Multicomponent adducts such as cocrystals and eutectics have become an integral part of the pharmaceutical industry since the application potential of such products is imminent in drug design and fabrication. Cocrystallization of metronidazole, an antibiotic antiprotozoal drug, belonging to the family of nitro-imidazole, with benzoic acid and mono-, di-, tri-, hydroxybenzoic acids results in multicomponent adducts with better physicochemical properties than the drug. Cocrystallization experiments using liquid assisted grinding (LAG), melt cool, and routine solvent evaporation yielded eutectics except for the combinations 3,5-dihydroxy and 3,4,5-trihydroxybenzoic acids, which produce cocrystals. The products have been characterized and analyzed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In particular, the structures of the cocrystals were determined using single crystal X-ray diffraction, whereas those of the eutectics were identified based on PXRD, DSC, and binary phase diagram construction. Using well-known thermal inkjet printing (TIJP), organic solutions of metronidazole and substituted hydroxybenzoic acids were injected into a cartridge and printed onto the template via a jet dispensing mechanism by varying the drug–coformer stoichiometric ratio to generate the cocrystals and eutectics of the adducts in quick time. The products formed from inkjet printing show excellent consistency in the particle size distribution and can be easily subjected to scaling up in industry compared to those prepared using the conventional cocrystallization techniques such as slurry grinding, rotavapor, and routine solution evaporation, which are time-consuming and produce varying particle sizes, which is a hindrance to product development and scaling during mass production.

Benzoic acid–monofluorobenzoic acid combinations are known to form solid solutions, whereas benzoic acid–pentafluorobenzoic acid system forms a cocrystal. To decipher the gradation from solid solution to cocrystal between these extremes, we executed the cocrystallization of benzoic acid with several of its poly-fluoro (di-, tri-, and tetra-) substituents. The fluorine atom, with its sheer geometric position and intermolecular (hydrogen and halogen) bonding ability, is found to steer the transformation from a solid solution to a cocrystal in this family of compounds. We found, among others, a novel crystal entity in the benzoic acid–3,4,5-trifluorobenzoic acid combination that shows characteristics of both a solid solution (a single disordered molecule in the crystallographic asymmetric unit) and a cocrystal (a distinct crystal structure as compared with the parent compounds). This solid solution-cum-cocrystal therefore acts a connecting link in the evolution of cocrystals from solid solutions in benzoic acid–fluorobenzoic acid systems. In addition, the cocrystallization of benzoic acid with 2,6-difluorobenzoic acid and 2,4,6-trifluorobenzoic acid resulted in eutectics, which appears to be due to the supramolecular incompatibility invoked by out-of-plane carboxylic acid in the latter compounds.

The search for multifunctional organic compounds that display technologically important properties has been pursued in recent years. Here we report the synthesis and structure of a series of single-component N-benzylideneaniline analogues 4-(4-(4-nitrobenzylideneamino)­benzyl)­oxazolidin-2-one (NBOA), 4-(4-(4-chlorobenzylideneamino)­benzyl)­oxa-zolidin-2-one (CBOA), and 4-(4-(4-hydroxybenzy-lideneamino)­benzyl)­oxazolidin-2-one (HBOA). The dynamic disorder observed in the structure of NBOA is investigated using variable temperature single crystal X-ray diffraction. All three compounds display second harmonic generation, well-defined PE loops with hysteresis at room temperature typical of ferroelectric materials, and significant dielectric behavior with tolerance toward high electric fields.

Cocrystals and solid solutions are different yet related crystalline multi-component adducts known to modulate the physicochemical properties of various chemical substances, thus finding applications in pharmaceutical and materials science. Solid solutions are more candid to design than cocrystals as it is well-established that a solid solution is formed by substitutional incorporation of a substance in the crystal lattice of another substance based on the isomorphous and/or isostructural relationships. Thus, a solid solution retains homomeric interactions and adopts the crystal structure of one of the parent substances. In contrast, a cocrystal can manifest for a combination wherein heteromeric interactions outweigh homomeric interactions of individual components. Since the heteromeric interactions are structure-directing, a cocrystal has unique crystal packing and can be readily characterized by X-ray diffraction techniques. Cocrystallization behaviour among various benzoic acid-fluorobenzoic acid combinations is explored to evaluate the propensity of preferred adduct in these combinations. It is reported that benzoic acid-4-fluorobenzoic acid combination forms a solid solutions whereas benzoic acid-pentafluorobenzoic acid combination forms a cocrystal. In the background of these extremes, a systematic cocrystallization study has been undertaken to determine the effect of number of fluorine atoms in the metamorphosis of homomeric interactions to heteromeric ones for combinations containing di-, tri-and tetra-fluorobenzoic acids. The gradation from solid solution (BA-monofluoro BA) to cocrystal (BA-pentafluoro BA) with eutectic phases in certain di-and tri-fluorobenzoic acid combinations is discussed. The study involves crystal structure determination, powder diffraction and thermal analysis and thus allows for deriving general guidelines to generate desired crystal forms by fine tuning hetero-and homomeric interactions.