Boehling P, Toschkoff G, Knop K, Kleinebudde P, Just S, Funke A, Rehbaum H, Khinast J G
Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany.
Eur J Pharm Sci. 2016 Jul 30;90:14-24. doi: 10.1016/j.ejps.2015.12.022. Epub 2015 Dec 18.
This work concerns a tablet coating process in an industrial-scale drum coater. We set up a full-scale Design of Simulation Experiment (DoSE) using the Discrete Element Method (DEM) to investigate the influence of various process parameters (the spray rate, the number of nozzles, the rotation rate and the drum load) on the coefficient of inter-tablet coating variation (cv,inter). The coater was filled with up to 290kg of material, which is equivalent to 1,028,369 tablets. To mimic the tablet shape, the glued sphere approach was followed, and each modeled tablet consisted of eight spheres. We simulated the process via the eXtended Particle System (XPS), proving that it is possible to accurately simulate the tablet coating process on the industrial scale. The process time required to reach a uniform tablet coating was extrapolated based on the simulated data and was in good agreement with experimental results. The results are provided at various levels of details, from thorough investigation of the influence that the process parameters have on the cv,inter and the amount of tablets that visit the spray zone during the simulated 90s to the velocity in the spray zone and the spray and bed cycle time. It was found that increasing the number of nozzles and decreasing the spray rate had the highest influence on the cv,inter. Although increasing the drum load and the rotation rate increased the tablet velocity, it did not have a relevant influence on the cv,inter and the process time.
这项工作涉及工业规模鼓式包衣机的片剂包衣过程。我们使用离散元法（DEM）建立了一个全面的模拟实验设计（DoSE），以研究各种工艺参数（喷雾速率、喷嘴数量、转速和料鼓负载）对片剂间包衣变异系数（cv,inter）的影响。包衣机中最多装入290千克物料，相当于1,028,369片片剂。为模拟片剂形状，采用了粘结球体方法，每个建模片剂由八个球体组成。我们通过扩展粒子系统（XPS）对该过程进行了模拟，证明了在工业规模上准确模拟片剂包衣过程是可行的。根据模拟数据外推达到均匀片剂包衣所需的过程时间，其与实验结果吻合良好。结果以各种详细程度呈现，从深入研究工艺参数对cv,inter的影响以及在模拟90秒内进入喷雾区的片剂数量，到喷雾区内的速度以及喷雾和床层循环时间。研究发现，增加喷嘴数量和降低喷雾速率对cv,inter的影响最大。虽然增加料鼓负载和转速会提高片剂速度，但对cv,inter和过程时间没有显著影响。
