage forms are pourable pharmaceutical

formulations which contain a mixture of
 active drug components and nondrug components
(excipients)
 dissolved or suspended in a suitable solvent or
mixtures of solvents

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 Suitable dosage form for patients who have
difficulty taking tablets or capsules.
 Bioavailability of liquids is more than solids.
 The solution is the only form in which certain
compounds can be obtained.
 Liquid dosage formulations can be made more
pleasant by adding suitable colors, flavors, and
sweeteners.

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 Most of the drugs are known to undergo reactions like
hydrolysis and oxidation.
 Has short shelf life due to low stability.
 Liquids are stored in the containers which create problems
like sorption, leaching, air permeability.
 The bulk and weight of dosage forms are high.
 Liquids are more prone to bacterial contamination.

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 Liquid dosage forms

Polyphasic liquid Monophasic

D.F liquid D.F

Aqueous or
Colloids
Suspensions Emulsions non aqueous
(1µm-1nm)
solutions

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  Defn: Homogeneous mixture (solute and solvent) composed of
only one phase.
Classification:
a) Types :
 Any combination of the three state of matter (S, L, and G)
 Solid in liquid (S/L) and liquid in liquid (L/L) are major
pharmaceutical interest
b) Route of administration
 Otic, ophthalmic, topical, parentral

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Formulation consideration
 Rational:
 Some drugs are inherently unstable
 Special techniques are required to solublize
poorly soluble drugs
 Satisfy the requirements of pharmaceutical
elegance

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1) Solubility
Factors affecting solubility
 Intensity of the forces present in the solute, the solvent
and resultant solute solvent interaction
 Temperature
 Molecular structure
 pH
 Particle size
 Agitation
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Method of Improving solubility
a) Use of solubilizing agents
 Polyoxyethylene
Sorbitan
Fatty acid esters
Sucrose monoesters
 Lanolin
b) Use of co-solvents
 Sorbitol, Glycerin, Propylene glycol
c) Chemical modification of the drug

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a) Raw Materials: b) Excipients

should Comply with  Preservatives

specifications like:  Sweetening agent

 Identity, purity,  Viscosity of control

uniformity and  Flavours

freedom from  Solvents

excessive microbial  Purified water USP

Alcohol, USP (ethanol)
contamination.
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c) Equipments
 Mixing tanks equipped with a means of agitation
 Measuring devices
 Filtration system
 System for bulk material handling, discharging

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 Filling and Packaging
Filling
a) Volumetric filling
 pumping of a liquid at a constant pressure
b) Gravimetric filling
 By the aid of gravitational force
c) Constant level filling
Uses the container as the means for controlling the fill.
The fill amount is varied by adjusting the height to which
the container is filled.
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Suspensions
 A coarse dispersion in which internal phase is
dispersed uniformly throughout the external phase
 The internal phase consisting of insoluble solid
particles having a specific range of size.
 The external phase (suspending medium) is generally
aqueous in some instance, may be an organic or oily
liquid for non oral use.

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Classification of Suspensions
a) Based on route of admin.
 Oral suspension
 Externally applied suspension
 Parenteral suspension
b) Based on Proportion of Solid Particles
 Dilute suspension (2 to10%w/v solid)
 Concentrated suspension (50%w/v solid)

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c) Based on Electro-kinetic Nature of Solid Particles
 Flocculated suspension
 Deflocculated suspension
d) Based on Size of Solid Particles
 Colloidal suspension (< 1 micron)
 Coarse suspension (>1 micron)
 Nano suspension (10 nm)

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Desired Features of Pharmaceutical Suspensions
 Must be easily re-suspended by the use of moderate
amount of shaking.
 It should be easy to pour yet not watery and no grittiness
 It should have pleasing odour, colour and palatability
 Good syringeability
 Should be physically, chemically and microbiologically
stable
 Parenteral/Ophthalmic suspension should be sterilizable
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a) Formulation consideration
Theory of Sedimentation
 Velocity of sedimentation expressed by Stoke’s
equation

 Where,
 Vsed. = sedimentation velocity in cm / sec
d = Diameter of particle

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r = radius of particle
 ρ s= density of disperse phase
 ρ o= density of disperse media
g = acceleration due to gravity
η = viscosity of disperse medium in poise

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Factors Affecting Sedimentation
1) Particle size diameter (d)
Vαd2
2) Density difference between dispersed phase and
dispersion media (ρs - ρo) ,
V α (ρ s - ρo)
3) Viscosity of dispersion medium (η )
V α 1/ ηo

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1.Tank selection
 Material of the tank must not be additive to the product
 The shape and size of equipment must be selected
according to the batch size
 The tanks are usually constructed of polished stainless
steel of different grades
 Adequate clean-up procedures developed.

