Rational Coformer Selection in the Development of 6-Propyl-2-thiouracil Pharmaceutical Cocrystals

Pharmaceutical multicomponent solids have proved to efficiently modulate the physicochemical properties of active pharmaceutical ingredients. In this context, polyphenols are interesting coformers for designing pharmaceutical cocrystals due to their wide safety profile and interesting antioxidant properties. The novel 6-propyl-2-thiouracil multicomponent solids have been obtained by mechanochemical synthesis and fully characterized by powder and single-crystal X-ray diffraction methods. The analysis of supramolecular synthons has been further performed with computational methods, with both results revealing a robust supramolecular organization influenced by the different positions of the hydroxyl groups within the polyphenolic coformers. All novel 6-propyl-2-thiouracil cocrystals show an enhanced solubility profile, but unfortunately, their thermodynamic stability in aqueous media is limited to 24 h.

Automated summary

Pharmaceutical multicomponent solids effectively modulate the physicochemical properties of active pharmaceutical ingredients. Polyphenols, with their wide safety profile and antioxidant properties, are interesting coformers for designing pharmaceutical cocrystals. Mechanochemical synthesis was used to obtain novel 6-propyl-2-thiouracil multicomponent solids, which were fully characterized using X-ray diffraction methods. Computational methods were also employed to analyze the supramolecular organization, revealing a robust structure influenced by the different positions of the hydroxyl groups in the polyphenolic coformers. These cocrystals show enhanced solubility but limited thermodynamic stability in aqueous media, lasting only 24 hours.