PROCESS VALIDATION

TABLETS/CAPSULES

GVP (Good Validation Practice)

Integral part of GMP
Commercially sensible pro partition
De risk your business

FORMAL PROCESS VALIDATION

Establish
- Process consistency
- Process reproducibility
Validate
- Only criticle parameters

UNIT OPERATION TO BE VALIDATED

Sifting / Milling
Preparation of granulating agent
Dry mixing & wet granulation
Wet milling
Drying
Dry milling
Blender / Lubricantion
Tablet compression / Capsule filling
Coating
Packing

Sifting / Milling

- Removal of extraneous matter

- Generation of dust
- Dispense & sift or sift & dispense
- Selection & maintenance
- Understand your material
Preparation of granulating agent

- Separate or in situ?
- Understand the chemistry

Preparation of granulating solution

- Solute & solvent ratio

- Dispersing & socking
Temperature
Dispersion technique
Technique

Equipment Design

- Heating / Cooling
- Agitation
- Safety consideration

Dry Mixer

- Need for uniformity of distribution

- Difficulty to predict theoretically
- Possibility of de mixing
- Tituration / sequence of addition
- Sampling for testing
- Safety consideration

Sampling for testing blend uniformity

- Time lapsed
- Sample from different location
- Sampling device
- Quantity sampled
- What to test for?
- Critical for low dosage form half tablet?
- Multi component system
Wet granulation

- Rate of addition of granulating agent

- Mixer controls
Better & cheaper speed
Temperature of mars
Solvent vapors
Inert gassing?
- Granulation and instrumentation

Wet milling

- Prerequisite for drying

- Choice of equipment

Drying

- Type of equipment
- FBD control
Analyze quality & control
filters & heaters
local per charge
temperature time relationship
distributors plate / sieve
(Heat) moisture content / LOD
- Drying control
Measurement of moisture, RH
Over / under drying
FBD bags washing / drying and storage
- Safety consideration
Dust exposure
Exit filters

Dry milling

- Type of equipment
Screens used
No. of blends
Direction of rotation
- Influence of heat on granular
- Storage of milled granules
Blending & lubrication

- Blender design & loading capacity

- Pre treatment of lubricants
- Single granules / separate granule
- Blender loading dust generation
- Speed & duration over /under mixing
- Sampling & testing of granules
- Storage of lubricated granules

Tablet compression

- Tooling & maintenance

- Granule feeding systems
- Operational controls
Appearance
Dimensional consistency
Other physical characteristics (friability / hardness)
- Sampling frequency
- Testing
- Storage of bulk tablet

Tablet coating

- Coating mixtures
Preparation & storage
- Process variable & controls
Speed of pan
Spray quantity
Drying test
Weight gain
Environmental control
- Storage bulk

Capsule filling

- Storage of empty HG capsule

Shell moisture
Localized hot spots
Storage during operation
- Storage after filling