Naltrexone microspheres: in vitro release and effect on morphine analgesia in mice.

ABSTRACT

AIM: To study in vitro release and in vivo effect of four different types of sustained-release naltrexone microspheres on morphine analgesia. METHODS: Release of naltrexone from four types of biodegradable microspheres was investigated by HPLC. Their antagonist effects on morphine analgesia were observed using mouse hot-plate procedure. RESULTS: Poly latide-co-glycolide (PLGA) composition had a remarkable effect on naltrexone release from microspheres and its antagonism towards morphine analgesia. Two formulations of PLGA 5050 formulation released more than 80 % of total naltrexone and lost their antagonism by 8 d. The PLGA 7525 formulation with 20 % and 30 % drug loadings did not release 95 % of total drug and lose antagonism until 40 d and 30 d, respectively. Increasing the drug loading enhanced naltrexone release from microspheres and seemed to shorten the analgesic antagonistic effect of naltrexone. CONCLUSION: Antagonism by naltrexone microspheres towards morphine analgesia correlates well with the drug release in vitro.