AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
Int J Pharm. 2013 Dec 15;458(1):218-23. doi: 10.1016/j.ijpharm.2013.09.016. Epub 2013 Sep 25.
The major aims of this work were to study the effect of the molecular weight (Mw) of ethyl cellulose (EC) on the drug release profile from metoprolol succinate pellets coated with films comprising EC and hydroxypropyl cellulose (HPC) with a weight ratio of 70:30, and to understand the mechanisms behind the different release profiles. A broad range of Mws was used, and the kinetics of drug release and HPC leaching followed. The higher the Mw of EC, the slower the HPC leaching and the drug release processes. Drug release occurred by diffusion through the pores created in the coating by the HPC leaching. A novel method was used to explain the differences in the release profiles: the effective diffusion coefficient (De) of the drug in the coating film was determined using a mechanistic model and compared to the amount of HPC leached. A linear dependence was found between De and the amount of HPC leached and, importantly, the value of the proportionality constant decreased with increasing Mw of EC. This suggests that the Mw of EC affects the drug release profile by affecting the phase separated microstructure of the coating and the hindrance it imparts to drug diffusion.
本工作的主要目的是研究乙基纤维素（EC）的分子量（Mw）对包衣以乙基纤维素（EC）和羟丙基纤维素（HPC）（重量比为 70:30）的酒石酸美托洛尔控释微丸的药物释放特性的影响，并了解不同释放特性背后的机制。使用了广泛的 Mw 范围，并跟踪了药物释放和 HPC 溶出的动力学。EC 的 Mw 越高，HPC 溶出和药物释放过程越慢。药物通过 HPC 溶出在涂层中形成的孔扩散释放。采用一种新方法来解释释放特性的差异：使用机械模型确定涂层中药物的有效扩散系数（De），并将其与 HPC 的溶出量进行比较。发现 De 与 HPC 的溶出量之间存在线性关系，重要的是，比例常数的值随 EC 的 Mw 的增加而降低。这表明，EC 的 Mw 通过影响涂层的相分离微观结构及其对药物扩散的阻碍作用来影响药物释放特性。
