Continuously Substituted Solid Solutions of Organic Co-Crystals

Abstract

Solid solutions of isonicotinamide2:[fumaric acid(x)succinic acid(1−x)] (IN2:[FAxSA(1−x)]1) co-crystals were prepared. The system is anchored by two isostructural bimolecular co-crystals with compositions IN2SA1 and IN2FA1, respectively. The IN2:[FAxSA(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 IN2SA1 and IN2FA1 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.