星点设计-效应面法优化仑伐替尼混合胶束的制备工艺

Optimization of the preparation process for lenvatinib mixed micelles by central composite design-response surface methodology

目的优化仑伐替尼混合胶束的处方及其制备工艺。方法以Pluronic P123和F127作为载体材料,通过薄膜水化法制备仑伐替尼混合胶束。利用单因素实验和星点设计-效应面法筛选出最优处方并对其物理性质进行初步表征。结果优化后的最佳处方和工艺条件为:P123质量百分比80%、载体材料用量90 mg、投药量10 mg、水化体积6 ml、水化时间45 min、旋蒸温度55℃。制备得到的仑伐替尼混合胶束的平均粒径为(104.0±0.32)nm,PDI为0.22±1.19,Zeta电位为(-2.56±0.81)mV,平均包封率为83.33%±0.30%,平均载药量为8.67%±0.07%。胶束形态为分布均一的规整球形,并显示出一定的缓释性能。结论该研究开发的制备工艺简单可行,所得载药胶束具有较高的载药量和包封率且释放稳定,为仑伐替尼混合胶束的进一步研究和开发提供了有价值的参考。

Objective To optimize the formulation and preparation process of lenvatinib mixed micelles.Methods Hybrid micelles of lenvatinib were prepared by film hydration method,with Pluronic P123 and F127 as carrier materials.Optimal formulation was selected through single-factor experiments and central composite design-response surface methodology,and preliminary characterization of its physical properties was conducted.Results The optimized formulation and process conditions were identified as follows:P123 mass percentage of 80%,carrier material amount of 90 mg,drug loading of 10 mg,hydration volume of 6 ml,hydration time of 45 min,and rotary evaporation temperature of 55℃.The resulting lenvatinib mixed micelles had an average particle size of(104.0±0.32)nm,a polydispersity index(PDI)of 0.22±1.19,and a Zeta potential of(−2.56±0.81)mV.The average encapsulation efficiency was 83.33%±0.30% and the average drug loading was 8.67%±0.07%.The micelles displayed a uniform spherical morphology with a certain sustained-release capability.Conclusion The preparation process developed in this study was simple and feasible and produced drug-loaded micelles with high drug loading and encapsulation rates,and stable release,which could provide valuable insights for further research and development of lenvatinib mixed micelles.