Department of Biomedical Engineering, Yale University, 55 Prospect St., New Haven, CT 06511, USA.
J Control Release. 2010 Mar 19;142(3):474-82. doi: 10.1016/j.jconrel.2009.11.021. Epub 2009 Dec 1.
The TAXUS Express coronary artery stent delivers a sustained dose of a hydrophobic drug (paclitaxel) from a hydrophobic polymer coating (poly(styrene-isobutylene-styrene), SIBS). It is known that particles of concentrated drug are dispersed throughout the polymer coating, however, the mechanism by which drug exits the polymer matrix is not fully characterized. In this work, mathematical models were applied to in vitro controlled release data obtained from 8.8, 25 and 35% loadings of drug in polymer. Models that accounted for release by different mechanisms were tested. It was observed that Fickian diffusion, dissolution and osmotic gradient models were capable of fitting the data equally well. It was also possible to fit the data with a variety of parameter combinations, even if the values of some parameters were unlikely. We use the example of Paclitaxel release from the SIBS matrix to discuss important considerations in fitting controlled release data with mechanistic models.
TAXUS Express 冠状动脉支架由疏水性聚合物涂层（苯乙烯-异丁烯-苯乙烯共聚物，SIBS）提供持续剂量的疏水性药物（紫杉醇）。已知药物的浓缩颗粒分散在整个聚合物涂层中，但是药物从聚合物基质中逸出的机制尚未完全阐明。在这项工作中，应用数学模型对聚合物中 8.8%、25%和 35%载药量的体外控释数据进行了分析。测试了考虑不同释放机制的模型。观察到，菲克扩散、溶解和渗透压梯度模型都能够很好地拟合数据。即使某些参数的值不太可能，也可以用各种参数组合来拟合数据。我们以紫杉醇从 SIBS 基质中的释放为例，讨论了用机制模型拟合控释数据时的一些重要考虑因素。
