星点设计-效应面法优化瑞德西韦/羟丙基-β-环糊精包合物的制备工艺

Optimization of Remdesivir/hydroxyl-β-cyclodextrin inclusion complex by central composite design-response surface method

以瑞德西韦/HP-β-CD包合物的包合率和收率的综合评分为考察指标,采用星点试验设计,考察HP-β-CD/瑞德西韦的摩尔比、包合温度和溶液pH对包合工艺的影响,采用多元线性回归、二次多项式和三次多项式进行拟合,优选最佳处方工艺;计算预测值与实际值偏差以评估拟合效果。结果显示:二次多项式拟合方程复相关系数(r)大于多元线性回归和三次多项式拟合方程,且接近1.0,表明二次多项式拟合度高、预测性好;预测得瑞德西韦/HP-β-CD包合物的最优包合工艺为HP-β-CD与瑞德西韦的摩尔比值8.0、包合温度27.5℃、溶液pH1.8,预测得包合率和收率分别为94.27%和96.23%;包合率和收率预测值与实际值偏差分别为2.11%和2.33%。因此,采用星点设计-效应面法能精确有效地优化瑞德西韦/HP-β-CD包合物的制备工艺,工艺稳定可行。

We used central composite design-response surface to optimize the preparation process of Remdesivir/hydroxyl-β-cyclodextrin inclusion complex.The effect was evaluated by the yield of inclusion and the yield inclusion complex.The indexes of HP-β-CD/Remdesivir molar ratio,temperature and pH were evaluated.The results were fitted by multi-linear equation,quadratic and cubic polynomial equation to optimize the inclusion process.We calculate the deviation between the predicted value and the actual value to evaluate the fitting.Results showed that the complex correlation coefficient(r)of quadratic polynomial equation was higher than that of multiple linear regression and cubic polynomial equation with the value close to 1.0,indicating that the quadratic polynomial had a high degree of fitting and good predictability.The optimal inclusion conditions for the preparation of Remdesivir/HP-β-CD inclusion compound were as follows:molar ratio of HP-β-CD and Remdesivir 8.0,inclusion temperature 27.5℃,pH 1.8.The predicted inclusion rate and yield were 94.27%and 96.23%,respectively.The deviations between the predicted value and the actual value of inclusion yield and the yield was 2.11%and 2.33%,respectively.Therefore,the central composite design-response surface method can precisely and effectively optimize the preparation of Remdesivir/HP-β-CD inclusion complex.The optimized process is stable and feasible.