Solubility and thermodynamics of probenecid-4,4′-azopyridine cocrystal in pure and binary solvents

Abstract

Cocrystals of probenecid-4,4′-azopyridine (2:1) form I were first prepared by cooling cocrystallization method and characterized by scanning electron microscope (SEM), optical microscopy, powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FT-IR). The solubility of cocrystal form I in six pure solvents and two binary solvents with temperature from 273.15 K to 313.15 K was measured by using a gravimetric method. Solubility of cocrystals increases when the temperature rises in pure and both of binary solvents. In pure solvents, the solubility of cocrystals form I from largest to smallest follows the order acetone > ethyl acetate > ethanol ≈ 1-propanol ≈ 2-propanol > acetonitrile. The modified Apelblat equation, λh equation and NRTL model were used to the correlate solubility data in pure solvents and those three models plus CNIBS/Redlich-Kister model and modified Jouyban-Acree model were chosen to correlate the solubility data in two binary solvents. All models provide great correlation and accuracy. Besides, apparent dissolution enthalpy, entropy and Gibbs energy were obtained through NRTL model and the result shows that in six pure and two binary solvents, the process of dissolution of form I of probenecid-4,4′-azopyridine cocrystals is spontaneous, endothermic and driven by entropy.