国产与原研阿莫西林/克拉维酸钾片溶出度考察

目的：考察阿莫西林和克拉维酸钾在4种介质中的稳定性及自制阿莫西林/克拉维酸钾片、市售品和原研制剂在不同介质中的溶出曲线,分析体外释放行为.方法：采用已知含量的原料溶解于不同溶出介质中,在不同的时间段测定其色谱峰面积,考察其稳定性.参考日本橙皮书中阿莫西林/克拉维酸钾片溶出曲线的测定方法,以不同溶出介质对阿莫西林/克拉维酸钾片进行溶出曲线考察.采用f2因子进行比较分析.结果：克拉维酸在pH1.2、pH4.0溶出介质中1 h分别降解90%和3%,在水、pH6.8介质中8 h稳定;阿莫西林在pH1.2溶出介质中1 h降解3%,在水、pH4.0、pH6.8溶出介质中8 h稳定.C厂样品与B厂样品在不同溶出介质中溶出曲线均与A厂（原研）产品相似;C厂样品与B厂样品在pH1.2的盐酸溶液与pH4.0的醋酸缓冲溶液中前10 min的溶出速度较原研A药品快10%~20%.D厂样品、E厂样品在水介质下与原研样品不具有相似性.结论：克拉维酸溶液（pH1.2）稳定性极差;国内有些厂家产品在4种溶出介质中的溶出曲线与原研产品不一致,质量存在差异.

Comparative Analysis of in vitro Dissolution between Domestic Amoxicillin and Clavulanate Potassium Tablets and the Original Tablets

Objective： To inspect the stability of amoxicillin and clavulanate potassium clavulanic acid in 4 kinds of media, and analyze the dissolution curve in vitro of self-made amoxicillin clavulanic potassium tablets and the original products. Methods： Known concentration raw materials were dissolved in different dissolution media and measured the chromatographic peak a~a in different time period to study the stability. The dissolution curve of the tablets was inspected in different media according to the determination methods described in Japanese Orange Book. The dissolution difference between the tablets was compared by the f2 factor method. Results： The content of clavulanic acid respectively declined at the percentage of 90% in pH 1.2 and 3% in pH 4.0 after lh, while was stable in water and pH 6.8. The content of amoxicillin degraded 3% in pH 1.2 after 1 hour, while was stable in water, pH 4.0 and pH 6.8. The in vitro dissolution of the tablets from B and Cfactory was similar to that of the tablets from A factory （the original tablets）, and the dissolution rate in pH 1.2 and pH 4.0 was 10% -20% faster than the of the original tablets in the first 10 minutes, In water, the dissolution of D and E was different from that of A. Conclusion ： Clavulanic acid solution is unstable in pH 1.2 medium. There are differences in the quality between the domestic and the original products.