process validation of liquid orals (pharmaceutical process validation)
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PROCESS VALIDATIONOF LIQUID ORALS
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.
CLASSIFICATION OF LIQUID ORALS
Manufacturing of Monophasic liquids
AQUEOUS SOLUTIONAQUEOUS SOLUTION
FOR SUSPENSIONFOR SUSPENSION FOR EMULSIONFOR EMULSION
DRUG SOLUTIONIN OIL
DRUG SOLUTIONIN OILMILLED DRUGMILLED DRUG
GRINDING OFDRUG &OTHER SOLIDS
DISSOLVED DRUG IN OIL
Manufacturing of Biphasic liquids:
PRE – MIXOR
PRE – MIXOR
FINE DISPERSE DELIVERY SYSTEMFINE DISPERSE DELIVERY SYSTEM
OTHER ADDITIVES(FLAVOURS, COLOURING AGENT)
Process VariablesProcess Equipment Process
variables Properties affected by variables
Kettle & Tank fitted with agitator
Capacity of unit,
Shape & position
of agitation system,
Order of addition,
Rate of addition,
Mixing speed of agitator,
Temperature of liquid,
Appearance of liquid, Viscosity of liquid.
Viscosity, Specific gravity.
Process Equipment Process variables
Mixing & blending of solids
Blade mixers & tumblers.
Capacity of unit, Mixing speed of unit,
Shape of unit,
position of mixing element within unit,
Particle size of solids,
Particle size analysis,
Content uniformity of active component.
Process Equipment Process variables Properties affected
Dispersing Homogenizer, Colloid mill, ultrasonic device/
clearance of rotor & stator,
Order of mixing.
Particle size of solids,
Viscosity of liquid.
Process validation concerns to following operations:
• Raw material validation• Monitoring outputs• Filling and packaging validation
Raw material validation:
It includes mainly following testsParticle size and size distributionParticle shape or morphologyMicrobial countRheology of solvent or vehiclePH of the solvent or vehicle
Some outputs to be monitored are as under:
• Appearance• pH• Viscosity• Specific gravity• Microbial count• Content uniformity• Dissolution testing
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.
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
Test parameters for suspension
Test parameters for Emulsions
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 yes17
Test parameters for emulsion and suspension
Filling and packaging operation validation:
Tests performed:• Leakage test for filled bottle • Cap sealing test• Fill volume determination• Water vapour permeability test
Thank YouSarika Kadam