Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Materials Science

Background:

• Continuous powder feeding is essential for consistent solid dosage form manufacturing.
• Poorly flowing active pharmaceutical ingredients (APIs) and their batch variability pose significant challenges to twin-screw feeding capacity and process consistency.

Purpose of the Study:

• To investigate and improve twin-screw feeding of pharmaceutical blends containing a poorly flowing API with high batch-to-batch variability.
• To evaluate formulation modifications aimed at enhancing blend flowability and mitigating API variability effects on feeding performance.

Main Methods:

• Extensive material characterization of reformulated blends.
• Continuous twin-screw feeding evaluation tests.
• Assessment of formulation changes on blend properties and feeding behavior.

Main Results:

• Transferring the glidant to the intra-granular phase significantly improved blend flowability.
• Sufficient feeding capacity was achieved, and the impact of API batch variability on twin-screw feeding was mitigated.
• Key material attributes critical for feeding were identified: bulk density, mass charge, and powder cohesiveness.

Conclusions:

• Reformulation strategies, specifically glidant transfer, can successfully address challenges in continuous powder feeding of difficult-to-handle APIs.
• Optimized formulations ensure consistent feeding performance and mitigate raw material variability, crucial for robust continuous manufacturing.
• Understanding critical material attributes is key to successful process development in pharmaceutical powder handling.