Pharmaceutical excipients properties and screw feeder performance in continuous processing lines: a Quality by Design (QbD) approach

Abstract

Screw feeder performance is a critical aspect in continuous manufacturing processes. Pharmaceutical excipients, such as mannitol, microcrystalline cellulose, lactose monohydrate, and anhydrous dibasic calcium phosphate can present problems in ensuring a continuous stable feed rate due to their sub-optimal flow properties. In alignment with Quality by Design (QbD) goals, the aim of this work was to identify and explain critical sources of variability of some powder excipients delivery by screw feeding, in particular to continuous processing lines. Pharmaceutical excipients with a wide range of material properties were selected, and the impact of their flow and density properties on screw feeder performance was investigated. The analysis of the powder conveying by the screws was performed at different hopper fills and different screw speeds. A multivariable model involving bulk density (CBD) and parameters from FT4 dynamic downwards testing (SI) and dynamic upwards testing (SE) explained 95.7% of excipients feed rates (p < .001). The study gathers valuable information about the screw feeder performance and input materials properties that can help process understanding and QbD-based development of solid dosage forms in continuous processing lines.

Keywords:

• Pharmaceutical excipients
• solid dosage
• materials properties
• powder flow
• screw feeder
• continuous manufacturing
• Quality by Design

Acknowledgments

The authors would like to acknowledge the contribution to this paper from Dr David Armitage for writing the data collection program (Gravy-Bisto) and his helpful teachings; the undergraduate students Pedro Franco and Victor Lucena for helping with the data collection; and GSK Materials Science group lead by Martine McCormick for technical help. The authors would also to thank Prasanna Kulkarni and Richard Elkes for their helpful comments.

Disclosure statement

No potential conflict of interest was reported by the authors.