Continuously Substituted Solid Solutions of Organic Co-Crystals

Abstract

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.

Characterization and Quality Control of Pharmaceutical Cocrystals

“…2) Although most cocrystals contain uniform API and coformer distributions, some solids (e.g., solid solutions) show variations in component ratios depending on positions. 25) Some new forms of multi-component crystals have been developed for pharmaceutical applications (e.g., BioMOFs); these materials are beyond the scope of this review. 26) Detailed crystal structures may provide a theoretical basis for the quality control of pharmaceutical cocrystals, which is achieved by the powerful single-crystal XRD technique.…”

Formation of isostructural solid solutions in 2,6-disubstitutedN-phenylformamides andN-phenylthioamides

“…An additional crystal engineering strategy to altering physiochemical properties is to prepare solid solutions (Hollingsworth, 2002), which are defined as a non-stoichiometric multi-component complex, compared with co-crystals, which have a definite stoichiometric ratio (Lemmerer & Fernandes, 2012;Aakerö y & Salmon, 2005;Bond, 2007;Dunitz, 2003). Recently, work has been published that refers to both solid solutions and co-crystals contained in one crystalline entity (Chen et al, 2010;Bučar et al, 2012;Oliveira et al, 2008), although for the purposes of this report we will restrict ourselves to describing our complexes as solid solutions. There are many reports on the synthesis of new materials using co-crystallization methods and in particular taking advantage of the hydrogen bonds in the starting materials to derive specific motifs and architectures and can influence the aggregation of different molecules in crystals, sometimes with predictable connectivity patterns (Etter, 1985;Etter et al, 1986;Panunto et al, 1987;Etter & Panunto, 1988;Etter & Baures, 1988;Aakerö y et al, , 2006.…”

Crystal structure of succinic acid — 4-((pyridin-4-ylmethyl)sulfanylpyridine (1/1), C15H16N2O4S

“…They belong to an interdisciplinary eld of research that deals with the understanding of non-covalent interactions [2][3][4]. Interactions between carboxylic acids and pyridyl derivates are extensively used to develop supramolecular assemblies [5][6][7][8]. In the asymmetry unit of the title structure, there are one 4-((pyridin-4-ylmethyl)sulfanyl)pyridine and one succinic acid (Figure).…”