Process intensification using a semi-continuous mini-blender to support continuous direct compression processing
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.
Highlights
Demonstration of a semi-continuous powder mini-blender for process intensification.
Mini-blender design supports continuous direct compression of low drug loads.
Extend of process intensification is impacted by blending regime.
Powder flow and tablet properties are affected by blending process and excipients.
Mixing process intensification allows product optimization to focus on other CQA’s.
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.
2.1. Materials
Anhydrous lactose (SuperTab® 21AN), spray dried lactose (SuperTab® 11SD), agglomerated lactose (SuperTab® 30GR), microcrystalline cellulose (Pharmacel® 102) and croscarmellose sodium (Primellose®) were obtained from DFE Pharma (Goch, Germany). Paracetamol dense powder (referred to as coarse API grade in this manuscript) and fine powder (referred to as fine API grade in this manuscript) were purchased from Mallinckrodt Inc. (Raleigh, NC, USA). Magnesium Stearate was purchased from Sigma Aldrich (St. Louis, MO, USA).
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Maarten Jaspers, Timo P. Roelofs, Alexandra Lohrmann, Florian Tegel, Muhammad Khalid Maqsood, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff, Process intensification using a semi-continuous mini-blender to support continuous direct compression processing, Powder Technology, Volume 428, 2023, 118844, ISSN 0032-5910,
https://doi.org/10.1016/j.powtec.2023.118844.
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