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粒径和混合机尺寸对双组份颗粒混合混合性能的影响:DEM 与实验研究。

Influence of particle size and blender size on blending performance of bi-component granular mixing: A DEM and experimental study.

机构信息

Pharmaceutical Development, Daiichi Sankyo Europe GmbH, Pfaffenhofen 85276, Germany; Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., Hiratsuka 2540014, Japan; Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany.

Pharmaceutical Development, Daiichi Sankyo Europe GmbH, Pfaffenhofen 85276, Germany.

出版信息

Eur J Pharm Sci. 2019 Jun 15;134:205-218. doi: 10.1016/j.ejps.2019.04.024. Epub 2019 Apr 26.

DOI:10.1016/j.ejps.2019.04.024
PMID:31034985
Abstract

The effect of particle size enlargement and blender geometry down-scaling on the blend uniformity (BU) was evaluated by Discrete Element Method (DEM) to predict the blending performance of a binary granular mixture. Three 10 kg blending experiments differentiated by the physical properties specifically particle size were performed as reference for DEM simulations. The segregation behavior observed during the diffusion blending was common for all blends, while the sample BU, i.e., standard deviation of active ingredient content % was different among the three blends reflecting segregation due to the particle size differences between the components. Quantitative prediction of the sample BU probability density distribution in reality based on the DEM simulation results was successfully demonstrated. The average root mean square error normalized by the mean of the mean sample BU in the blends was 0.228. Beside the ratio of blender container to particle size, total number of particles in the blender and the number of particles in a sample were confirmed critical for the blending performance. These in-silico experiments through DEM simulations would help in setting a design space with respect to the particle size and in a broader sense with respect to the physical properties in general.

摘要

采用离散元法(DEM)评估粒径增大和混合机几何尺寸缩小对混合均匀性(BU)的影响,以预测二元颗粒混合物的混合性能。进行了三个 10kg 的混合实验,这些实验通过特定的物理性质(特别是粒径)进行区分,作为 DEM 模拟的参考。在扩散混合过程中观察到的分离行为在所有混合物中都很常见,而三个混合物中的样本 BU(即活性成分含量%的标准偏差)不同,这反映了由于组件之间粒径差异导致的分离。成功地证明了基于 DEM 模拟结果对实际样本 BU 概率密度分布的定量预测。在混合物中,样本 BU 的平均均方根误差与平均样本 BU 的平均值之比为 0.228。除了混合机容器与颗粒尺寸的比值外,混合机中的总颗粒数和样品中的颗粒数对于混合性能也至关重要。这些通过 DEM 模拟进行的计算机实验将有助于确定与粒径有关的设计空间,并且更广泛地说,将有助于确定与一般物理性质有关的设计空间。

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