Supercritical carbon dioxide (sc-CO2) was used to impregnate indomethacin (a non-steroidal anti-inflammatory drug) into chitosan thermosets for the preparation of controlled release formulations. The products were analyzed by a range of methods including powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effects of the experimental temperature and pressure of the sc-CO2 on the thermal behavior of chitosan-indomethacin drug composites (DCs) was investigated via differential scanning calorimeter (DSC). The interaction of chitosan and indomethacin after impregnation was then studied by Fourier transform infrared (FTIR) and Raman spectroscopy, respectively. Our results suggest that the supercritical fluid impregnation process results in indomethacin being amorphously dispersed within the chitosan matrix. FTIR data suggest that the aliphatic carbonyl group of indomethacin interacts with the NH2 group of the chitosan backbone. In vitro dissolution studies (via UV-vis spectroscopy) reveal that the dissolution rate of indomethacin substantially increases after processing in sc-CO2, particularly, under the experimental conditions 20.7 MPa and 70 °C. © 2006 Elsevier B.V. All rights reserved.