Detailed modeling and process design of an advanced continuous powder mixer

Peter Toson, Eva Siegmann, Martina Trogrlic, Hermann Kureck, Johannes Khinast, Dalibor Jajcevic, Pankaj Doshi, Daniel Blackwood, Alexandre Bonnassieux, Patrick D. Daugherity, Mary T. am Ende

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A vertical in-line continuous powder mixing device (CMT – Continuous Mixing Technology) has been modelled with the discrete element method (DEM) utilizing a calibrated cohesive contact model. The vertical design of the mixing device allows independent control of mean residence time (MRT) and shear rate. The hold-up mass and outlet flow are controlled by an exit valve, located at the bottom of the in-line mixer. A virtual design of experiments (DoE) of DEM simulations has been performed and parameters such as particle velocities, powder bed shape, residence time distribution (RTD), travel distance, and mixing quality are evaluated for the complete operating space. The RTD of the DEM model has been validated with tracer experiments. The resulting RTD has been fitted with an analytical form (generalized cascade of n continuous stirred tank reactors) and utilized to study the downstream response of the continuous mixing device to upstream fluctuations in the inlet material stream. The results indicate a high mixing quality and good filtering properties across the operating space. However, the combination of low hold-up mass and high impeller speeds leads to a reduced filtering capability and wider exit valve openings, indicating a less desirable operating point.

Original languageEnglish
Pages (from-to)288-300
Number of pages13
JournalInternational Journal of Pharmaceutics
Volume552
Issue number1-2
DOIs
Publication statusPublished - 1 Dec 2018

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Powders
Equipment Design
Equipment and Supplies
Technology

Keywords

  • Cohesive contact model
  • Continuous manufacturing
  • Continuous mixing technology
  • Discrete element method
  • Operating space
  • Process modeling
  • Residence time distribution

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Detailed modeling and process design of an advanced continuous powder mixer. / Toson, Peter; Siegmann, Eva; Trogrlic, Martina; Kureck, Hermann; Khinast, Johannes; Jajcevic, Dalibor; Doshi, Pankaj; Blackwood, Daniel; Bonnassieux, Alexandre; Daugherity, Patrick D.; am Ende, Mary T.

In: International Journal of Pharmaceutics, Vol. 552, No. 1-2, 01.12.2018, p. 288-300.

Research output: Contribution to journalArticleResearchpeer-review

Toson, Peter ; Siegmann, Eva ; Trogrlic, Martina ; Kureck, Hermann ; Khinast, Johannes ; Jajcevic, Dalibor ; Doshi, Pankaj ; Blackwood, Daniel ; Bonnassieux, Alexandre ; Daugherity, Patrick D. ; am Ende, Mary T. / Detailed modeling and process design of an advanced continuous powder mixer. In: International Journal of Pharmaceutics. 2018 ; Vol. 552, No. 1-2. pp. 288-300.
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