Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
Int J Pharm. 2010 Apr 15;389(1-2):147-56. doi: 10.1016/j.ijpharm.2010.01.029. Epub 2010 Jan 25.
The purpose of this study was to gain further understanding of how the substituent heterogeneity of hydroxypropyl methylcellulose, HPMC, affects the polymer release from hydrophilic matrix tablets. The hypothesis was that the heterogeneous substituent pattern facilitated hydrophobic interactions that increased the viscosity and therefore affected the release rate to a major extent. Polymer tablets were prepared from three heterogeneously substituted HPMC batches of the same substituent (2208) and viscosity (100 cps) grade. To elucidate the hypothesis, fractions of both the dissolved polymer and the tablet residue were collected from the dissolution bath and further characterised. The extensive characterisation showed that, although the dissolved bath fraction and the tablet residue had a similar average degree of substitution, the residue was more heterogeneously substituted. It was further revealed that the heterogeneous substituent pattern of the tablet residue facilitated the formation of soluble gel-like components already at room temperature, which increased the viscosity. The viscosity increased by 150% at temperatures correlated to the dissolution bath, and it was thus concluded that the gel-like components grew in size with temperature. Finally, much lower release rates were obtained by tablets composed of the residue compared to tablets composed of the bath fraction, which clarified the hypothesis.
本研究旨在深入了解羟丙基甲基纤维素（HPMC）取代基的异质性如何影响亲水性基质片剂中聚合物的释放。假设是，异构取代基模式促进了疏水相互作用，从而极大地增加了粘度并因此影响了释放速率。从相同取代基（2208）和粘度（100 cps）级别的三个异质取代的 HPMC 批次制备聚合物片剂。为了阐明假设，从溶解浴中收集溶解聚合物和片剂残余物的部分，并进一步进行表征。广泛的表征表明，尽管溶解浴部分和片剂残余物具有相似的平均取代度，但残余物的取代基更异构。进一步揭示了片剂残余物的异构取代基模式有利于在室温下形成可溶性凝胶状成分，从而增加了粘度。在与溶解浴相关的温度下，粘度增加了 150%，因此可以得出结论，凝胶状成分随温度而增大。最后，由残余物组成的片剂的释放速率比由浴部分组成的片剂低得多，这证实了假设。
