文献分享 I 往复筒法测定双氯芬酸钠缓释片释放度的基本特征及其体外释放行为评价

往复筒法测定双氯芬酸钠缓释片释放度的基本特征及其体外释放行为评价

Basic Characteristics and in vitro Dissolution Behavior Evaluation of Diclofenac Sodium Sustained-release Tablets Determined by Reciprocating Cylinder

探索往复筒法测定双氯芬酸钠缓释片释放度的基本特征，建立往复筒法测定释放度检查方法，比较不同企业双氯芬酸钠缓释片体外释放曲线，评价其体外释放行为。

采用往复筒溶出仪，往复频率为10dips/min，上筛网目数为20目，下筛网目数为40目，停留时间为10s，滴水时间为60s，模拟人体胃肠道序贯性pH生理环境，经pH1.2盐酸溶液中释放2h后，再在pH4.5醋酸盐缓冲液中释放1h，最终在pH6.8磷酸盐缓冲液中释放 20h，对9家生产企业市售的双氯芬酸钠缓释片进行体外释放试验，在规定时间点取样后采用高效液相色谱法（HPLC）测定双氯芬酸钠缓释片的溶出量，绘制体外释放曲线。考察不同释放条件对体外释放行为的影响；对体外释放曲线进行模型拟合，考察其释放动力学及释药机制；同时通过计算相似因子（f2）评价其释放曲线相似性，评价体外释放行为。

A reciprocating cylinder dissolution instrument was used with a reciprocating frequency of 10 dips/min; the mesh number of the upper sieve was 20; the mesh number of the lower sieve was 40; the residence time was 10s, and the drip time was 60s, which simulated the sequential pH physiological environment of the human gastrointestinal tract. After being released in pH1.2 hydrochloric acid solution for 2h, then released in pH4.5 acetate buffer for 1h, and finally released in pH6.8 phosphate buffer for 20h, the in vitro release test of diclofenac sodium sustained-release tablet commercially available in 9 manufacturers was carried out, and the dissolution amount of diclofenac sodium sustained-release tablet was determined by HPLC method after sampling at the specified time point, and the in vitro dissolution curve was drawn. To investigate the effects of different release conditions on in vitro dissolution behavior; The model fitting of the in vitro dissolution curve was carried out to investigate its release kinetics and drug release mechanism. At the same time, the similarity of the dissolution curve was evaluated by calculating the similarity factor (f2), so then the dissolution behaviors in vitro were evaluated. 

生产企业A、B、D和F的双氯芬 酸钠缓释片体外释放曲线与参比制剂相似，其他生产企业均不相似；除生产企业G外，其他生产企业的双氯芬酸钠缓释片体外释放曲线以一级释放为最佳拟合模型；生产企业G的释放机制为Ⅱ相转运，其他生产企业的释放机制均为药物扩散和骨架溶蚀共同作用。

该方法可为双氯芬酸钠缓释片研发及质量一致性评价提供参考，也为往复筒法在缓控释制剂中的应用提供思路。

双氯芬酸钠缓释片；往复筒法；释放曲线；相似因子；释药机制

往复筒法测定双氯芬酸钠缓释片释放度的基本特征及其体外释放行为评价.pdf