Process intensification using a semi-continuous mini-blender to support continuous direct compression processing
Maarten Jaspers, Timo P. Roelofs, Alexandra Lohrmann, Florian Tegel, Muhammad Khalid Maqsood, Yunfei Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff
Abstract
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.