The present study explores the possibility to synthetize, using supercritical fluid, single crystal of co-crystal formed by mefenamic acid as active pharmaceutical ingredient and nicotinamide as a co-former. The growth of single crystals is important for the determination of co-crystal structure and in particular, for the ones whose unit cells contain a large number of atoms, it becomes crucial. For this purpose, we analyzed the effect of temperature, solid mixture composition and time duration of the co-crystallization process on the synthetized solid. The structure of the latter was determined using single-crystal X-ray diffraction while the composition of fine powders and the intermolecular interactions involved in their synthesis were analyzed using powder X-ray diffraction and diffuse reflectance infrared Fourier transform spectroscopy respectively. Our results show that the single crystal of mefenamic acid and nicotinamide co-crystal is synthetized for the first time in supercritical CO2 at 90 °C, 193 bars and a time duration of three weeks.