Provided, among other things, are compositions and methods for makingsustained-release microspheres, as well as a microsphere delivery system forthe sustained release of an active agent. The microsphere delivery systemcomprises a homogeneous mixture of biodegradable polymer, active agent, and aso-called release-modifying agent (including a pH-stabilizing agent), andprovides protected and sustained release of active agents from the microspheredelivery system. According to the invention, the microspheres preferably areproduced by an oil-in-water emulsion method that involves the production of ahomogeneous oil phase prepared by mixing active agent and a release-modifyingagent, such as arginine, with biodegradable polymer, each dissolved in organicsolvent. The homogeneous oil phase desirably is then dispersed in an aqueousphase containing an emulsifying agent, followed by solvent removal, to producethe microspheres in which the active agent and release-modifying agent aredistributed homogeneously throughout the biodegradable polymer matrix.
