High-pressure solubility of naproxen, nicotinamide and their mixture in acetone with supercritical CO2 as an anti-solvent

In this work, a new setup was designed in order to measure solubility of several solids in a sub or supercritical {CO2–solvent} mixture. The equipment is suitable to operate at temperatures ranging from 293 K to 333K and pressures up to 20 MPa. An analytical method was used, based on a variable-volume cell with sampling of fluid phase for HPLC analysis. Solubility of naproxen (NPX) and nicotinamide (NCTA) and their mixture in {acetone + supercritical CO2} systems were measured at two temperatures (298.15 and 310.65 K) and at 10 MPa over all range of CO2 compositions. CO2 acts as an anti-solvent for both solutes. For a quaternary mixture with an initial NPX:NCTA molar ratio of 2:1, the addition of CO2 induced the formation of cocrystal with a 2:1 stoichiometry. The solubility of NPX and NCTA decreased compared to the ternary systems. The solubility of NPX and NCTA increased with temperature.