丁苯酞-磺丁基醚-β-环糊精包合物制备工艺优化

Technology Optimization of Preparation Process of Butylphthalide Sulfobutyl Ether-β-cyclodextrin Inclusion Complex

目的优化丁苯酞-磺丁基醚-β-环糊精包合物的制备工艺。方法采用冷冻干燥法制备丁苯酞-磺丁基醚-β-环糊精包合物,将丁苯酞包合率作为指标,采用星点设计法,设定三因素五水平考察包合温度、包合时间、磺丁基醚-β-环糊精与丁苯酞投料比对包合工艺的影响,并分别进行多元线性、二项式方程和三项式方程拟合,建立模型,效应面法选取最优工艺。结果丁苯酞-磺丁基醚-β-环糊精包合工艺为:包合温度67℃、时间2.09 h、磺丁基醚-β-环糊精与丁苯酞投料比2.6∶1,丁苯酞的包合率预测值与实际值的偏差为2.4%。结论以星点设计-效应面法建立的数学模型预测效果良好,该方法适用于丁苯酞-磺丁基醚-β-环糊精包合物的制备工艺优化。

Objective To optimize preparation process of butylphthalide sulfobutyl ether-β-cyclodextrin inclusion complex. Methods Freeze-drying method was adopted to prepare butylphthalide sulfobutyl ether-β-cyclodextrin inclusion complex. Inclusion ratio was served as index,the effects of inclusion temperature,inclusion time and the ratio of sulfobutyl ether-β-cyclodextrin to butylphthalide on the inclusion process were investigated by using response surface method. The optimal inclusion process was predicted according to the formulation which was established and fitted by multi-linear equation,secondorder polynomial equation and the third-order polynomial equation. Results The optimum inclusion technology of butylphthalide sulfobutyl ether-β-cyclodextrin inclusion complex was as follows： inclusion temperature was 67 ℃,inclusion time was 2.09 h,the input ratio of sulfobutyl ether-β-cyclodextrin to butylphthalide was 2. 6 ∶ 1. The deviation of inclusion ratio between actual value and predicted value was 2.4%. Conclusion Mathematical model established by central composite design and response surface method has a good prediction,which can be used to optimize the preparation process of butylphthalide sulfobutyl ether-β-cyclodextrin inclusion complex.