The objective of this study was the development and optimisation of biodegradable PLGA microspheres loaded with ibuprofen destined for intraarticular administration. The formulation was designed to provide "in vitro" therapeutic concentrations of ibuprofen (8 microg/ml) for as long as possible. The solvent evaporation method based on an o/w emulsion was used to form the microparticles. The polymer used was Poly (D,L-lactide-co-glicolide) 50:50 (PLGA), of different molecular weights (Mw) (34,000, 48,000 and 80,000 Da). In order to get a more controlled release rate of ibuprofen, a biodegradable oil, Labrafil M1944CS, polyethylene glycol 300 derivative, was used as an additive. The formulation was optimised by means of an experimental design, 2(3) being the variables: X(1) = PLGA Mw; X(2) = initial ibuprofen:polymer ratio; X(3) = percentage of Labrafil. The theoretical profile yielding in vitro "therapeutic" concentrations of ibuprofen (8 microg/ml) was calculated. The experimental profiles obtained for the formulations tested were compared with the theoretical one by means of the difference factor (f(1)). In all cases, the addition of Labrafil lowered the initial ibuprofen burst, prolonging the release rate of the drug from 24 h (without additive) up to 8 days incorporating the oil. The microspheres made from the PLGA (Mw = 34,000 Da) with Labrafil addition (10%) and ibuprofen:polymer (15%) ratio (formulation 1) yielded the most suitable release profiles. Forty milligram of the selected formulation (formulation 1), was sufficient to provide in vitro "therapeutic" concentrations of ibuprofen (8 microg/ml) up to 8 days. Labrafil modulates the release rate of donor-acceptor substances such as ibuprofen.