Continuously Substituted Solid Solutions of Organic Co-Crystals

Solid solutions of isonicotinamide 2:[fumaric acid ( x ) succinic acid (1− x ) ] ( IN 2:[FA x SA (1− x ) ] 1 ) co-crystals were prepared. The system is anchored by two isostructural bimolecular co-crystals with compositions IN 2 SA 1 and IN 2 FA 1, respectively. The IN 2:[FA x SA (1− x ) ] 1 solid solutions of the co-crystals were formed using both solid-state grinding and solution crystallization. The solid solutions were found to be distinct from physical mixtures of IN 2 SA 1 and IN 2 FA 1 by analysis using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). DSC analysis of the solid solutions showed a linear interpolation of the melting point between the binary co-crystals whereas mixtures of the two separate co-crystals showed melting of the individual phases. PXRD was consistent with linear volume expansion of the lattice parameters without a concomitant change in the full width at half-maximum for the diffraction peaks for the solid solutions, but peak broadening and bimodality were observed for physical mixtures. Both techniques provided independent evidence that the solid solutions were a single phase and not physical mixtures of the two binary co-crystals.