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星点设计-效应面法优化琥珀酸美托洛尔缓释微丸处方 被引量:6

Formulation optimization of metoprolol succinate sustained release pellets using central composite design-response surface methodology
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摘要 目的:通过星点设计-效应面法优化琥珀酸美托洛尔( MS)缓释微丸处方工艺。方法采用蔗糖丸芯,以乙基纤维素为包衣材料,模型药物MS为致孔剂,通过流化床底喷工艺制备MS缓释微丸。以致孔剂比例和包衣增重为考察因素(自变量),微丸1,4,8,12,16 h的释放度为考察指标(因变量),采用两因素五水平星点设计对处方进行优化。根据自变量和因变量数据,进行数学方程拟合并描绘效应面,选择最佳处方工艺进行验证实验。结果与结论数学方程拟合结果表明二项式方程拟合度较高。根据效应面优化的最佳自变量范围可知,致孔剂比例为16%~18%,包衣增重为20%~25%。优化的缓释微丸药物释放度1 h达到9.15%,消除了释放初期的迟滞相,且能够在较长时间内维持良好的缓释作用。通过星点设计-效应面法优化的MS缓释微丸处方工艺稳定可行。 Objective To optimize the formulation of metoprolol succinate ( MS) controlled release pellets by central composite design-response surface methodology .Methods MS sustained-release pellets were prepared using sugar pellet cores as starter beads , ethyl cellulose as coating materials and MS itself as a pore former .The formulation of MS sustained-release pellets was optimized by a central composite design with two factors at five levels .These two factors ( two independ-ent variables) were the pore former level and coating level , and the evaluated indexes ( namely dependent variables ) included the in vitro cumulative release percentages of MS at 1, 4, 8, 12 and 16 h, respectively.Results and Conclusion The results of mathematical equation fitting suggested that the second-order quadratic model was the optimal fitting equa-tion.According to the response surfaces , the optimum values at the pore former level and coating level weve ranged from 16%to 18%and 20% to 25%, respectively .The in vitro cumulative release percentage of MS from the pellets at 1 h reached 9.15%,which consequently eliminated the lag phase in the initial release period and exhibited a good sustained-release effect.Central composite design-response surface methodology can be applied to optimizing the coating formulation for MS sustained release pellets .
出处 《军事医学》 CAS CSCD 北大核心 2014年第5期351-354,共4页 Military Medical Sciences
基金 国家科技重大专项资助项目(2012ZX09301003-001-009)
关键词 琥珀酸美托洛尔 膜控型 缓释微丸 星点设计 效应面法 metoprolol succinate coated pellets sustained release central composite design response surface methodology
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