Naproxen co-crystals with pyridinecarboxamide isomers

Abstract

A screening of naproxen cocrystals with coformers picolinamide, nicotinamide, isonicotinamide, and pyrazinamide is performed by the Kofler contact method and mechanochemistry. The solids obtained by mechanochemistry are characterized by differential scanning calorimetry, DSC, polarized light thermomicroscopy, PLTM, infrared spectroscopy, FTIR, and X-ray powder diffraction, XRPD. No cocrystal could be prepared under the experimental conditions investigated between naproxen and pyrazinamide, which bears two aromatic nitrogen atoms, ortho and meta to the amide group. For the o-, m-, and p-pyridinecarboxamide isomers, regardless of the aromatic nitrogen position, the coformer interacts with naproxen to give rise to new cocrystals: naproxen:picolinamide, naproxen2:nicotinamide, and naproxen:isonicotinamide. A supramolecular acid:aromatic nitrogen heterosynthon is found in all these cocrystals. The structure of the new naproxen:isonicotinamide compound was solved by single-crystal X-ray diffraction, SXD. As nicotinamide has FDA/GRAS status the naproxen:nicotinamide (2:1) cocrystal is of special relevance.