Experimental Investigation and PC-SAFT Modeling of Etodolac Solubility in Deep Eutectic Solvents and Aqueous Solutions

The measurement and modeling of drug solubility are crucial for guiding solvent selection in the pharmaceutical formulation development process. Here, the solubility of etodolac was determined in six deep eutectic solvents (DES1–DES6) based on choline chloride as the hydrogen bond acceptor combined with different hydrogen bond donors (polyols and carboxylic acids) and their corresponding hydrogen bond donor (HBD1–HBD6) aqueous solutions, under conditions of 293.15–333.15 K and 101.3 kPa. All HBD and DES systems exhibited a significant solubilizing effect. Among them, the propionic acid system showed the most pronounced enhancement in the solubility of etodolac. Powder X-ray diffraction (PXRD) results confirmed that the crystal form of etodolac remained stable throughout the experiments, ensuring the reliability of the solubility data. The solubility data were further modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state, combined with solid–liquid equilibrium theory. The results showed good agreement between the calculated and experimental values, with most ARD values below 10%, and the minimum value reaching only 0.564%, indicating that the PC-SAFT model reliably predicts the solubility behavior of etodolac in various solvent systems and serves as a powerful theoretical tool for drug research and development.