Study on the Formulation Optimization of Entecavir PLGA Sustained-release Microspheres and Its Drug Release in vitro / 中国药房

ABSTRACT

OBJECTIVE:To optimize the formulation of entecavir PLGA sustained-release microspheres,and explore its drug release in vitro. METHODS:PLGA sustained-release microspheres was prepared by emulsification-solvent evaporation method. Us-ing composite score of entrapment efficacy and drug loading as indexes,orthogonal test was designed to optimize drug amount, drug-PLGA mass ratio,PLGA mass concentration,oil phase-aqueous phase volume ratio and polyvinyl alcohol (PVA) concentra-tion;and validation test was also conducted. The prepared microsphere morphology,particle size and durg release in vitro were de-tected. RESULTS:The optimized formulation was entecavir 20 mg,entecavir-PLGA mass ratio 1∶10,PLGA mass concentration 200 mg/ml,oil phase-aqueous phase volume ratio 1∶10,and PVA concentration 2%;entrapment efficacy was (86.52 ± 3.25)%, drug loading was(18.36±1.37)%,RSDs were lower than 5.0%(n=3);it was round and smooth in appearance with average par-ticle size of 58.35 μm;Q10 h,Q96 h and Q360 h were 9.6%,42.9% and 89.6%,and the drug release in vitro fitted to Higuchi model (r2=0.965 8). CONCLUSIONS:Entecavir PLGA sustained-release microspheres prepared by optimized formulation has good sus-tained-release performance.