Solid-Liquid Phase Equilibrium and Dissolution Properties of Oxalyl Dihydrazide Form α in Pure Organic Solvents

Abstract

Oxalyl dihydrazide (ODH) is a polymorphic organic compound, and distinct ODH polymorphs possess disparate physicochemical properties, including melting point, solubility, and dissolution kinetics. Under atmospheric pressure, the dynamic method was applied to obtain solid–liquid phase equilibrium information on α-ODH within the temperature range of 293.15–353.15 K. Twelve pure solvents were selected for the tests, namely, water, ethanol, acetic acid, dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), N-ethyl-2-pyrrolidone (NEP), N,N-dimethylacetamide (DMAC), N,N-diethylformamide (DEF), N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), hexamethylphosphoramide (HMPA), and formamide. Experimental results indicated that the solubility of α-ODH monotonically increased with the increase in temperature in all tested solvents. Three thermodynamic models (van’t Hoff equation, Yaws model, and the modified Apelblat equation) were employed to correlate the measured solubility data. In addition, the dissolution thermodynamic properties (Gibbs free energy, entropy, and enthalpy) of α-ODH in the tested solvents were calculated based on the experimental solubility data and the van’t Hoff equation. Moreover, Hirshfeld surface analysis was implemented to characterize dominant intermolecular contacts inside the α-ODH crystal lattice. The acquired solubility data offers reliable fundamental support for industrial crystallization optimization of α-ODH.