Studies onin vitroavailability, degradation, and thermal properties of naltrexone-loaded biodegradable microspheres

PURPOSE: Following the report that continuous exposure of naltrexone (NTX) to drug-dependent pregnant women is safe and effective, the work was designed to develop NTX-loaded controlled delivery systems capable of making NTX available from 1 month to 4 months or greater by a single parenteral administration. Such drug-delivery systems will be useful in alleviating problems such as fetal alcohol syndrome in pregnant women and other problems associated with alcoholism. METHODS: These studies were designed to investigate in vitro drug availability and microsphere degradation (investigated by gel permeation chromatography (GPC) peak areas of water-soluble fragments released into incubation medium, changes in molecular weight with degradation time, and changes in the glass transition temperature with degradation time) of NTX-loaded poly(D,L-lactide-co-glycolide) (PDLLAGA) microspheres. RESULTS: Data showed that in vitro drug availability and degradation were affected by the initial molecular weight of the copolymers, the type of copolymers (lactide-co-glycolide ratio), the source of the polymer (the manufacturer), and the nature of the drug (anhydrous versus regular NTX). CONCLUSION: Drug-development scientists interested in NTX-loaded microspheres for the design of controlled release devices using these polyesters should take adequate cognizance of the variables that affect drug availability from NTX-loaded microspheres. The copolymers are suitable for the fabrication of NTX-loaded microspheres capable of sustained drug release from 30 to 150 days.