Detailed modeling and process design of an advanced continuous powder mixer.

Autor: Toson P; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria., Siegmann E; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria., Trogrlic M; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria., Kureck H; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria., Khinast J; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria; Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria., Jajcevic D; Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria. Electronic address: dalibor.jajcevic@rcpe.at., Doshi P; Worldwide Research and Development, Pfizer Inc., Groton, CT, USA., Blackwood D; Worldwide Research and Development, Pfizer Inc., Groton, CT, USA., Bonnassieux A; Worldwide Research and Development, Pfizer Inc., Groton, CT, USA., Daugherity PD; Worldwide Research and Development, Pfizer Inc., Groton, CT, USA., Am Ende MT; Worldwide Research and Development, Pfizer Inc., Groton, CT, USA.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2018 Dec 01; Vol. 552 (1-2), pp. 288-300. Date of Electronic Publication: 2018 Sep 27.
DOI: 10.1016/j.ijpharm.2018.09.032
Abstrakt: 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.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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