The production of pharmaceutical tablets is shifting towards continuous manufacturing. Therefore, individual unit operations such as powder blending need to be re-designed. Continuous powder blending has been implemented successfully, but for low-dose formulations this is challenging due to difficulties with continuously dosing small amounts of powder. To overcome such challenges, a semi-continuous mini-blending operation combined with batch-wise dosing can be introduced in a continuous process. The objective of this study is to investigate key factors that affect blending performance of a novel, semi-continuous mini-blending process. A design of experiments is performed, varying both process settings and blend formulations. This reveals that blending performance of the mini-blending process is largely controlled by process settings. These results show that the mini-blender design, with high mixing intensity and short mixing times, supports process intensification of powder blending. The results obtained can be used for Quality by Design-based formulation development for continuous direct compression.

DFE Pharma, Klever Strasse 187, 47568 Goch, Germany

Gericke AG, Althardstrasse 120, CH-8105 Regensdorf, Switzerland

GSK, Park Road, Ware SG12 0DP, United Kingdom

1. Continuous direct compression
2. Direct compression