采用均匀设计法研制多西紫杉醇聚山梨酯80/磷脂混合胶束注射液

Optimized Preparation of Docetaxel Polysorbate 80/Phospholipid Mixed Micelles Injection by Uniform Design

目的采用均匀设计法研制多西紫杉醇聚山梨酯80磷/脂混合胶束注射液。方法建立了多西紫杉醇聚山梨酯80磷/脂混合胶束的含量测定方法,利用"归一值"对多指标进行处理,通过均匀设计法对混合胶束配方及"归一值"建立数学模型,对比数论网格法,探讨效应面法优化均匀设计数学模型的可行性。结果从复相关系数及F检验看,均匀设计二次多项式回归模型优于多元线性回归模型,优化后的多西紫杉醇聚山梨酯80磷/脂混合胶束稳定时间长达3 d,平均载药率达到97.12%,平均粒径11.92 nm,以算术总评"归一值"建立的均匀设计二次多项式回归模型偏差为2.00%,以几何总评"归一值"建立的均匀设计二次多项式回归模型偏差为5.41%。结论优选出的多西紫杉醇聚山梨酯80磷/脂混合胶束稳定可行,可用于生产及临床,采用"归一值"也可以对均匀设计法中的多指标进行处理,对于二因素及三因素均匀设计建立的数学模型,也可以采用效应面法优化。

OBJECTIVE To optimize the preparation of the docetaxel polysorbate80 / phospholipid mixed micelles injection by uniform design.METHODS A HPLC method for the determination of docetaxel in polysorbate80/phospholipid mixed micelles solution was established.The multiple variables were optimized by desirability response,and the mathematic model was established.Comparing with the number theoretic net algorithm,the response surface methodology was used to optimize the uniform design mathematic model.RESULTS The second-order polynomial equation of the uniform design was prior to the multi-linear equation according to the multiple correlation coefficients.The optimized preparation stabilized for 3 d,the average entrapment efficiency was 97.12%and the average particles diameter was 11.92 nm,the variance of the arithmetic overall desirability response was 2.00%,the geometry one was 5.41%.CONCLUSION The optimized preparation is stable and practicable.The desirability response can be used to optimize the multiple variables in uniform design.The response surface methodology is feasible to optimize the two variables or three variables problem in uniform design.