SUSTAINED-RELEASE MICROSPHERES AND METHODS OF MAKING AND USING SAME

Provided, among other things, are compositions and methods for making sustained-release microspheres, as well as a microsphere delivery system for the sustained release of an active agent. The microsphere delivery system comprises a homogenous mixture of biodegradable polymer, active agent, and a so-called release-modifying agent (including a pH-stabilizing agent), and provides protected and sustained release of active agents from the microsphere delivery system. According to the invention, the microspheres preferably are produced by an oil-in-water emulsion method that involves the production of a homogeneous oil phase prepared by mixing active agent and a release-modifying agent, such as arginine, with biodegradable polymer, each dissolved in organic solvent. The homogeneous oil phase desirably is then dispersed in an aqueous phase containing an emulsifying agent, followed by solvent removal, to produce the microspheres in which the active agent and release-modifying agent are distributed homogeneously throughout the biodegradable polymer matrix.