Solubility Behavior and Data Correlation of Phenytoin in 12 Pure Single-Solvent Systems at 283.15–323.15 K

The solubility of phenytoin in 12 pure organic solvents (methyl acetate, 2-butanol, methanol, ethanol, 1-butanol, n -propanol, 1-pentanol, ethyl acetate, isopropanol, butyl acetate, 2-methyl-1-propanol, and acetonitrile) was determined over the temperature range of 283.15–323.15 K. The experimental data were correlated by using the modified Apelblat model and the Yaws model. The solubility of phenytoin increased with the temperature. Among the two fitted models, the Yaws model provided superior fitting performance, yielding a lower average ARD of 1.17%, whereas the modified Apelblat model gave a slightly higher average ARD of 1.24%. Hirshfeld surface (HS) analysis was also employed to investigate molecular interactions, which revealed strong hydrogen-bonding interactions between phenytoin and solvent molecules. Additionally, the solubility behavior in different solvents was analyzed in terms of E T (30), hydrogen-bond donor and acceptor parameters, and cohesive energy density. The results indicate that hydrogen bonding is the dominant factor governing the solubility behavior of phenytoin. These findings provide useful references for the purification, crystallization, and industrial application of phenytoin and its analogues.