Solubility of Cortisone and Hydrocortisone in Supercritical Carbon Dioxide and Ethanol

Cortisone and hydrocortisone are poorly water-soluble corticosteroids widely used to treat many inflammatory and immune diseases. In the prospect of employing them in pharmaceutical applications or analytical techniques involving cosolvent-modified supercritical fluids, their solubility has been determined, for the first time, in a mixture of supercritical CO2 and 2, 3, or 4 mol % of ethanol, at 318.15, 328.15, 348.15, and 373.15 K, and in the pressure range of 13-27 MPa. Tests were conducted in a semi-flow laboratory apparatus, and results were fitted with the most popular density-based correlations reported in the literature for ternary systems. Even though the two drugs exhibit similar molecular structures, the solubility of cortisone in the ethanol-scCO2 mixtures is on average 3.5 times higher than that of hydrocortisone. This is congruent with the fact that the solubility of cortisone in pure ethanol is higher. The seven-parameter Reddy-Madras model (adjusted absolute average percent deviation (AARD%) = 8.8%) proved to be the best correlating one for cortisone while the six-parameter Garlapati-Madras approach (AARD% = 11.6%) provided the best fitting for hydrocortisone. The reliability of the experimental results was also confirmed by the positive response to the Mendez-Santiago-Teja self-consistency test.