Managing API raw material variability during continuous twin-screw wet granulation.

Area of Science:

• Pharmaceutical Manufacturing
• Process Engineering
• Materials Science

Background:

• Raw material variability significantly impacts pharmaceutical manufacturing processes, particularly granule critical quality attributes (CQAs).
• Twin-screw wet granulation is a widely used process, but its robustness against active pharmaceutical ingredient (API) variability requires further investigation.
• Previous work characterized API batch-to-batch variability using principal component analysis (PCA).

Purpose of the Study:

• To investigate the impact of API raw material variability on twin-screw wet granulation.
• To identify critical process parameters and API properties influencing granule CQAs.
• To establish a design space for robust granulation controlling for API variability.

Main Methods:

• Utilized principal component analysis (PCA) results from prior API characterization.
• Employed a D-optimal screening design of experiments with PCA factors and process parameters (screw speed, liquid-to-solid ratio).
• Applied a D-optimal optimization design to determine the process design space and control risk.

Main Results:

• API particle size distribution, density, and agglomeration profile were identified as critical factors for granule CQAs.
• A robust design space was established, demonstrating the ability to achieve desired granule CQAs.
• The process successfully managed API batch-to-batch variability, achieving a 1% risk of failure.

Conclusions:

• Twin-screw wet granulation can be optimized to manage API raw material variability.
• Controlling specific API properties and process parameters ensures consistent granule CQAs.
• This approach enables the production of high-quality granules despite inherent raw material inconsistencies.