Reynolds T D, Gehrke S H, Hussain A S, Shenouda L S
College of Pharmacy, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0004, USA.
J Pharm Sci. 1998 Sep;87(9):1115-23. doi: 10.1021/js980004q.
Polymer erosion of matrices of similarly substituted hydroxypropyl methylcellulose (HPMC) polymers was examined, and drug release in terms of diffusion and erosion contributions was characterized, focusing on matrices containing either polymer alone or a drug content of 25% level with no added excipients. A novel approach was utilized to separate diffusional and erosional contributions to drug release. Diffusional drug release was determined by fitting release data versus (time)0.45, and the drug release due to erosion was quantified by subtracting the percent predicted for diffusional drug release from the total drug release at each specific time point. Drug release resulting from polymer erosion was linear versus time and was found to be a function of the number average molecular weight of the polymer. In contrast, diffusional release rates were comparable for all HPMC grades studied and, thus, were independent of number average molecular weight of the polymers studied. Under stirring conditions of 10-100 rpm as well as static condition, the detachment of individual polymer chains at the matrix surface occurred at a faster rate relative to diffusion away from the matrix surface. The erosion study indicated that polymer diffusion of the HPMC polymer chains through the aqueous diffusion layer was the rate-limiting step for polymer erosion. In general, polymer erosion was found to be inversely related to the polymer number average molecular weight. A scaling law was used to relate polymer erosion rate with the respective polymer number average molecular weight. Similar relationships were obtained for matrices with and without drug at a stirring rate of 100 rpm.
研究了类似取代的羟丙基甲基纤维素(HPMC)聚合物基质的聚合物侵蚀情况,并对药物释放的扩散和侵蚀贡献进行了表征,重点关注仅含聚合物或药物含量为25%且无添加辅料的基质。采用了一种新颖的方法来分离药物释放的扩散和侵蚀贡献。通过将释放数据与(时间)^0.45拟合来确定扩散性药物释放,并通过从每个特定时间点的总药物释放中减去扩散性药物释放预测的百分比来量化侵蚀导致的药物释放。由聚合物侵蚀导致的药物释放与时间呈线性关系,并且发现是聚合物数均分子量的函数。相比之下,所有研究的HPMC等级的扩散释放速率相当,因此与所研究聚合物的数均分子量无关。在10 - 100 rpm的搅拌条件以及静态条件下,相对于从基质表面扩散离开,基质表面单个聚合物链的脱离发生得更快。侵蚀研究表明,HPMC聚合物链通过水扩散层的聚合物扩散是聚合物侵蚀的限速步骤。一般来说,发现聚合物侵蚀与聚合物数均分子量成反比。使用标度定律将聚合物侵蚀速率与相应的聚合物数均分子量联系起来。在100 rpm的搅拌速率下,含药和不含药的基质获得了类似的关系。