Favipiravir-indomethacin interaction and its impact on their solid-state character

Favipiravir is an antiviral agent, a weak acid, and slightly soluble in water, while indomethacin is a weak basic compound and a poorly water-soluble anti-inflammatory drug. This study aimed to combine the two drugs as an eutectics mixture system to enhance their physicochemical properties. The study began with a phase diagram constructed from thermal analyses using electrothermal data, elaborated with differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier transform infrared (FTIR) spectroscopy, and electron microscopic observation. The mixture was then evaluated for its solubility characteristics. The unique profile of the phase diagram indicated a melting point lower than those of the starting materials, at 144 °C, observed at a 1:2 molar ratio of favipiravir–indomethacin. DSC also showed a single endothermic curve at the same temperature. Subsequently, the PXRD and FTIR data revealed no new physical or chemical phases, confirming a simple eutectic interaction between the antiviral and anti-inflammatory agents, which is rare in drug–drug interactions. However, the solubility tests showed significant improvement, particularly for indomethacin, which exhibited up to a 100-fold increase in solubility. The change in particle form and size was predicted as the mechanism responsible for the increased solubility, which was then confirmed by scanning electron microscopy (SEM). Imaging confirmed that favipiravir coats the surface of indomethacin, reducing interfacial tension. Smaller particle sizes are likely to increase surface area and solubility, potentially enhancing bioavailability and accelerating the onset of action. These findings support the development of a solid-state antiviral–anti-inflammatory drug combination.