Solid–Liquid Phase Equilibrium Solubility and Model Correlation of Difenidol Hydrochloride in 12 Neat Solvents from (278.15 to 323.15) K

In the study, the experiment solubility of difenidol hydrochloride was determined in 12 neat solvents [water, methanol, ethanol, n-propanol, n-butanol, 1-pentanol, N-methyl-2-pyrrolidone(NMP), N,N-dimethylformamide(DMF), N,N-dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), acetonitrile (MeCN), and acetic acid] at a temperature range from 278.15 to 323.15 K by a gravimetric method under 0.1 MPa. Results indicated that the experimental mole fraction solubility (10x) order of difenidol hydrochloride in 12 neat solvents at the temperature 298.15 K was: methanol(0.1771)>DMSO(0.1343)>NMP(0.0725)>acetic acid (0.0601)>DMF(0.0467)>DMA(0.0357)>ethanol (0.0336)>n-propanol (0.0255)>n-butanol (0.0137)≈water (0.0135)>1-pentanol (0.0098)>MeCN (0.0041), and solubility increased with the increase in temperature. Three models, including Modified Apelblat model, Van’ t Hoff model, and Yaws model, were applied to correlate the experimental data and analyze the solubility data of difenidol hydrochloride. Based on the principle of similar compatibility, the law of solubility and miscibility of difenidol hydrochloride in selected solvents was discussed according to Hansen solubility parameters (HSP) and solvent effect for predicting solubility behavior.