Mechanistic aspects of the release of levamisole hydrochloride from biodegradable polymers

The release of levamisole hydrochloride from poly-DL-lactide-co-glycolide c ompacts prepared at 5, 10 and 20% drug loading using two different particle size fractions of drug (90-125 and 125-250 mum) was investigated. Release profiles were significantly different from those previously reported for co mpacts prepared using the base form of the drug. Release was found to occur in a biphasic manner, with an initial fast release phase followed by a slo wer polymer degradation controlled release phase. The drug release profiles were successfully described by a model combining contributions from a firs t-order initial release phase and a polymer degradation controlled drug rel ease phase. The fraction of drug released in the initial burst phase (F-B) was attributed to the dissolution of drug domains situated at the surface o f the polymer-drug compact and this fraction tended to increase with increa sing drug particle size, as expected from the model. The increase in F-B wi th increased loading was attributed to the clumping of dispersed drug parti cles which effectively increased the proportion of drug linked to the compa ct surface. (C) 2000 Elsevier Science B.V. All rights reserved.