Studies on the solid–liquid equilibria and intermolecular interactions Urea binary mixtures with Sulfanilamide and Sulfacetamide

Abstract

The binary phase diagrams of Sulfanilamide-Urea (SN-U) and Sulfacetamide-Urea (SC-U) were measured using differential scanning calorimetry technique (DSC). Both examined mixtures were found to form simple binary eutectics. The limited miscibility in the solid state observed by DSC, proving inability of co-crystallization in new multi-molecular form, was also confirmed using PXRD and FTIR-ATR measurements of solid dispersions obtained via liquid assisted co-grinding. The lack of intermolecular complex formation in the crystals does not imply the lack of interactions in the liquid state. Detailed characteristics of potential homo- and hetero-molecular pairs were offered using ab initio and the first principle quantum chemistry computations. The obtained results happened to be strongly dependent on the applied level of theory. The importance of including the zero point energy contributions and electron correlation corrections was emphasized. It was found that the mole fraction of hetero-complexes with urea is the highest among all other constituents of studied systems at their eutectic points. Finally, the importance of intermolecular interaction leading to complexes formation in the liquid state at saturated position was documented by computed values of solvation Gibbs free energy. Based on computed trends it was inferred that the eutectic mixtures can be interpreted as such equilibria for which mutual solvation of all components is maximized.