Experimental Study and Thermodynamic Modeling of Mesalamine and Azathioprine Solubility in Some Choline Chloride-Based Deep Eutectic Solvents
Tahereh Amini, Ali Haghtalab, Jaber Yousefi Seyf
Abstract
The present study attempted to measure the solubility of mesalamine and azathioprine in the aqueous solution of some deep eutectic solvents (DESs) at various DES weight fractions (0–1) over the temperature range of 283.15–323.15 K. We prepared the DESs by combining choline chloride (ChCl, hydrogen bond acceptor, HBA) and ethylene glycol (EG) and 1,2-propanediol (PD) (hydrogen bond donors, HBDs) with molar ratios of 1:2 and 1:3, respectively. The results indicate that the solubility is significantly increased up to 30-fold for mesalamine and 75-fold for azathioprine compared to water. Besides, the solubility of both pharmaceuticals is enhanced by increasing the temperature and weight fraction of DESs. Also, DES1 (ChCl + EG) shows higher solubility for mesalamine than DES2 (ChCl + PD), which is the opposite for azathioprine. The experimental solubility data were accurately correlated using the local composition models such as Wilson, nonrandom two-liquid theory (NRTL), and universal quasi-chemical (UNIQUAC). On the other hand, we applied the nonrandom two-liquid-segment activity coefficient (NRTL-SAC) and universal quasi-chemical segment activity coefficient (UNIQUAC-SAC) models to correlate and predict the solubility of the mesalamine and azathioprine in DES1 and DES2. In addition, the calculated values of the thermodynamic functions of dissolution reveal that in the dissolution process of both drugs, enthalpy is the primary contribution term to the standard Gibbs free energy.