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Improvement of a pharmaceutical powder mixing process in a tote blender via DEM simulations

By Benedict Benque1; Luca Orefice1; Thomas Forgber1; Matthias Habeler2; Beate Schmid2; Johan Remmelgas1; Johannes Khinast3

1. Research Center Pharmaceutical Engineering GmbH 2. Sandoz GmbH 3. Research Center Pharmaceutical Engineering GmbH, Institute of Process and Particle Engineering, TU Graz

Published on CMKC


An industrial-scale pharmaceutical powder blending process was studied via discrete element method (DEM) simulations. A DEM model of two active pharmaceutical ingredient (API) components and a combined excipient component was calibrated by matching the simulated response in a dynamic angle of repose tester to the experimentally observed response. A simulation of the 25-minute bin blending process predicted inhomogeneous API distributions along the rotation axis of the blending container. These concentration differences were confirmed experimentally in a production-scale mixing trial using high-performance liquid chromatography analysis of samples from various locations in the bin. Several strategies to improve the blend homogeneity were then studied using DEM simulations. Reversing the direction of rotation of the blender every minute was found to negligibly improve the blending performance. Introducing a baffle into the lid at a 45° angle to the rotation axis sped up the axial mixing and resulted in a better final blend uniformity. Alternatively, rotating the blending container 90° around the vertical axis five minutes prior to the process end was predicted to reduce axial segregation tendencies.


International Journal of Pharmaceutics



Type of publication

Peer-reviewed journal


  • Research Center Pharmaceutical Engineering GmbH
  • Sandoz GmbH
  • Institute of Process and Particle Engineering, TU Graz

Article Classification

Research article

Classification Areas

  • API
  • Oral Solid Dosage