The present study aimed to investigate the effects of butyl stearate on t‑butoxyl paliperidone derivative (isoperidone)‑loaded poly(lactide‑co‑glycolide) (PLGA) microspheres. The mechanism of drug release rate delay by butyl stearate was examined by accelerated testing, morphological observation, thermal and fluorescence analyses. In vivo pharmacokinetic study was conducted on female beagle dogs. Spherical microspheres with smooth surfaces, small internal pores and shell structures were initially prepared. It was found that 3% (w/w) butyl stearate prolonged the in vitro drug release period from 46 to 82 days, and in vivo release period from 20 to 27 days. Furthermore, the results demonstrated that the green fluorescence imaging of isoperidone approaching the cores of microspheres with 3% butyl stearate was brighter than in microspheres without additives. In conclusion, it was shown that butyl stearate affected the microsphere structure, isoperidone microsphere distribution and isoperidone crystallinity. The results of the present study thus provide a potential method to develop sustained‑release preparations.
Keywords: poly (lactic-co-glycolic acid) microsphere; isoperidone; schizophrenia; butyl stearate; drug release rat.