期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 552, 期 1-2, 页码 288-300出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2018.09.032
关键词
Continuous manufacturing; Continuous mixing technology; Discrete element method; Cohesive contact model; Residence time distribution; Operating space; Process modeling
资金
- Austrian COMET Program under the Austrian Federal Ministry of Transport, Innovation and Technology (bmvit)
- Austrian Federal Ministry of Economy, Family and Youth (bmwfj)
- State of Styria (Styrian Funding Agency SFG)
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.
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