星点设计-效应面法优化非洛地平双层渗透泵控释片

Optimization of push-pull osmotic pump controlled release tablets containing felodipine by central composite design-response surface methodology

目的:通过星点设计-效应面法优化非洛地平双层渗透泵控释片处方。方法:以含药层片芯中氯化钠、助推层聚氧化乙烯用量、羟丙甲基纤维素用量、包衣液中醋酸纤维素与PEG4000的比例及包衣增重为自变量,以2,8,12,16h的累积释放度为考察指标,计算总评归一值,分别进行多元线性和非线性拟合,根据模型绘制效应面和等高线图及设定的2,8,12,16h释药目标值及总评归一值,确定优化处方,最后进行验证。结果:二次多项式模型比多元线性模型置信度高;优化处方各设定指标的预测值和测定值非常接近。结论:采用星点设计-效应面法,得到了基于二次多项式模型的非洛地平双层控释片处方优化模型,实现了该控释片的处方优化。

OBJECTIVE To optimize the formulation of push pull osmotic pump controlled release tablets containing teloalpine by the central composite design-response surface methodology. METHODS In the formulation design, the effects of five independence variables,the amount of NaCl,PEO,HPMC K4M, the ratio of cellulose to PEG 4000, tablet weight gain for membrane coating, were evaluated. Response variables selected in the research were in vitro cumulative releases at 2,8,12 and 16 h. The data were transformed in desirabilities. Overall desirability was calculated from the geometric mean of the four desirabilities of each formulation. Muhilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and contour plots in order to select the optimal formulations. RESULTS The optimized area predicted by quadratic model had better prediction capability than that by muhilinear model. In vitro release test indi- cated that there existed high approximation between the observed and estimated values. CONCLUSION The multi-objective simultaneous optimization of push pull osmotic pump controlled release tablets containing felodipine could be achieved by the central composite design and response surface methodology.