Box-Behnken设计-响应面法优化盐酸地芬尼多双层渗透泵控释片处方  

Formulation Optimization of Difenidol Hydrochloride Double-Layer Osmotic Pump Controlled-Release Tablets by Box-Behnken Design-Response Surface Methodology

作　　者：曾媛 刘辉 胡华 朱兰琼 ZENG Yuan;LIU Hui;HU Hua;ZHU Lanqiong(Department of Pharmacy of Medical Security Center,The General Hospital of Central Theater Command of the PLA,Wuhan,Hubei,China 430070;College of Pharmacy,Southern Medical University,Guangzhou,Guangdong,China 510515)

机构地区：[1]中国人民解放军中部战区总医院医疗保障中心药剂科,湖北武汉430070 [2]南方医科大学药学院,广东广州510515

出　　处：《中国药业》2022年第1期40-45,共6页China Pharmaceuticals

基　　金：国家“重大新药创制”科技重大专项[2018ZX09J18110-002];中国人民解放军联勤保障部队战勤部科研项目[CLB18J043]。

摘　　要：目的优化盐酸地芬尼多双层渗透泵控释片的处方。方法根据预试验结果,以含药层NaCl处方量、助推层聚氧乙烯(PEO)处方和包衣增重为自变量,以12 h累积释放度和释药曲线拟合度为因变量,采用Box-Behnken设计-响应面法筛选最佳处方并验证,并考察其稳定性。结果三次多项式模型为最佳拟合模型。盐酸地芬尼多双层渗透泵控释片的最优处方为,含药层NaCl每片10.50 mg,助推层PEO每片64 mg,包衣增重6.50%。所得3批样品的12 h累积释放度分别为80.14%,79.14%,78.08%,释药曲线拟合度分别为0.9735,0.9942,0.9828,且实测值与预测值无显著差异。稳定性考察结果表明,该制剂在高湿环境下稳定性较差,应置干燥、密闭环境保存。结论Box-Behnken设计-响应面法优选的处方合理,制得的盐酸地芬尼多双层渗透泵控释片具有显著的缓释特征,且稳定性较好。Objective To optimize the formulation of Difenidol Hydrochloride Double-Layer Osmotic Pump Controlled-Release Tablets.Methods According to the pre-test results,the NaCl content of the drug layer,the polyethylene oxide(PEO)content of the push layer and the weight gain of the coating layer were selected as independent variables,and the 12-hour cumulative release rate and the drug release curve fitting degree were taken as the dependent variables.Box-Behnken design-response surface methodology was used to screen the best prescription,and the verification test was carried out.The stability of the prescription was investigated.Results The cubic polynomial model was the best fit model.The optimal prescription of Difenidol Hydrochloride Controlled-Release Tablets was as follows:the NaCl content of the drug layer was 10.50 mg per tablet,the PEO content of the push layer was 64 mg per tablet,and the coating weight gain was 6.50%.The 12-hour average cumulative release of the three batches of optimized samples were 80.14%,79.14%,78.08%,respectively,the linear fits of the release curve R^(2) were 0.9735,0.9942,and 0.9828,respectively,and there was no significant difference between the measured and predicted values.The results of the stability test showed that the preparation had poor stability in a high humidity environment and should be stored in a dry and closed environment.Conclusion The optimized prescription screened by Box-Behnken design-response surface methodology is reasonable,and the prepared Difenidol Hydrochloride Double-Layer Osmotic Pump Controlled-Release Tablets have significant sustained-release characteristics and good stability.

关 键 词：盐酸地芬尼多 双层渗透泵控释片 Box-Behnken设计-响应面法 处方优化 稳定性 

分 类 号：R944[医药卫生—药剂学]