Solid-liquid phase equilibrium, Hansen solubility parameters and thermodynamic behavior of Arbidol hydrochloride monohydrate in eleven mono-solvents

Abstract

The experimental mole-fraction solubility of Arbidol hydrochloride monohydrate (AHM) in eleven mono-solvents (water, methanol, ethanol, n-propanol, isopropanol, n-butanol, N,N-Dimethylformamide (DMF), n-Methyl-2-pyrrolidone (NMP), tetrahydrofuran (THF), acetone and ethyl acetate) at varied temperatures (from 293.15 K to 333.15 K at 5 K intervals) was determined under an atmosphere pressure of 0.101 MPa, which indicated that the solubility of AHM increases with the temperature arising. Furthermore, the solubility sequence of AHM at 298.15 K is: methanol (0.04422) > NMP (0.03516) > DMF (0.02437) > ethanol (0.01161) > n-propanol (0.006280) > n-butanol (0.004411) > isopropanol (0.001611) > THF (0.0004917) > acetone (0.0002516) > ethyl acetate (0.0001007) > water (0.00007344). The solubility behavior and the solute–solventinteraction of AHM in each selected mono-solvent had been explored by the Hansen solubility parameters (HSPs) and solvents polarity. Based on linear solvation energy relationships concept, the KAT-LSER model was applied to investigate the solvent effects. Experimental solubility of AHM was modelled by using four well-known SLE models, namely two empirical models (modified Apelblat model and λh model) and two activity coefficient models (NRTL model and UNIQUAC model), which indicated that four chosen SLE models can all give a satisfactory correlation solubility of AHM with the measured solubility data, while the modified Apelblat model shows the best correlation with experimental data in all investigated mono-solvents. In addition, the solution thermodynamic properties (ΔdisGo, ΔdisHo and ΔdisSo) of AHM in the selected mono-solvents were calculated by van’t Hoff equation. The ascending order of ΔdisGo is exactly in the reverse order of the molar solubility of AHM, implying less the value of ΔdisGo, more soluble in that solvent. The minimum ΔdisHo and ΔdisSo were found to be 16.04 kJ∙mol−1 in NMP and 25.83 J∙K−1∙mol−1 in NMP, respectively, while the minimum value of ζH is 60%, indicating that the dissolution process of AHM in the measured mono-solvents was endothermic and entropy-driven.