Study On Preparation And Release Behavior Of Porous Sustained-release Microspheres Of Exenatide

ObjectiveThe aim of this study is to develop the microspheres of exenatide(EXT)with high encapsulation efficiency,low burst release and low hysteretic release effect.MethodsThe quantitative analysis of EXT in vitro was carried out by micro-BCA method.W/0 colostrum of EXT was prepared by ultrasound,then W/O/W composite emulsion was prepared by microfluidic technology.EXT microspheres were prepared by further stirring and solidification.With the drug loading,encapsulation efficiency,particle size,span and in vitro release of EXT microspheres as indicators,the conditions of porogens,solvents and protective agents were investigated by single factor,and the formulation process of EXT microspheres was optimized to determine the optimal formulation of porous microspheres and porous microspheres..EXT microspheres were characterized by scanning electron microscopy(SEM)and differential scanning calorimetry(DSC).To investigate the release characteristics of EXT microspheres in vitro and evaluate the pharmacokinetic behavior of EXT microspheres in SD rats after subcutaneous administration.Results(1)The results of methodological validation showed that the micro-BCA method was suitable for the determination of EXT in this experiment,with good accuracy,precision and recovery.(2)By single factor investigation,the formulation of EXT porous microspheres was PLGA 50/50,PLGA concentration was 100 mg/mL,ratio of EXT:PLGA was 1:15,ammonia bicarbonate concentration was 6%,sucrose concentration was 2%;(3)The average drug loading of EXT porous microspheres was 5.50±0.07%,the average encapsulation rate was 91.67±0.07%and the average particle size was 84.31±3.57 u m(4).The average burst release rate was 14.22±3.79%and the cumulative release rate was 93.35±4.43%in 5 weeks.(5)The characterization results of EXT microspheres showed that the prepared microspheres were uniform in size,round in shape,smooth in surface and porous in interior.(6)Pharmacokinetic results showed that the peak time of EXT porous microspheres was 2 h,the peak concentration was(86.05±6.39)ng·mL-1,and the AUC0-38 value was(293.41±28.12)ng·mL-1·d.The drug concentration remained stable within 2 weeks and continued to release for 30 days.ConclusionBased on microfluidic technology,porous microspheres of EXT were prepared by W/0/W method.Experiments in vitro confirmed that EXT could release smoothly and completely within 5 weeks.Pharmacokinetic results in rats showed that the burst release rate was stable and the phenomenon of delayed release was avoided.EXT porous microspheres have high encapsulation efficiency and spherical shape.It has good research significance and application prospects.