A one-week subdermal delivery system for l-methadone based on biodegradable microcapsules

Abstract

Microspheres containing 13–16% l-methadone were prepared from three biodegradable polymers, poly( l-lactic acid), PLLA; poly (glycolic acid-co- l-lactic acid), PGLA; and poly (ϵ-caprolactone-co- l-lactic acid), PCL-LA, using the solvent evaporation method. The release of l-methadone from microspheres of PCL-LA (75–85 mol% l-lactic acid) was complete within 48 hours. Release from PGLA (80 mol% l-lactic acid) microspheres was almost as rapid, but 20% of the drug remained in the polymer matrix. Release from PLLA microspheres was subject to a 3–4 day induction period prior to loss of the drug over the next 5 days. This induction period for PLLA and the immediate release of l-methadone from PGLA microspheres were the result of an exceptionally large acceleration of the hydrolytic chain cleavage of the polymers in the presence of the basic drug. Measurements of the diffusion coefficients of l-methadone in the three polymers showed that only in the case of PCL-LA was Fickian diffusion responsible for the observed kinetics. Both blending and changes in the copolymer composition could be used to control the permeability and the induction period associated with l-methadone release from microspheres. It was possible to achieve zero-order release of l-methadone for six days by combining microspheres prepared from three different polymer compositions. Application of the Wurster process afforded polymer-coated l-methadone crystals (i.e., microcapsules) with an 80% drug loading.