Viridén Anna, Wittgren Bengt, Andersson Thomas, Larsson Anette
Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
Eur J Pharm Sci. 2009 Mar 2;36(4-5):392-400. doi: 10.1016/j.ejps.2008.11.003. Epub 2008 Nov 13.
Polymer release from hydrophilic matrix tablets, composed of hydroxypropyl methylcellulose, was studied for seven different polymer batches. A time difference of more than 80h between fully dissolved tablets was noticed although the batches were of the same pharmaceutical substituent (USP 2208) and viscosity (100 cps) grade. To find the functionality related parameters for polymer release from hydrophilic matrix tablets the polymer samples were characterised according to size and chemical composition. The size of the polymers was characterised by size-exclusion chromatography with multi-angle light scattering and refractive index detection. The average amount of substituents was measured with nuclear magnetic resonance and the distribution of the substituents along the cellulose chain was determined with high-performance anion-exchange chromatography with pulsed amperometric detection after acid and enzymatic hydrolysis. The results indicated that other types of interactions apart from entanglements were present between the polymer chains, which seemed to affect the polymer release. Most importantly, this study has shown a correlation between the polymer release and the substituent pattern, where the samples with slow release also were more heterogeneously substituted along the polymer chain. From this we can conclude that polymer release is very sensitive to alterations in chemical composition.
对由羟丙基甲基纤维素组成的亲水性基质片剂中七种不同聚合物批次的聚合物释放情况进行了研究。尽管这些批次具有相同的药物替代物（USP 2208）和粘度（100厘泊）等级，但完全溶解的片剂之间仍存在超过80小时的时间差异。为了找出亲水性基质片剂中聚合物释放的功能相关参数，根据聚合物样品的尺寸和化学成分对其进行了表征。聚合物的尺寸通过多角度光散射和折射率检测的尺寸排阻色谱法进行表征。用核磁共振测量取代基的平均量，并在酸和酶水解后，通过带有脉冲安培检测的高效阴离子交换色谱法测定取代基沿纤维素链的分布。结果表明，聚合物链之间除了缠结之外还存在其他类型的相互作用，这似乎影响了聚合物的释放。最重要的是，这项研究表明了聚合物释放与取代基模式之间的相关性，其中缓释样品在聚合物链上的取代也更不均匀。由此我们可以得出结论，聚合物释放对化学成分的变化非常敏感。
