Box-Behnken设计-效应面法优化盐酸阿夫唑嗪胃漂浮控释骨架片的处方

Application of Box-Behnken design response surface methodology to optimize the formulation of alfuzosin hydrochloride gastric floating controlled-release matrix tablets

目的应用Box-Behnken设计-效应面法优化盐酸阿夫唑嗪胃漂浮控释骨架片的处方。方法采用干法压制包衣技术制备盐酸阿夫唑嗪胃漂浮控释骨架片;以骨架片包衣层中药物含量、包衣层中HPMC K100M和碳酸氢钠的用量为考察因素,以体外漂浮性能、2 h药物累积释放度和零级释放动力学模型决定系数R^2为评价指标;采用三因素三水平的Box-Behnken设计效应面法筛选胃漂浮控释片的最优处方,并进行验证。结果最优处方为包衣层中药物含量为40%、包衣层中HPMC K100M和碳酸氢钠的用量分别为53%和12%。按最优处方制备的胃漂浮控释片起漂时间小于5 min,续漂时间大于24 h,2 h药物累积释放度为8.34%,零级释放动力学模型决定系数R^2为0.994 4,预测值与实测值相对误差小于5%。结论 Box-Behnken设计-效应面优化法可用于胃漂浮控释片的处方优化,所建立的数学拟合模型预测性良好。

Objective To optimize the formulation of alfuzosin hydrochloride gastric floating controlled-release matrix tablets using Box-Behnken design response surface methodology.Methods The alfuzosin hydrochloride gastric floating controlled-release matrix tablets were prepared by dry compression coating technique.The content of drug(X1,%)in coating layer,the concentration of HPMC K100 M(X2,%)and NaHCO3(X3,%)of the coating layer were selected as independent variables.The floating lag time(FLT,Y1,min),total floating time(TFT,Y2,h),the accumulated drug release in 2 h(Q2,Y3,%)and the determination coefficient R2 of zero-order kinetics model(R-sqr,Y4)were selected as dependent variables.A 33 Box-Behnken design was used to optimize the formulation in the present study and the chosen mathematical model would be validated.Results The content of drug in coating layer,the concentration of HPMC K100 M and NaHCO3 in the coating layer of the optimized formulation were 40%,53%and 12%,respectively.The floating lag time was less than 5 min,the total floating time was more than 24 h,the accumulated drug release in 2 h was 8.34%,and the determination coefficient R2 of Zero-order release kinetics model was 0.994 4.The relative error between predicted value and experiment value was less than 5%.Conclusion The Box-Behnken design response surface methodology could be used to optimize the formulation of alfuzosin hydrochloride gastric floating controlled-release matrix tablets with the good predictability.