目的 优选海蒙制酸胃漂浮缓释片的最优处方配比,并考察其体外释药特征。方法 利用Plackett-Burman设计实验,以CaCO₃在2、6、12 h累积释放率的综合评分为指标,筛选出影响缓释片制备的3个主要影响因素:骨架材料、助漂剂、填充剂,并确定非主要影响因素的水平。在此基础上,利用Box-Behnken中心复合原理设计3因素3水平实验,以累积释放率为指标优选处方,并利用响应优化器优化实验结果,拟合释药动力学方程。结果 优化后的最佳处方为海螵蛸225.0 mg、蒙脱石25.0 mg,加入辅料羟丙基甲基纤维素(HPMC K100M)100.0 mg、微晶纤维素(MCC)48.3 mg、乙基纤维素(EC)25.0 mg、十八醇74.7 mg,5%聚乙烯吡咯烷酮(PVP-K30)的乙醇溶液作黏合剂。用Minitab优化方案制得的缓释片与模型预测值基本一致,所制备片剂的漂浮时间在人工胃液中均能持续12 h以上,体外释药符合一级释药模型。结论 海蒙制酸缓释片处方合理,制备工艺可行,12 h内有良好的体外释药性。

Objective To optimize the formulation of Haimeng Zhisuan gastric floating sustained-release tablets and to investigate its in vitro release properties. Methods Plackett-Burman design was used to screen three most influential factors, i.e. matrices, floating material, and fillers which had significant impact on the preparation of floating sustained-release tablet by evaluating the cumulative release rate of CaCO₃ at 2, 4, and 12 h;The levels of non-important factors were also determined. A 3-factor, 3-level Box-Behnken design was led to optimize the formulation, using cumulative release rate as index. The experiment result was optimized and the drug release kinetics equation was fitted by response optimizer. Results The optimized tablet formulation was as follows: cuttlebone 225.0 mg, Montmorillonite 25.0 mg, HPMC K100M 100.0 mg, MCC 48.3 mg, EC 25.0 mg, searyl alcohol 74.7 mg, and 5% PVP-K30 ethanol solution as adhesive. The experimental data of optimized tablet were similar to the predicted values. The floating duration was over 12 h in simulated gastric fluid. Data of the in vitro release were fitted to the first-order equation. Conclusion Formulation of Haimeng Zhisuan floating sustained-release tablet is found to be reasonable. The preparation technology is feasible. The tablet shows good in vitro release properties within 12 h.

科技部重大新药创制项目:现代中药创新集群与数字制药技术平台(2013ZX09402203)