Box-Behnken效应面法优化苦参碱类脂囊泡的处方

Optimization on Formulation of the Matrine Noisomes by Box-Behnken Design and Response Surface Methodology

目的通过Box-Behnken试验设计,优选苦参碱类脂囊泡的最佳处方。方法采用3因素3水平Box-Behnken优化设计,逆向蒸发法制备苦参碱类脂囊泡,利用效应面法对影响包封率和载药量的因素进行考察,采用二次多项式模型描述各指标与因素间的数学关系,最后对优化处方进行验证。结果优化处方为:山梨醇酐单硬脂酸酯与胆固醇比例为2.64∶1,药物与类脂材料比例为1∶5.15,有机相水相比例为5∶1。制得的囊泡包封率为46.02%,载药量为13.20%。结论采用Box-Behnken效应面法得到了苦参碱类脂囊泡的优化模型,实现了处方优化,各项指标与预测值均能较好地吻合,模型选用合理有效。

OBJECTIVE To optimize the formulation of matrine niosomes by Box-Behnken design and response surface methodology. METHODS The matrine niosomes were prepared by the reverse-phase evaporation technique. The effects of the factors, such as the quality rate of sorbitan nonostearate and cholesterol, the quality rate of drug and lipid, the volume rate of organic phase and aqueous phase, on the entrapment efficiency, the drug loading rate were evaluated and optimized by Box-Behnken design. The mathematical relationship between the indexes and the factors was described by using the two polynomial model. RESULTS The optimal formulation was as follows： the ratio of sorbitan nonostearate and cholesterol was 2.64∶1, the ratio of drug to lipid was 1∶5.15, and the ratio of organic phase to aqueous phase 5∶1. In the optimized matrine niosomes formulation, the entrapment efficiency was 46.02%, the drug loading rate was13.20%. CONCLUSION Each index of the optimized matrine niosomes formulation is well fitted with the predicted value. Therefore, the adopted model is reasonable and effective.