Comparisons of intra-tablet coating variability using DEM simulations, asymptotic limit models, and experiments
Comparisons of intra-tablet coating variability using DEM simulations, asymptotic limit models, and experiments
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DOI：
10.1016/j.ces.2015.03.013
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发表时间：
2015-07-28
影响因子：
4.7
通讯作者：
Zeitler, J. Axel
中科院分区：
文献类型：
--
作者：
Freireich, Ben;Kumar, Rahul;Zeitler, J. Axel
离散元法（DEM）计算机模拟用于研究片内包衣厚度的变化。提出了两种新的后处理算法。第一种算法使用基于图像的方法来跟踪每个片剂表面上的小面积面板的模拟喷雾的曝光，使得片剂表面上的喷雾曝光时间的分布可以直接从DEM数据确定。第二种算法预测片剂内包衣均匀度的渐近极限。这第二种算法包括片剂的方向和阴影的影响时，考虑暴露于喷雾，平均超过许多tablets.DEM模拟产生的第一个直接证据表明，非球形片剂接近渐近内片剂包衣变异值。使用新的渐近预测模型预测的渐近极限。通常，片剂帽的包衣比片剂带厚。此外，具有更细长形状的片剂倾向于在带的较小曲率半径部分上具有较少的包衣。在这个新的渐近建模方法中特别重要的是包括阴影效应。当不包括阴影且仅考虑片剂方向时，预测过度预测了渐近片内包衣变异性值，并且还改变了不同片剂形状的渐近值的观察到的秩次。使用新算法的渐近片剂内包衣变异性值与片剂球形度相关性相当好，球形度的增加改善了包衣均匀性。本文还首次尝试直接比较实验和模拟的包衣厚度分布。渐近涂层厚度的预测比较以及定性太赫兹厚度测量片剂从涂层实验。不幸的是，由于实验取样的片剂数量有限，喷雾区面积和通量分布存在差异，因此只能进行定性比较。然而，实验中的药片显示出与模拟中发现的相似的特征。(C)2015作者爱思唯尔有限公司出版
Discrete element method (DEM) computer simulations are used to investigate intra-tablet coating thickness variability. Two new post-processing algorithms are presented. The first algorithm uses an image-based method to track the exposure to a simulated spray of small area panels on each tablet's surface so that the distribution of spray exposure times over the tablet's surface can be determined directly from DEM data. The second algorithm predicts the asymptotic limit of intra-tablet coating uniformity. This second algorithm includes the influence of tablet orientation and shadowing when considering exposure to the spray, averaged over many tablets.The DEM simulations produce the first direct evidence that non-spherical tablets approach asymptotic intra-tablet coating variability values. The asymptotic limits are predicted well using the new asymptotic prediction model. In general, tablet caps have thicker coatings than tablet bands. Moreover, tablets that have a more elongated shape tend to have less coating on the smaller radius of curvature portions of the bands. Of particular importance in this new asymptotic modeling approach is the inclusion of shadowing effects. When shadowing is not included and only tablet orientation is considered, the predictions over-predict the asymptotic intra-tablet coating variability values and also change the observed rank order of the asymptotic values for different tablet shapes. The asymptotic intra-tablet coating variability values using the new algorithm correlate reasonably well with tablet sphericity, with increasing sphericity improving coating uniformity.This paper also presents the first attempt to directly compare experimental and simulated coating thickness distributions. The asymptotic coating thickness predictions compare well qualitatively with terahertz thickness measurements made on tablets from coating experiments. Unfortunately, only qualitative comparisons could be made due to the limited number of tablets sampled experimentally and differences in spray zone areas and flux distributions. The tablets in the experiments, however, displayed similar features as those found in the simulations. (C) 2015 The Authors. Published by Elsevier Ltd.