Box-Behnken中心组合设计优化甘草酸二铵缓释片的处方

Optimized formulation of diammonium glycyrrhizinate sustained-release tablet by Box-Behnken design

目的考察甘草酸二铵缓释片的制备工艺,并对其体外释药机制进行研究。方法采用羟丙基甲基纤维素(HPM Ck4m)、山菕酸甘油酯为骨架材料,制备甘草酸二铵缓释片;使用Box-Behnken中心组合设计试验方案,借助试验设计软件Design Expert绘制响应面曲线图,筛选适合的处方;并通过方程拟合探讨释药机制。结果按预测处方制备的缓释片,在2、4、8、12 h的体外累积释放率均值分别为32.55%、49.94%、73.88%、97.89%。对其体外释药曲线进行模型拟合,结果表明药物的释放机制为扩散和骨架溶蚀二者的协同作用。结论验证试验证实了预测处方与实际处方之间具有较好的拟合度,Box-Behnken中心组合设计可以应用于甘草酸二铵缓释片处方的筛选。

Objective To investigate the preparation technique and optimal formulation of diammonium glycyrrhizinate sustained-release tablets and study the release mechanism of diammonium glycyrrhizinate release from the tablet. Methods Using HPMCk4m, Compritol 888 as skeleton material to prepare the diammonium glycyrrhizinate sustained-release tablet. To optimize the formulations by Box-Behnken design, and use Design Expert program for statistical analysis of experimental results. Release mechanism of diammonium glycyrrhizinate from sustained release tablets was established by equation fitting. Results The average accumulate release rates of diammonium glycyrrbizinate sustained-release tablets in 2, 4, 8, and 12 h were 32. 55%, 49.94%, 73.88%, and 97.89%. And the release of diammonium glycyrrhizinate could be controlled by diffusion associated with erosion. Conclusion Box-Behnken design could be successfully used to optimize the sustained-release tablet of diammonium glycyrrhizinate.