The aim of this study was to prepare and characterize a controlled-release system (microspheres) loaded with ibuprofen, for intra-articular administration, to extend its anti-inflammatory effect in the knee joint cavity. Among the bioresorbable polymers employed, poly(D,L-lactic-co-glycolic) acid (PLGA) (13137 Da) was chosen because of its high biocompatiblity. Microspheres were produced by the solvent evaporation process from an O/W emulsion. Labrafil M 1944 CS was included in the formulation as an additive in order to modulate the release rate of the non-steroidal anti-inflammatory drug (NSAID). Once prepared, the microspheres were sobre-sterilized by gamma-irradiation. The effect of the irradiation dose (25 kGy) exposure, at low temperature, on the formulation was evaluated. The sterilization procedure employed did not alter the physicochemical characteristics of the formulation. Dissolution profiles of formulations behaved similarly and overlapped (f(2) = 87.23, f(1) = 4.2) before and after sterilization. Size Exclusion Chromatography (SEC) revealed no significant changes in the polymer molecular weight. Additionally, a stability study of the sterilized formulation was carried out using microsphere storage conditions of VC in a vacuum desiccator for 1 year. The results obtained after storing the sterilized microspheres show no significant alterations in the ibuprofen release rate (f(2) = 85.06, f(1) = 4.32) or in the molecular weight of the PLGA (12957 Da). The employment of low molecular weight PLGA polymers resulted as advantageous, due to the practical absence of degradation after gamma irradiation (25 kGy) exposure at low temperature.