Characterization of new cocrystals by raman spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and transmission raman spectroscopy

Cocrystals have been increasingly recognized as an attractive alternative delivery form for solids of drug products. In this work, salicylic acid was employed as a cocrystal former with the nicotinic acid, dl-phenylalanine, and 6-hydroxynicotinic acid (6HNA). Also, 3,4-dihydroxybenzoic acid with oxalic acid was studied. The cocrystals in all cases were prepared by slow evaporation from ethanol followed by characterization using Raman spectroscopy, powder X-ray diffraction, transmission Raman spectroscopy (TRS), and differential scanning calorimetry. Full understanding of the effects of formation on the vibrational modes of motion was obtained by the complete assignment of the spectra of the starting materials and of the cocrystal components. The results show that all the cocrystals, prepared in a 1:1 molar ratio, possess unique thermal, spectroscopic, and X-ray diffraction properties. Raman and TRS spectra showed that the vibrational modes of the cocrystal were different from those of the starting materials, suggesting that Raman spectroscopy and TRS are effective tools to evaluate cocrystal formation through interaction of their components. In addition, we have used a synthetic standard containing a 1:1:1 mixture of KNO 3 and raw material for which each sample was analyzed at seven random positions, with each point sampled twice. We have done the same with all cocrystals (1:1 KNO 3 and cocrystal), the ratios confirming that the cocrystal components (were in a 1:1 molar ratio). © 2010 American Chemical Society

Identification of a new co-crystal of salicylic acid and benzamide of pharmaceutical relevance

Raman spectroscopy, X-ray powder diffraction/X-ray crystallography and differential scanning calorimetry have been used to study the phenomenon of co-crystal formation in stoichiometric mixtures of salicylic acid with benzamide. Raman spectroscopy was particularly useful for the characterization of the products and was used to determine the nature of the interactions in the co-crystals. It was observed that little change in the vibrational modes associated with the phenyl groups of the respective reactants took place upon co-crystal formation, but changes in intensities of the vibrational modes associated with the amide and the carboxylic acid groups were observed upon co-crystal formation. Several new vibrational bands were identified in the co-crystal which were not manifested in the physical mixture of both components and could be used as diagnostic features of co-crystal formation. © 2009 Springer-Verlag