中心组合效应面设计优化盐酸小檗碱包合物的制备

Optimization of berberine and β-cyclodextrin inclusion compound preparation by central composite design

目的探讨中心组合效应面设计在优化盐酸小檗碱-β-环糊精包合物过程中的应用。方法以盐酸小檗碱为模型药物,应用中心点效应面实验设计(central composite design,CCD),采用饱和水溶液法制备盐酸小檗碱-β-环糊精包合物,通过相溶解度图法,溶出速度及饱和溶解度的测定对所制备的包合物进行验证。结果通过CCD设计建立二项式数学模型所优化包合物的处方为药物与包合材料的比例为1∶2.03,包合时间为2.29 h。包合常数为263.01 L/mol。与盐酸小檗碱相比较,溶解度可以提高2.98倍。结论 CDD设计可认为是寻求盐酸小檗碱-β-环糊精包合物的最佳制备工艺,形成包合物后可显著提高药物的溶解度。

Objective To investigate application of central composite design（CCD） to optimize berberine- β-cyclodextrin inclusion compound. Methods CCD optimization method was performed during the preparation of berberine-β-cyclodextrin inclusion compound. The inclusion compound was tailored according to saturated aqueous solution method. The product was validated via phase solubility diagram,dissolution rate and saturated solubility. The binding constant at 25 ℃ was calculated. Results The optimal conclusion can be inferred from CCD. Multivariate quadratic equations were used to analyze interaction effects between the multivariate factors. The ratio of drug：β-cyclodextrin served as 1：2.03,and the including period was 2.29 h,respectively. The binding constant was 263.01 μmol at 25 ℃. The solubility of inclusion compound was 2.98 times compared with raw berberine. Conclusion CCD was suitable to optimize the formulation of preparation of inclusion compound. The berberine- β-cyclodextrin inclusion compound exerts superior performance in improving dissolution properties.