Lao Luciana Lisa, Venkatraman Subbu S, Peppas Nicholas A
School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Eur J Pharm Biopharm. 2008 Nov;70(3):796-803. doi: 10.1016/j.ejpb.2008.05.024. Epub 2008 Jun 6.
Numerous mathematical models that predict drug release from degradable systems have been reported. Most of these models cater only to single step, diffusion-controlled release while a few attempt to describe bi-phasic release. All these models, however, are only applicable to drug release from single (unblended) degradable polymer systems. In this paper, we propose and test novel models for drug (notably paclitaxel) release from films made of neat poly (epsilon-caprolactone) PCL, neat poly (dl-lactide-co-glycolide) PLGA and their blends. The model developed for neat PCL consists of two terms: initial burst and diffusional release. On the other hand, a more complex model proposed for tri-phasic release from neat PLGA consists of burst release, degradative (relaxation-induced) drug dissolution release and diffusional release. Finally, this very first model to predict release from blend of PLGA and PCL was developed based on a heuristic approach. Drug distribution between PCL-rich and PLGA-rich phases is dictated by partition coefficient, and the overall fraction of drug release is a summation of drug released from the two phases. The proposed models exhibited good prediction of the experimental data.
已经报道了许多预测药物从可降解系统中释放的数学模型。这些模型大多仅适用于单步、扩散控制释放，少数尝试描述双相释放。然而，所有这些模型仅适用于从单一（未混合）可降解聚合物系统中释放药物。在本文中，我们提出并测试了用于从纯聚（ε-己内酯）PCL、纯聚（丙交酯-共-乙交酯）PLGA及其混合物制成的薄膜中释放药物（特别是紫杉醇）的新模型。为纯PCL开发的模型由两个项组成：初始突释和扩散释放。另一方面，为纯PLGA的三相释放提出的更复杂模型包括突释、降解（松弛诱导）药物溶解释放和扩散释放。最后，基于启发式方法开发了第一个预测PLGA和PCL混合物释放的模型。PCL富集相和PLGA富集相之间的药物分布由分配系数决定，药物释放的总分数是两相释放药物的总和。所提出的模型对实验数据表现出良好的预测能力。
