星点设计-效应面法优化利托那韦片处方

Optimization of ritonavir tablets prescription by central composite design-response surface methodology

目的:星点设计-效应面优化法设计利托那韦片最佳处方,以溶出度法验证与原研药的体外一致性。方法:采用热熔挤出法制备利托那韦固体分散体,与无水磷酸氢钙、胶态二氧化硅混合,然后向其加入硬脂富马酸钠,充分混合后,直接压片,采用星点设计-效应面法以无水磷酸氢钙、硬脂富马酸钠、胶态二氧化硅加入量为影响因素,以总混后物料的流动性、压片过程中的适用性综合评分为响应值进行多元线性回归和多元非线性回归拟合并绘制效应面与等高线图,筛选出最优处方,并与原研片在同一溶出条件下进行验证。结果:获得利托那韦片最佳处方且与原研片体外溶出一致。结论:采用星点设计-效应面法建立的模型预测性良好,可很好地进行利托那韦片处方优化,获得与原研片体外溶出一致的利托那韦片。

Objective:To design the optimal prescription of ritonavir tablets using the central composite design-response surface methodology and verify the in vitro consistency with the reference list drug by dissolution method.Methods:The ritonavir solid dispersion was prepared by the hot melt extrusion method,mixed with anhydrous calcium hydrogen phosphate and colloidal silica.Then,sodium stearyl fumarate was added to it.After fully mixing,the mixture was directly pressed into tablets.The central composite design-response surface method was used to draw the response surface and contour map with the addition of anhydrous calcium hydrogen phosphate,sodium stearyl fumarate,and colloidal silica as the influencing factors,and the comprehensive score of the fluidity of the total mixed materials and the applicability in the tableting process as the response values.The optimal prescription was screened and verified under the same dissolution conditions as the reference list drug.Results:The best formulation of ritonavir tablets was obtained,consistent with the dissolution of the reference list drug in vitro.Conclusion:The model established by central composite design-response surface methodology has good predictability,the formula of ritonavir tablets can be well optimized,and the dissolution of ritonavir tablets in vitro is consistent with that of the reference list drug.