Solubility of ethenzamide and 2-chloro-4-nitrobenzoic acid in supercritical carbon dioxide from experiments and thermodynamic models

The solubility of solid solutes in supercritical carbon dioxide (scCO₂) is critical for crystal engineering and pharmaceutical formulation. In this study, the solubility of ethenzamide and 2-chloro-4-nitrobenzoic acid in scCO₂ was measured for the first time using a high-pressure semi-flow apparatus at 308.2 K, 318.2 K, and 328.2 K over a pressure range of 10 MPa to 22 MPa. The solubility of ethenzamide ranged from 1.09 × 10⁻⁵ to 3.24 × 10⁻⁴, and that of 2-chloro-4-nitrobenzoic acid from 3.88 × 10⁻⁶ to 2.07 × 10⁻⁴ (in mole fraction). Four semi-empirical models [Chrastil, Bartle, Mendez-Santiago & Teja (MST), and Kumar & Johnston (K-J)] were used to correlate the experimental data, yielding average absolute relative deviations (AARD) of 2.17–7.10 % for ethenzamide and 4.00–5.99 % for 2-chloro-4-nitrobenzoic acid, confirming the reliability of the measured solubility data. The validated data were further used to evaluate three thermodynamic approaches based on the Peng–Robinson equation of state (PR EOS). Among them, PR+VDW and PR+MHV1+Wilson achieved AARD values of 4.92 % and 8.97 % for ethenzamide, and 3.81 % and 8.64 % for 2-chloro-4-nitrobenzoic acid, respectively. The PR EOS couple with the COSMO-SAC model, implemented via the MHV1 mixing rule, provided good solubility predictions (AARD values of 33.98 % for ethenzamide and 6.30 % for 2-chloro-4-nitrobenzoic acid) without the need for parameter fitting.