Mechanistic aspects of the release of levamisole hydrochloride from biodegradable polymers

Abstract

The release of levamisole hydrochloride from poly-DL-lactide-co-glycolide compacts prepared at 5, 10 and 20% drug loading using two different particle size fractions of drug (90-125 and 125-250 microm) was investigated. Release profiles were significantly different from those previously reported for compacts 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 slower polymer degradation controlled release phase. The drug release profiles were successfully described by a model combining contributions from a first-order initial release phase and a polymer degradation controlled drug release 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 of the polymer-drug compact and this fraction tended to increase with increasing drug particle size, as expected from the model. The increase in F(B) with increased loading was attributed to the clumping of dispersed drug particles which effectively increased the proportion of drug linked to the compact surface.