Stability, solubility and thermodynamic properties of dimorphs of furosemide-4,4′-bipyridine cocrystals in organic solvents

Abstract

In this work, pure form I and form II of furosemide-4,4′-bipyridine (FS-4BPY) 2:1 cocrystals were prepared. Both polymorphs were characterized by optical microscopy, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The relative stability of the two forms was estimated from their solubility data in 2-propanol by the gravimetric method. Moreover, the thermodynamically stable form with lower solubility, form II, was further investigated in different pure and binary solvents from 293.15 K to 333.15 K under atmospheric pressure. In pure solvent system, the solubilities of forms II cocrystals increase with rising temperature and follow the order of acetone > ethanol > 1-propanol ≈ 1-butanol > 2-propanol > acetonitrile. In 2-propanol–water binary solvent system, the co-solvency phenomenon was observed and the maximum solubility of form II is higher than that in pure solvents. The experimental solubility data were correlated by the modified Apelblat model, the CNIBS/R–K model, the Jouyban–Acree model and the NRTL model, and all models give satisfactory correlations. Finally, the apparent dissolution thermodynamic properties, including the dissolution Gibbs energy, the dissolution enthalpy and the dissolution entropy, were calculated based on the NRTL model. The results indicate that the dissolution processes of form I and form II of FS-4BPY cocrystals in selected solvents are all spontaneous, endothermic, and entropy-driven.