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活性片剂包衣过程的建模

Modeling of an Active Tablet Coating Process.

作者信息

Toschkoff Gregor, Just Sarah, Knop Klaus, Kleinebudde Peter, Funke Adrian, Djuric Dejan, Scharrer Georg, Khinast Johannes G

机构信息

Research Center Pharmaceutical Engineering GmbH, Graz, Austria.

Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany.

出版信息

J Pharm Sci. 2015 Dec;104(12):4082-4092. doi: 10.1002/jps.24621. Epub 2015 Sep 7.

Abstract

Tablet coating is a common unit operation in the pharmaceutical industry, during which a coating layer is applied to tablet cores. The coating uniformity of tablets in a batch is especially critical for active coating, that is, coating that contains an active pharmaceutical ingredient. In recent years, discrete element method (DEM) simulations became increasingly common for investigating tablet coating. In this work, DEM was applied to model an active coating process as closely as possible, using measured model parameters and non-spherical particles. We studied how operational conditions (rotation speed, fill level, number of nozzles, and spray rate) influence the coating uniformity. To this end, simulation runs were planned and interpreted according to a statistical design of (simulation) experiments. Our general goal was to achieve a deeper understanding of the process in terms of residence times and dimensionless scaling laws. With that regard, the results were interpreted in light of analytical models. The results were presented at various detail levels, ranging from an overview of all variations to in-depth considerations. It was determined that the biggest uniformity improvement in a realistic setting was achieved by increasing the number of spray nozzles, followed by increasing the rotation speed and decreasing the fill level.

摘要

片剂包衣是制药行业中一种常见的单元操作,在此过程中,包衣层被施加到片芯上。对于活性包衣(即含有活性药物成分的包衣)而言,一批片剂的包衣均匀性尤为关键。近年来,离散单元法(DEM)模拟在研究片剂包衣方面变得越来越普遍。在这项工作中,利用测量得到的模型参数和非球形颗粒,应用离散单元法尽可能逼真地模拟活性包衣过程。我们研究了操作条件(转速、填充水平、喷嘴数量和喷雾速率)如何影响包衣均匀性。为此,根据(模拟)实验的统计设计来规划和解读模拟运行。我们的总体目标是从停留时间和无量纲缩放定律的角度更深入地理解该过程。就此而言,根据解析模型对结果进行了解读。结果以各种详细程度呈现,从所有变化的概述到深入的考量。结果表明,在实际情况下,通过增加喷嘴数量能实现最大程度的均匀性改善,其次是提高转速和降低填充水平。

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