THE EFFECTS OF DRUG PHYSICOCHEMICAL PROPERTIES ON RELEASE FROM COPOLY(LACTIC GLYCOLIC ACID) MATRIX/

A study on the effect of physico-chemical properties of drugs on their release behavior from copoly (L-Iactic/glycolic acid) (PLGA) matrix w as performed. PLGA and drugs of acidic, neutral or basic nature were m ixed and molded by heat compression method into a cylindrical matrix. The release rate of drugs from the rod depended on their physico-chemi cal properties. Basic drugs were found to show high PLGA/aqueous mediu m partition coefficients (K-app), implying a strong ionic interaction with the polymer. This interaction kept these drugs dissolved in the m atrix during the release studies. The interaction shielded the polymer terminal carboxyl residues resulting in the slower matrix erosion, an d made the matrix less swellable, thus diminishing drug diffusion thro ugh the matrix. Consequently, K-app could be regarded as the determina nt parameter to evaluate the release rate of basic drugs. In contrast, acidic and neutral drugs had only weak interaction with PLGA, so that the drugs quickly precipitated out as crystals in the matrix during t he release studies. In this case, the drugs did not affect the matrix erosion, and hence the solubility of each drug in the hydrated matrix became the predominant parameter affecting drug diffusion. (C) 1998 El sevier Science B.V. All rights reserved.