Impregnation of PVP microparticles with ketoprofen in the presence of supercritical CO2

The aim of the work is to enhance the oral bioavailability of ketoprofen by inserting it into a water-soluble polymer, poly(vinylpyrrolidone) (PVP) K30, using supercritical carbon dioxide as the impregnating solvent. Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) characterized by low solubility and a low dissolution rate in the gastrointestinal tract, PVP is a biocompatible water-soluble polymer with a fast dissolution rate and supercritical CO2 is a clean non-toxic solvent that is able to plasticize amorphous polymers.The physical state of the drug in the polymer has been investigated through Fourier Transform Infrared (FTIR) spectroscopy and powder X-ray diffraction (PXRD) and it has been compared with that of the PVP-ketoprofen physical mixtures. The results of the analyses show that an amorphous solid dispersion of the drug in the polymer can be obtained even at high concentrations.Impregnated polymer powders were compressed into tablets and the release kinetics was evaluated to study the drug dissolution rate. The release curves of the physical mixtures, with the same drug content, were also measured and compared with those of the impregnated polymer tablets. The results show that the release mechanism depends on the tablet composition and that it is necessary to work with not too high a drug content to obtain a large enhancement of the dissolution kinetics.