Liquid–Liquid Phase Separation and Solubility of Isomalt in Five Binary Solvents: Hansen Solubility Parameters, Molecular Dynamics Simulations and Thermodynamic Properties at 283.15–323.15 K

The mole fraction solubility of Isomalt in five binary solvent systems (water + methanol, ethanol, 1-propanol, isopropanol, tert-butanol) was determined via the gravimetric method at atmospheric pressure and 283.15–323.15 K. Solubility increased with rising temperature and water molar fraction, following the order: water + methanol > water + ethanol > water +1-propanol > water + isopropanol > water + tert-butanol, with solubility curve intersections indicating varying temperature sensitivities. Liquid–liquid phase separation occurred in water +1-propanol/isopropanol/tert-butanol at high water mole fractions. Four thermodynamic models (modified Apelblat, van’t Hoff, λh, Jouyban–Acree van’t Hoff) yielded excellent fits (ARD < 10%, RMSD < 0.1%), with the modified Apelblat model being best correlation. Hansen solubility parameter analysis showed solubility was governed by hydrogen-bonding parameters (Δδh) and total solubility parameter (Δδ̅). Hirshfeld surface analysis (HS) and radial distribution function (RDF) simulations confirmed hydrogen bonding as the dominant solute–solvent/solvent–solvent interaction. Thermodynamic calculations based on the van’t Hoff equation confirmed that the dissolution process is endothermic and entropy-driven. These findings provide comprehensive solubility data and mechanistic insights, supporting future research and applications of isomalt in alcoholic solutions.