DEM simulation of drug release from structurally heterogeneous swelling tablets

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• 作者：James A. Kimber ; Sergei G. Kazarian ; Franti?ek ?t¨§p¨¢nek
• 关键词：DEM ; Tablet dissolution ; Mathematical modelling ; Drug release
• 刊名：Powder Technology
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：248
• 期：Complete
• 页码：68-76
• 全文大小：1936 K

文摘

The Discrete Element Method (DEM) was used to generate an unstructured mesh over which mass transfer equations were solved. This has been applied to model swelling and drug release from pharmaceutical tablets and is useful for studying in vitro-in vivo correlation (IVIVC) and virtual formulation development. Parametric studies were conducted into the effect of tablet shape and aspect ratio, polymer properties and shell thickness, and boundary conditions around the tablet on drug release time (t₉₀), the shape of the release curve and tablet evolution. The first study showed that drug release from tablets containing the same mass of polymer and drug but having different shapes and aspect ratios was only dependent on aspect ratio and not tablet shape. Investigations into polymer properties and coating thickness showed that drug release is fastest for moderately swelling polymers and that similar t₉₀ can be obtained for different combinations of parameters. The final study into different boundary conditions found that for highly soluble drugs, the polymer was the rate limiting step for drug release but in other cases, release was limited by the low permeability of the boundary. The increase in bulk volume also slowed drug release and demonstrated that both permeability and bulk volume couple to influence drug release.