Naltrexone microspheres: in vitro release and effect on morphine analgesia in mice.
OBJECTIVE
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 50:50 formulation released more than 80 % of total naltrexone and lost their antagonism by 8 d. The PLGA 75:25 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.


CONCLUSIONS
Antagonism by naltrexone microspheres towards morphine analgesia correlates well with the drug release in vitro.
He
G A
GA
National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China. ghe@mail.mdanderson.org
Hou
H M
HM
Liu
X J
XJ
D000698:Analgesia; D000818:Animals; D003692:Delayed-Action Preparations; D005260:Female; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D009020:Morphine / Q000037:antagonists & inhibitors*; D009271:Naltrexone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009271:Naltrexone; D009020:Morphine