The polymerization of 1-vinyl-2-pyrrolidone in supercritical carbon dioxide in the presence of ibuprofen as a model drug was investigated as a new one-pot process for the preparation of polymer-based drug delivery systems (DDSs). The composites were prepared at 65 degrees C and P = 31-42 MPa by changing the initial concentration of the drug and the concentration of a crosslinking agent and that of a hydrophobic comonomer. The effects of these parameters on the performances of the polymerization and on the in vitro release kinetics of ibuprofen were studied. In all the experiments, part of the drug was entrapped inside the polymer particles and dissolved more slowly with respect to the pure compound. Copolymerization with methyl methacrylate was the most effective route to obtain a DDS with sustained temporal release of the drug molecule. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7429-7446, 2008