Piroxicam is a crystalline anti-inflammatory drug with very low solubility and dissolution rate in aqueous solutions. Experiments have been performed to enhance the drug dissolution rate by dispersing it into a poly(vinylpyrrolidone) (PVP) matrix using supercritical CO2. Various PVP/drug systems at different polymer molecular weights (PVP K-15, K-30, K-90) were tested to investigate the role of the polymer occurring during the supercritical treatment. The impregnated powders were analysed via X-ray diffraction and Fourier-transform infrared (FTIR) spectroscopy to determine the physical state of the drug and the molecular interactions among the components. Further experiments were conducted treating the pure components in supercritical CO2. In vitro release tests of the impregnated systems were also performed and compared with those of the physical mixtures with the same drug content. When the impregnation was conducted at 300 bar and 100 C, no drug crystals were detected in the samples with a piroxicam content below 13-15%. The in vitro release tests showed a huge increase in the kinetics of release with respect to those of the physical mixtures, only for the completely amorphous PVP K-15/piroxicam samples. When PVP at higher molecular weight was employed, no changes or even a reduction in the kinetics of release were observed. This could be ascribed to the occurrence of higher molecular interactions between the drug and long-chain polymers treated under supercritical atmosphere. (C) 2009 Elsevier B.V. All rights reserved.