Microesferas de liberación sostenida y métodos de fabricación y uso de las mismas

Un sistema de administración de microesferas para la liberación sostenida de un agente activo, comprendiendo dicho sistema de liberación un polímero biodegradable, un agente activo y un aminoácido básico, en el que dicho agente activo y el aminoácido básico se distribuyen de forma uniforme en y a través de dicha matriz de polímero, en el que dicho aminoácido básico estabiliza dicho agente activo y potencia su liberación sostenida, y en el que dicho sistema de liberación comprende además un ácido orgánico distribuido de forma uniforme en y a través de dicha matriz de polímero. 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.