Solubility Behavior of Meglumine Form I in 12 Pure Solvents: Experimental Measurements, Thermodynamic Modeling, And Solvation Mechanism Analysis

The solubility of meglumine Form I was systematically determined in 12 pure solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, ethyl formate, methyl acetate, ethyl acetate, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide (DMF), and acetonitrile) using a gravimetric method over the temperature range of 288.15 to 328.15 K. Solubility increased with temperature in all systems, with DMF exhibiting the highest solubility and acetonitrile the lowest. Three thermodynamic models (the modified Apelblat, λh, and van’t Hoff) were employed to correlate the solubility data, among which the modified Apelblat model provided the best fit. The solubility behavior of meglumine Form I was further analyzed using Hirshfeld surface analysis, the Kamlet–Abboud–Taft linear solvation energy relationship (KAT-LSER) model. The results demonstrate that the solvent’s hydrogen-bond acceptor capability is the key determinant of solubility, as it generates sufficiently strong solute–solvent interactions to overcome the robust hydrogen-bond network within the crystal lattice. These findings provide essential thermodynamic data and mechanistic insights for the optimization of meglumine crystallization and formulation processes.