Exploring pharmaceutical powder behavior in commercial-scale bin blending: A DEM simulation study

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-10-26 DOI:10.1016/j.ejps.2024.106950
F. Mostafaei , B. Benque , P. Doshi , M.T. Santangelo , H.G. Lee , D. Gomes Lopes , M. Schaefer , J.G. Khinast , D. Jajcevic
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Abstract

Bin blending is one of the main steps in pharmaceutical production processes. Commercial-scale production of expensive products typically does not allow to perform a large number of experiments in order to optimize the process. Alternatively, Discrete Element Method (DEM) simulations can be used to evaluate the powder behavior (flow and blending pattern) during blending, identify the risks (e.g., segregation), and provide solutions to mitigate them. In this work, DEM simulations are used to investigate the blending of two granulated powders in commercial-scale cone and cylindrical (hoop) blenders. The DEM contact model parameters were calibrated based on the experimental compression and ring shear tests for both granulated powders to mimic the bulk powder behavior in the simulations. The model's output was compared to the experiments in one of the blending cases. The blending efficiency in the cone blenders was evaluated considering the fill levels, the presence of baffles, the rotating directions, the filling order, and the bin sizes. Furthermore, for the hoop blenders, the effects of blender's angle, rotation speed, and filling order were addressed. The main findings of the work were that, in cone blenders, the blending can be improved by introducing baffles and changing in the rotational direction frequently. In hoop blenders, blending can be improved by increasing the inclination angle from the horizontal plane and the rotational speed.

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探索商业规模料仓混合中的药粉行为:DEM 模拟研究
配料混合是药品生产过程中的主要步骤之一。昂贵产品的商业规模生产通常无法进行大量实验来优化工艺。另外,离散元素法(DEM)模拟可用于评估混合过程中的粉末行为(流动和混合模式),识别风险(如偏析),并提供解决方案以降低风险。在这项工作中,DEM 模拟用于研究两种颗粒粉末在商业规模的锥形和圆柱形(环形)混合机中的混合情况。DEM 接触模型参数是根据两种粒状粉末的实验压缩和环剪试验校准的,以便在模拟中模拟散装粉末的行为。模型的输出结果与其中一种混合情况下的实验结果进行了比较。考虑到填充水平、挡板的存在、旋转方向、填充顺序和料仓尺寸,对锥形混合器的混合效率进行了评估。此外,对于环形混合器,还研究了混合器角度、旋转速度和填充顺序的影响。研究的主要发现是,在锥形搅拌机中,通过引入挡板和频繁改变旋转方向可以改善搅拌效果。在环形搅拌机中,可通过增加与水平面的倾斜角度和转速来改善搅拌效果。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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