Abstract

The miscibility of active pharmaceutical ingredients with excipients is an important aspect in pharmaceutical technology protocols. In this study, the differential scanning calorimetry (DSC) was used for Sulfamethazine-Urea (SI–U) and Sulfamethizole-Urea (SO–U) solid-liquid phase diagrams determination. Both sulfonamides form simple binary eutectics with Urea. The lack of new co-crystal phase formation was confirmed by inspection of the powder x-ray diffractometry (PXRD) and attenuated total reflectance-Fourier-transform infrared spectroscopy (FTIR-ATR) measurements of the co-grinded mixtures. Despite the limited solid-state miscibility, a quantum-chemical calculations along with post-quantum thermodynamic characteristics performed using Conductor-like Screening Model for Realistic Solvents (COSMO-RS), have shown very high affinity of Sulfamethazine and Sulfamethizole to Urea in the liquid phase. However, the most significant contributions to the overall stabilization and solvation comes from self-association of sulfa-drugs. Noteworthy, a different hydrogen patterns are responsible for SI and SO dimerization since in the former case a cyclic C₂²(8) synthon occurs while in the latter linear hydrogen bonding motif is observed. The phase diagrams were modelled using different approaches including λh-equation, NRTL and Wilson and the corresponding parameters values were determined via non-linear fitting procedure. It was found that λh-equation has the highest predictive potential leading to very accurate reproduction of experimental results.

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Authors (5)