Research subject: This study investigates the solubility of mesalazine, an important drug for the treatment of inflammatory bowel diseases, in novel solvent systems based on deep eutectic solvents (DESs). These systems consist of betaine (Bet) as a hydrogen bond acceptor (HBA) and acetic acid (AA) as a hydrogen bond donor (HBD), mixed with water. The significance of this research lies in two main aspects: first, understanding the solubility behavior of mesalazine in environments simulating physiological conditions, which affects the drug’s bioavailability; and second, providing practical data for designing and optimizing industrial processes such as crystallization and extraction of this drug.
Research approach: The solubility of mesalazine was measured in the temperature range of 293.15 to 313.15 K and at various DES mass fractions (0.0, 0.2, 0.4, 0.6, 0.8, and 1.0) in water using the shake-flask method. The effect of varying the molar ratio of HBD on solubility was also examined, and three DES types with Bet/AA ratios of 1:2 (DES1), 1:3 (DES2), and 1:5 (DES3) were prepared.
Main results: The results showed that increasing the DES mass fraction at a constant temperature significantly enhanced the solubility of mesalazine. Likewise, increasing the temperature at a fixed DES mass fraction led to higher drug solubility in the solvent mixture. The effect of the HBD molar ratio revealed that the highest solubility occurred in DES3 (Bet/AA (1:5)), highlighting the significant role of enhanced hydrogen bonding in improving solubility. Thermodynamic analysis based on the Van’t Hoff and Gibbs equations indicated that the dissolution of mesalazine in water and DESs is an endothermic process, accompanied by positive enthalpy and entropy values. These findings can serve as a valuable basis for developing novel solvent systems and optimizing industrial processes related to mesalazine and other poorly water-soluble drugs.