星点设计-效应面法优化盐酸小檗碱胃漂浮小丸处方的研究  

Optimization of floating pellet containing berberine hydrochloride formulation by central composite design-response surface methodology

作　　者：张瑜[1] 杨磊[1] 

机构地区：[1]河南大学药物研究所,河南开封475004

出　　处：《中成药》2012年第2期251-257,共7页Chinese Traditional Patent Medicine

摘　　要：目的采用海藻酸钠与壳聚糖制备盐酸小檗碱聚电解质胃漂浮小丸,应用星点设计-效应面法优化其处方。方法将含盐酸小檗碱、制泡剂碳酸氢钠和壳聚糖的海藻酸钠溶液滴加至含醋酸的氯化钙溶液中,制得盐酸小檗碱胃漂浮小丸。通过单因素试验,选择海藻酸钠质量分数、碳酸氢钠质量分数为考察因素,小丸1、6、12 h的累积释药百分率和释药12 h的胃漂浮百分率为效应值,通过Design Expert8.0软件,采用星点设计安排实验,对各指标与因素进行数学模型拟合,采用效应面法预测优化处方,并对其进行验证。结果各指标与因素之间均采用二次多项式拟合,相关系数分别为0.970 8、0.960 8、0.964 9、0.952 4;优化处方制得胃漂浮小丸具有持续漂浮和缓慢释药特性,各指标实测值与预测值偏差在±5%以内。结论星点设计-效应面优化法可用于本制剂的处方优化,实现盐酸小檗碱胃漂浮小丸的胃内漂浮和缓慢释药特性。AIM To study the polyelectrolyte floating pellet containing berberine hydrochloride prepared with alginate and chitosan,and its formulation optimized by central composite design-response surface methodology.METHODS Sodium alginate solution added with berberine hydrochloride,sodium bicarbonate and chitosan was dripped into calcium chloride solution containing acetic acid,then berberine hydrochloride floating pellet was obtained.The influence factors including concentration of sodium alginate and sodium bicarbonate were chosen by one-factor experimental design.The evaluation parameters included the cumulative dissolution percentage of drug at 1 h,6 h,12 h and percentage of gastric retention at 12 h.Design Expert was used to optimizing the experimental conditions in mathematical model of response surface method,as compared with the predictive value.RESULTS The cumulative dissolution of drug at 1 h,6 h,12 h and percentage of gastric retention at 12 h were fix into second-order polynomial equation,regression coefficients of the four parameters were 0.970 8,0.960 8,0.964 9,0.952 4,respectively.The pellet prepared under the optimal condition had sustained-release and floating capability.Bias between the observed and predictive values of different parameters were within ±5%.CONCLUSION Central composite design-response surface methodology can be applied to optimizing the formulation and the model developed in this study is proved to be predictable.The floating and sustained-release characteristics of the floating pellets containing berberine hydrochloride are confirmed in vitro.

关 键 词：盐酸小檗碱 胃漂浮小丸 星点设计-效应面法 体外释药 

分 类 号：R944[医药卫生—药剂学]