Solids: Tablets and Capsules
Pilot plant scale up solid dosage forms such as tablets and capsules involve ensuring that formulation performance remains consistent as batch sizes increase. Key considerations include:
1) Blend Uniformity
Importance: Ensures even distribution of active pharmaceutical ingredients (API) and excipients.
Factors: Order of mixing, mixing time, type and scale of equipment.
Scale-Up Impact: Larger batch sizes may alter blending dynamics, requiring equipment adjustments.
2) Granulation
Purpose: Enhances flow properties and compressibility.
Methods: Wet granulation and dry granulation.
Scale-Up Considerations:
Maintain consistent wetness levels in wet granulation.
Adjust equipment design and mixing parameters to preserve granule properties.
3) Compression Properties
Critical Factors: Compressibility, punch speed, compression force, dwell time.
Goals: Achieve desired tablet hardness without defects like capping or lamination.
Scale-Up Impact: Production-scale presses may require parameter adjustments to match lab-scale results.
4) Die Fill
Objective: Ensure each tablet contains the correct dose.
Challenges: Changes in powder flow properties can affect die fill consistency.
Solutions: Optimize flow aids and equipment settings to maintain uniformity.
5) Coating (If Applicable)
Parameters: Spray rate, pan speed, inlet temperature, atomization pressure.
Goals: Achieve uniform and consistent coating for appearance, stability, and drug release.
Scale-Up Impact: Adjust coating equipment settings to maintain consistency.
6) Drying
Importance: Ensures uniform moisture content in granules.
Scale-Up Considerations: Optimize drying time and temperature, especially when transitioning from tray dryers to fluid bed dryers.
7) Capsule Filling
Key Aspects: Consistent fill weight, flow properties, filling speed, equipment design.
Scale-Up Impact: Ensure uniformity through optimized filling machinery and processes.
8) Stability
Focus: Maintain product stability throughout shelf-life.
Scale-Up Considerations: Conduct stability studies to assess ingredient interactions and moisture content.
9) Packaging
Factors: Barrier properties, seal integrity, material compatibility.
Goals: Protect product stability and integrity.
Scale-Up Impact: Select appropriate packaging materials and machinery for large-scale production.
Documentation for Solids
Batch Manufacturing Record (BMR): Detailed process documentation.
Quality Control (QC) Testing: Hardness, friability, dissolution, assay.
Stability Protocols and Reports: Shelf-life studies.
Validation Protocols and Reports: Process consistency and reproducibility.