The solubility of N-acetyl-l-glutamic acid in 12 pure solvents was determined using the static gravimetric method at standard atmospheric pressure from 283.15 to 323.15 K. The solubility was positively correlated with temperature across all systems, reaching a maximum in methanol at 323.15 K and a minimum in propyl acetate at 283.15 K. Powder X-ray diffraction confirmed a polymorphic transformation exclusively upon testing in n-propanol. The dissolution behavior was systematically related to solvent properties, including polarity (ET(30)), cohesive energy density, and hydrogen-bonding interactions, which were further visualized via molecular electrostatic potential surfaces (MEPs). Experimental data were successfully correlated by using the modified Apelblat, Margules, and NRTL models, demonstrating excellent accuracy. Additionally, a comparative structural analysis with l-glutamic acid 5-methyl ester elucidated the macroscopic solubility differences based on specific solute–solvent interactions. Finally, the mixing thermodynamic properties derived from the NRTL model indicated that the dissolution is a thermodynamically favorable entropy-driven process. These comprehensive findings could provide essential fundamental data and mechanistic guidance for the crystallization design and pharmaceutical development of N-acetyl-l-glutamic acid.
Tang et al. (Sun,) studied this question.