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2. Mixing
 Simple mixing is essential to increase flow of liquids.
 If the liquid is of high viscosity, high electrical stirrer
may be used.
 Addition of ingredients in proper order have vital
important.
 At high viscosity the chance of air entrapment.

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 Filtration procedure, requires careful evaluation.
 During the pilot run the clarity of the filtrate should be
checked periodically.
 In filtration, filter pads are used which is made up of
asbestos and cellulose.
 Selection of filtration depends on
 The product viscosity
 Volumes
 Rate requirement
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 Filling – important parameter in the transfer of liquids
from tank to tank and into containers.
 New batches should not be started until the previous
batches are completely filled and the tanks are
emptied.

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 It is more important to store the final product in
container until its expiration.
 Most oral liquids are packed in either amber or flint
glass containers with plastic or metal caps.

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 Stability testing
 Sedimentation volume for its ease of re-dispersion
 Particle size change
 Testing PH value of medium
 Microbiological contamination test
 Quantitative content of active substance

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 An emulsion is a dispersion in which the dispersed
phase is composed of small globules of a liquid
distributed throughout a vehicle in which it is immiscible.
 The dispersed liquid is known as the Internal or
Discontinuous phase.
 The dispersion medium is known as the External or
Continuous phase

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Types of emulsion
1) Water in oil (w/o) emulsion
 Water droplets are the internal phase and oil is
external phase
 Preferred for external use
 Emulsifying agents used include wool fat, resin,
beeswax, soaps of divalent and trivalent metals like
Ca, Mg, Zn.

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2) Oil in water (o/w) emulsion
 Oil globules is internal phase and water is external
phase
 Preferred for internal use
 Emulsifying agents used include acacia, Tragacanth,
methylcellulose salt of monovalent bases, Na, K, NH4

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 3) Multiple emulsion
 Oil in water in oil (o/w/o)
 Water in oil in water (w/o/w)
Formulation of emulsion
a) Dry gum method (4:2:1 method)
 4 parts (volumes) of oil
 2 parts of water
 1 parts of gum
 In this method the oil is first triturated with gum and then
water is added
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b) English or wet gum method
 4 parts (volumes of oil)
 2 parts of water
 1 part of gum
 same proportion of oil, water and gum are used as in
dry gum method
 but the order of mixing is different. (gum-water-oil)

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a) Cracking
 Separation of the two layers
Reasons/cause
 Addition of emulsifying agent of opposite type
 Decomposition of emulsifying agent
 Microbial growth
Recommendation
 Add preservatives
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b) Creaming & Sedimentation
 Up ward or downward movement of the dispersed globules
Reasons/causes
 Size of globules
 Viscosity of continuous phase
 Temperature
Recommendation
 Decrease size of globule
 Increase homogenization
 Increase viscosity of continuous phase
 Decrease temperature (keep cool)

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c) Phase inversion
 Change of one type of emulsion to the other type
Reasons/causes
 Change in the phase volume ratio
 Addition of electrolyte
 Changing the emulsifying agent
 Temperature
Recommendation
 Change the emulsifying agent
 Not add/minimize electrolyte/
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Equipment for production of emulsion
 Mechanical Stirrer
 Homogenizer
 Ultrasonifiers
 Filler and packaging

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 Method of determining type of macro-emulsion (O/W & W/O)

a) Phase dilution test

Based on the principle that an emulsion can only be
diluted in a liquid that constitute the continuous phase.
b) Dye solubility test
A colored dye soluble only in one component is added
to the emulsion, if the color spread through out the whole
system, the phase in which the dye is soluble is the
continuous phase.
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C) Conductivity Test
Immerse a pair of electrode connected to the external
electric source. If the external phase is water, a
current pass through the emulsion.

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