PROCESS VALIDATION

OF LIQUID ORALS

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 WHAT ARE ORAL LIQUIDS?

Oral Liquids are homogeneous liquid

preparations, usually consisting of a solution, an
emulsion or a suspension of one or more active
ingredients in a suitable vehicle.

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CLASSIFICATION OF LIQUID ORALS

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Manufacturing of Monophasic liquids

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 Manufacturing of Biphasic liquids:
WATER
WATER
SURFACTANTS
SURFACTANTS

OTHER
OTHER PRESERVATIVES
PRESERVATIVES
HELPING
HELPING CONTINUOUS
CONTINUOUS DISPERSE PHASE
AGENTS
AGENTS PHASE
PHASE

FOR
FORSUSPENSION
SUSPENSION FOR
FOREMULSION
EMULSION

MIXING
MIXING
GRINDING OF DISSOLVED
DRUG & DRUG IN OIL
OTHER SOLIDS
AQUEOUS
AQUEOUSSOLUTION
SOLUTION
DRUG
DRUGSOLUTION
SOLUTION
MILLED
MILLEDDRUG
DRUG IN
INOIL
OIL
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 Continuous
Continuous
phase
phase

Disperse
Disperse PRE
PRE––MIX
MIX
phase
phase OR
OR
CRUDE
CRUDEDISPERSION
DISPERSION

OTHER ADDITIVES
(FLAVOURS,
pH ADJUSTMENT COLOURING AGENT)

VOLUME ADJUSTMENT
HOMOGENIZE

FINE
FINEDISPERSE
DISPERSEDELIVERY
DELIVERYSYSTEM
SYSTEM

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 Process Variables
Process Equipment Process Properties Monitoring
variables affected by output
variables
Mixing Kettle & Tank Capacity of unit, Appearance of Potency,
of fitted with Shape & position liquid, Appearance,
agitator
liquid of agitation system, Viscosity of liquid. pH,
Order of addition, Viscosity,
Rate of addition, Specific
gravity.
Fill volume,
Mixing speed of
agitator,
Temperature of
liquid,
Mixing time.

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 Process Equipment Process Properties Monitoring
variables affected Output
by
variables
Mixing & Blade mixers Capacity of unit, Particle size Potency,
blending of & tumblers. Mixing speed of of solids,
solids unit, Particle size
Blending analysis,
Shape of unit, uniformity.
position of mixing Content
element within unit, uniformity of
active
Product load. component.

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Process Equipment Process variables Properties Monitorin
affected g output
by
variables
Dispersing Homogenizer, Bore opening/ Particle size Potency,
Colloid mill, clearance of rotor & of solids,
ultrasonic stator, Particle size
device/ Pressure, Viscosity of Distribution,
rotor speed, liquid.
Power consumption, Viscosity,
Feed rate,
Temperature, Specific
Dispersion time, gravity.
Order of mixing.

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Process validation concerns to following
operations:

• Raw material validation

• Monitoring outputs
• Filling and packaging validation

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Raw material validation:

It includes mainly following tests

Particle size and size distribution
Particle shape or morphology
Microbial count
Rheology of solvent or vehicle
PH of the solvent or vehicle

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Monitoring outputs
Some outputs to be monitored are as under:

• Appearance
• pH
• Viscosity
• Specific gravity
• Microbial count
• Content uniformity
• Dissolution testing
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 Appearance of the final product indicates the signs of
instability and degradation.
For e.g. settling of solid particles in case of suspension and
turbidity in case of emulsion.
Time for mixing or agitation and temperature of process
can effect the appearance greatly.
 PH of aqueous oral formulations should be taken at a
given temperature and only after equilibrium has been
reached in order to minimize the PH drift.
 Viscosity affects the settling rate of suspended particles in
suspension and coalescence of globules of internal phase
in emulsions and also in case of oral solutions it affects the
overall appearance of the final product so it must be
measured and validated properly.

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 Specific gravity: A decrease in specific gravity of the
product like suspensions indicates the presence of air
within the structure of the formulation.
 Microbial count for the final product is essential to
validate because by performing microbial count we can
select the preservative for the final product storage.
There are specifications for each liquid oral product for
the bioburden content.
 Content uniformity affects the dose uniformity in case of
multidose formulations and also affects the homogeneity
of the drug within solvent system.
 Dissolution testing: no official method for dissolution
testing of dispersed system

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Test parameters for suspension

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Test parameters for Emulsions

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 Test parameters for emulsion and suspension
Test parameter Suspension Emulsion
Appearance yes yes
Specific gravity yes yes

Viscosity yes yes

PH yes yes

Content uniformity yes yes

Sedimentation yes No

Resuspendability yes No

Particle size yes yes

Release rate yes yes

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Filling and packaging operation validation:

Tests performed:
• Leakage test for filled bottle
• Cap sealing test
• Fill volume determination
• Water vapour permeability test

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 Thank You
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