星点设计-效应面法优化富马酸美托洛尔脉冲控释片最佳处方  

Optimization of pulsatile-controlled release tablets of metoprolol fumarate by central composite design-response surface methodology

作　　者：张栋[1] 孙晓燕 顾纪锋 李爱国[1] 王德凤[1] 黄桂华[1] 

机构地区：[1]山东大学药学院,山东济南250012 [2]山东鲁银药业有限公司,山东烟台264002 [3]上海五官科医院药剂科,上海200031

出　　处：《中国生化药物杂志》2011年第1期14-18,共5页Chinese Journal of Biochemical Pharmaceutics

摘　　要：目的用数学方法将实验设计中的多指标归一化,确定富马酸美托洛尔脉冲控释片的优化处方。方法以崩解剂用量(mg)、羟丙甲纤维素(HPMC)用量(mg)、包衣膜厚度(%)、PEG6000用量(mg)、Eudragit L100用量(mg)为自变量,5,7,12和16 h的累积释放百分率为因变量,计算总评归一值,分别进行多元线性和非线性拟合,按非线性拟合方程描绘三维效应面,从效应面上选取对总评归一值较佳的实验处方范围。结果总评归一值的多元非线性拟合方程优于多元线性回归方程,优化后模型的复相关系数较高,R2=0.929 2,以优化处方制备的脉冲控释片总评归一值为0.834 0,与理论预测值的偏差为-4.35%。结论星点设计-效应面法可以准确快速地优化富马酸美托洛尔脉冲控释片的处方。Purpose To determine the optimal formulation of explosion pulsatile-controlled release tablets of metoprolol fumarate(MF).Methods The formulation was optimized using central composite design and response surface metholodgy.The effects of five independence variables,HPMC(mg),Eudragit L100(mg),PEG6000(mg),disintegrants(mg),and thickness of the coating films(%) were evaluated.Response variables selected in the research were percent of accumulated release(Q) of 5,7,12,16 h.The data were transformed into desirabilities.Overall desirability was calculated from the geometric mean of the four desirabilities of each formulation.The second-order polynomial and linear equations were fitted to the data of overall desirabilities,and the resulting equation was used to produce 3-D response surface graphs,through which the optimal formulation was predicted.Results The second-order polynomial equation was superior to the linear one,and regression coefficient of the nonlinear estimation was higher than 0.929 2.The pulsatile-controlled release tablets prepared according to the optimal experimental conditions resulted in an overall desirability of 0.834 0.The bias between observed and predicted values of the overall disrability of the optimal formulation was-4.35%.Conclusion Central composite design-response surface methodology is successfully used to optimize the formulation of MF pulsatile-controlled release tablets

关 键 词：富马酸美托洛尔 星点设计-效应面法 脉冲控释 

分 类 号：R944.9[医药卫生—药剂学]