SOLUBILITY OF NAPROXEN IN SUPERCRITICAL CARBON-DIOXIDE WITH AND WITHOUT COSOLVENTS

The solubility of naproxen ((S)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid) in supercritical CO2 was determined at 313.1, 323.1, and 333.1 K. The influence of six polar cosolvents, ethyl acetate, acetone, methanol, ethanol, 1-propanol, and 2-propanol, was studied at concentrations of 1.75, 3.5, and 5.25 mol %. The solubility enhancement with these cosolvents is considerable, and the cosolvent effect increases in the order ethyl acetate, acetone, methanol, ethanol, 2-propanol, 1-propanol. A nonlinear increase in solubility is observed with an increase in cosolvent concentration. The use of the Peng-Robinson and Soave-Redlich-Kwong equations of state to correlate these ternary systems requires the use of negative binary interaction parameters indicating strong interactions between naproxen and the cosolvents. The cosolvent effects cannot be explained by any one physical property of the cosolvents but appear to be influenced by hydrogen bonding ability as determined from solvatochromic parameters as well as the relative distance from the CO2-cosolvent binary critical point.