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.