Simulation of a tablet coating process at different scales using DEM

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• 作者：P. Boehling^a ; G. Toschkoff^a ; S. Just^b ; K. Knop^b ; P. Kleinebudde^b ; A. Funke^d ; H. Rehbaum^e ; P. Rajniak^a ; J.G. Khinast^a ; ^c ; ^{khinast@tugraz.at" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Coating ; Scale-up ; Simulation ; Multi-scale modeling ; Discrete Element Method
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：10 October 2016
• 年：2016
• 卷：93
• 期：Complete
• 页码：74-83
• 全文大小：2373 K

文摘

Spray coating of tablets is an important unit operation in the pharmaceutical industry and is mainly used for modified release, enteric protection, better appearance and brand recognition. It can also be used to apply an additional active pharmaceutical ingredient to the tablet core. Scale-up of such a process is an important step in commercialization. However, scale-up is not trivial and frequently, at manufacturing scales the required coating quality cannot be reached. Thus, we propose a method where laboratory experiments are carried out, yet scale-up is done via computational methods, i.e., by extrapolating results to larger scales.

In the recent years, the Discrete Element Method (DEM) has widely been used to simulate tablet behavior in a laboratory scale drum coater. Due the increasing computational power and more sophisticated DEM algorithms, it has become possible to simulate millions of particles on regular PCs and model industrial scale tablet coating devices. In this work, simulations were performed on the laboratory, pilot and industrial scales and DEM was used to study how different scale-up rules influence the bed behavior on larger scales. The material parameters of the tablets were measured in the laboratory and a glued sphere approach was applied to model the tablet shape.

The results include a vast amount of qualitative and quantitative data at the different scales. In conclusion, the evolution of the inter-tablet coating variation for the different scales and process parameters is presented. The results suggest that keeping the Froude number constant during the scale up process leads to faster processes as the cycle time is shorter and the spray residence time is more uniform when compared to keeping the circumferential velocity constant.