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使用离散元法对推拉式渗透泵控释片的药物释放进行模拟。

Modelling the controlled drug release of push-pull osmotic pump tablets using DEM.

机构信息

School of Chemistry and Chemical Engineering, University of Surrey, Guildford, UK.

School of Chemistry and Chemical Engineering, University of Surrey, Guildford, UK; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Int J Pharm. 2024 Jul 20;660:124316. doi: 10.1016/j.ijpharm.2024.124316. Epub 2024 Jun 9.

Abstract

The push-pull osmotic pump tablet is a promising drug delivery approach, offering advantages over traditional dosage forms in achieving consistent and predictable drug release rates. In the current study, the drug release process of push-pull osmotic pump tablets is modelled for the first time using the discrete element method (DEM) incorporated with a microscopic diffusion-induced swelling model. The effects of dosage and formulation design, such as delivery orifice size, drug-to-polymer ratio, tablet surface curvature, friction between particles and cohesion of polymer particles, on the drug release performance are systematically analysed. Numerical results reveal that an enlarged delivery orifice significantly increases both the total drug release and the drug release rate. Moreover, the larger the swellable particle component in the tablet, the higher the drug release rate. Furthermore, the tablet surface curvature is found to affect the drug release profile, i.e. the final drug release percentage increases with the increasing tablet surface curvature. It is also found that the drug release rate could be controlled by adjusting the inter-particle friction and the cohesion of polymer particles in the formulation. This DEM study offers valuable insights into the mechanisms governing drug release in push-pull osmotic pump tablets.

摘要

推挽渗透泵片是一种很有前途的药物传递方法,与传统剂型相比,它在实现一致和可预测的药物释放速率方面具有优势。在目前的研究中,首次使用离散元法(DEM)结合微观扩散诱导溶胀模型对推挽渗透泵片的药物释放过程进行了建模。系统分析了剂量和配方设计(如给药孔尺寸、药物-聚合物比、片剂表面曲率、颗粒间摩擦和聚合物颗粒内聚)对药物释放性能的影响。数值结果表明,增大给药孔显著增加了总药物释放量和药物释放速率。此外,片剂中可溶胀颗粒成分越大,药物释放速率越高。此外,还发现片剂表面曲率会影响药物释放曲线,即随着片剂表面曲率的增加,最终药物释放百分比增加。还发现可以通过调整配方中颗粒间的摩擦和聚合物颗粒的内聚来控制药物释放速率。这项 DEM 研究为推挽渗透泵片药物释放的机制提供了有价值的见解。

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