星点设计-效应面法优化盐酸米诺环素口腔贴片处方

目的:应用星点设计-效应面法优化盐酸米诺环素口腔贴片的处方.方法:以羧甲基纤维素钠FSH6、卡波姆974PNF和交联羧甲基纤维素钠的用量为考察因素,分别以盐酸米诺环素在1、2、3h的累积释放度和粘附力为指标,采用线性方程和二次、三次多项式分别描述各时间点累积释放度及粘附力与3个考察因素之间的数学关系,根据其中一个较优数学模型绘制效应面图.各时间点累积释放度的效应面二维等高线图的最佳释放区域的重叠部分,与最佳粘附力的交集区域即为最佳处方区域,选择最佳处方,并进行预测分析.结果:采用二次项拟合的相关系数优于三次项拟合和线性方程,具有较高的可信度.盐酸米诺环素口腔贴片的优化处方为:羧甲基纤维素钠FSH6、卡波姆974P和交联羧甲基纤维素钠的用量分别为3mg、3.5mg和1.5mg.最佳处方在各时间点的释放度和粘附力的实测值在预测范围内.结论:由星点设计-效应面优化法建立的模型可以用于盐酸米诺环素处方的优化.

Optimization of minocycline hydrochloride mucosal adhesive tablet formulation using central composite design response surface method

Objective: To optimize the formulation of minocycline hydrochloride mucosal adhesive tablet using central composite design response surface method.Methods: The amounts of sodium carboxymethyl cellulose FSH6,Carbopol 974PNF and croscarmellose sodium were set as three independent variables;the dissolution of minocycline hydrochloride mucosal adhesive tablets at 1 h,2 h,3 h,and its bioadhesion force were taken as four dependent variables.Linear or nonlinear mathematic models were used to estimate the relationship between the independent and the dependent variables,with best fit mathematic model selected then.The optimized formulation was selected from the overlap of the contour graphs of the best release districts and appropriate bioadhesion force.Prediction was evaluated by comparing the observed and predicted values.Results: The second-order quadratic model had higher regression coefficient,compared with the third-order quadratic and linear models.Optimized formulation of minocycline hydrochloride mucosal adhesive tablet was proposed to consist 3.0 mg of sodium carboxymethyl cellulose FSH6,3.5 mg of Carbopol 974PNF and 1.5 mg of croscarmellose sodium.Dissolution and bioadhesion force of the optimized formulation were within the predicted values.Conclusion: Optimized formulation of minocycline hydrochloride mucosal tablet can be obtained by employing the established model based on central composite design response surface method.