Assessment of Solubility of Ketoprofen and Vanillic Acid in Supercritical CO2under Dynamic Conditions

The use of supercritical fluids, and in particular supercritical carbon dioxide (SC-CO2), can be foreseen in a wide range of techniques and processes within pharmaceutical sciences. When dealing with both drugs and formulation adjuvants, the determination of the relevant solubilities in SC-CO2 represents a mandatory prerequisite, underlying the development of industrial scale operations. The aim of this work concerned the experimental determination of the solubility in SC-CO2 of vanillic acid and ketoprofen by means of an easy-to-use plant designed and assembled to operate in dynamic conditions. Its reliability was preliminary checked by comparing solubility data obtained for salicylic acid and naphthalene with literature ones. Solubility measurements for ketoprofen and vanillic acid were carried out at 313 and 328 K in the 9-25 MPa pressure range. Crossover pressures of 16 MPa and 15 MPa were found for ketoprofen and vanillic acid, respectively. The solubility data were worked out according to a thermodynamic approach, which relies on the Peng-Robinson equation of state.