Solubility behaviors of ibuprofen and naproxen drugs in liquid “CO2–organic solvent” mixtures

The “vanishing point” method was used for measuring the solubility of the two non-steroidal anti-inflammatory drugs ibuprofen and naproxen in CO2–expanded ethanol and CO2–expanded acetone at 10 MPa and 298 K. The solubility behavior of both drugs in ethanol/CO2 mixtures is quite similar, where the CO2 acts together with ethanol as co-solvents in a wide range of CO2 molar fractions. However, these two drugs exhibit a different solubility behavior in acetone/CO2 mixtures since the CO2 acts as a co-solvent in the system ibuprofen + acetone + CO2, whereas exhibits a strong anti-solvent character, from low CO2 molar fractions, in the system naproxen + acetone + CO2. The obtained data reflect that naproxen solubility behavior is strongly dependent on the protic or aprotic nature of the organic solvent whereas for ibuprofen this solvent characteristic seems to be less important. The measurement of the solubility behavior of such drugs has permitted to choose the best precipitation method using CO2–expanded solvents for its processing as micro-particulate solids.