The determination of the drug dispersion state in microspheres prepared by the solvent evaporation method is essential to foresee the stability of the particles and the drug release behavior. The present work deals with ibuprofen-loaded ethylcellulose microspheres, that are characterized by a lower drug melting point than the polymer glass transition temperature. Although annealing experiments were not possible, the study has evidenced the presence of a metastable molecular dispersion for intermediate loadings, coexisting with a solid solution and a crystalline dispersion of the drug in the polymer matrix. In addition, differential scanning calorimetry helped to distinguish between surface and inner ibuprofen crystals, which interact differently with the polymer matrix and therefore have different melting points.