Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO(2)) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused drug were evaluated together with the impregnated drug stability. The composition of the obtained systems was characterized by I H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the drug over a long period of time. (C) 2008 Elsevier B.V. All rights reserved.