Benzodiazepines co-crystals screening using FTIR and Raman spectroscopy supported by differential scanning...

Co-crystals, which are defined as "solids that are crystalline materials composed of two or more molecules in the same crystal lattice" have recently been the focus of increased interest in the pharmaceutical industry since co-crystallization can improve unfavorable physicochemical properties of active pharmaceutical ingredients. Thus, the quest for new co-crystal screening methods has become an issue of importance. The aim of this work was, therefore, to show to what extent expanded methodology based on FTIR and Raman spectroscopy supported by the DSC method can be used as a reliable tool to screen co-crystallization. Because co-crystals of benzodiazepines had not yet been obtained, a set of 72 binary mixtures composed of eight 1,4-benzodiazepine derivatives and nine coformers were used as model substances. Potential co-crystals were prepared in solid-state by liquid-assisted grinding procedure. The characteristic FTIR and Raman bands which reflect hydrogen bond formation between benzodiazepine and coformer were used as proof of co-crystal creation. DSC was used as a supporting tool to reflect the phase transitions which occur during co-crystallization. As a result of the study, four potential co-crystals can be selected: lorazepam with nicotinamide, chlordiazepoxide with p-aminobenzoic and saccharin, and estazolam with fumaric acid. The detailed spectral and thermal characteristics of these systems are presented in this work. Thus, the proposed methodology of co-crystal screening based on FTIR and Raman data supported by the DSC examination of phase transitions facilitates the screening and detection of benzodiazepine co-crystal prepared by short time components ground with a slight additional volume of solvent.