D-最优混料设计优化尼莫地平骨架片的处方

Optimization the Formulations of Nimodipine Matrix Tablet Using D-Optimal Mixture Design

目的通过D-最优混料设计优化尼莫地平骨架片的处方。方法以羟丙甲基纤维素(HPMC)、海藻酸钠和乳糖的用量为考察因素,分别以3,6,9和12h取样时间点的体外累积释放度为考察指标,选用最佳的数学模型描述考察指标和考察因素之间的数学关系,并绘制等高线图;以设定的3,6,9和12h的累积释放度为目标值,通过等高线叠加图预测最优处方,最后对最优处方进行验证。结果由最佳回归模型可知3个考察因素和4个考察指标之间存在可信的定量关系;5个验证处方骨架片体外释放的实验值与预测值非常接近;经相似因子(f2)检验,最优处方骨架片的释药曲线与零级释药曲线基本一致。结论D-最优混料设计可用于尼莫地平骨架片处方的优化,所建立的数学模型具有准确的预测性。

OBJECTIVE To optimize the formulations of nimodipine matrix tablet using D-optimal mixture design. METHODS Independent variables were the amounts of HPMC, sodium alginate and lactose, and drug accumulated release at 3, 6, 9 and 12 h were dependent variables. Optimal mathematical models were chosen to estimate the relationship between the dependent and the independent variables, and to delineate triangular-dimensional contour plots. With appointed drug release at 3, 6, 9 and 12 h as target values, overlay plot was used to predict the optimal formulation. Validation of optimal formulation was verified at last. RESULTS In optimal regression models, there are reliable quantitative relationships between three factors and four evaluation indexes. In vitro release test of five optimal checkpoint formulations indicated that there existed high approximation between their predicted and experimental values. The values of similarity factor （f2） indicated the equivalence to the release profile of the optimum formulation and zero-order release profile. CONCLUSION D-optimal mixture experimental design facilitated the optimization of nimodipine matrix formulations. Optimal models are proved to have the ability of high prognostic and feasible.