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On the issues of resolving a low melting combination as a definite eutectic or an elusive cocrystal: A critical evaluation

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Abstract

Cocrystals and eutectics are different yet related crystalline multi-component adducts with diverse applications in pharmaceutical and materials fields. Recently, they were shown to be alternate products of cocrystallization experiments. Whereas a cocrystal shows distinct diffraction, spectroscopic and thermal signatures as compared to parent components, the hallmark of a eutectic is its low melting nature. However, in certain cases, there can be a problem when one resorts to design a cocrystal and assess its formation vis-à-vis a eutectic. In the absence of a gold standard method to make a cocrystal, it is often difficult to judge how exhaustive should the cocrystallization trials be to ensure the accomplishment of a desired/putative cocrystal. Further, a cocrystal can manifest with intermolecular interactions and/or crystal structure similar to that of its parent compounds such that the conventional diffraction and spectroscopic techniques will be of little help to conclusively infer the formation of cocrystal in the lack of single crystals. Such situations combined with low melting behavior of a combination brings the complication of resolving the combination as a cocrystal or eutectic since now both the adducts share common features. Based on the curious case of Caffeine–Benzoic acid combination, this study aims to unfold the intricate issues related to the design, formation and characterization of cocrystals and eutectics for a way forward. The utility of heteronuclear seeding methodology in establishing a given combination as a cocrystal-forming one or a eutectic-forming one in four known systems is appraised.

The notion of mutual exclusivity of cocrystal and eutectic from cocrystallization and issues related to their structural organization and manifestation are discussed. The potential of hetero seeding in facilitating the formation of a putative cocrystal and thus establishing a given combination as a cocrystal-forming one or a eutectic-forming one is appraised.

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Acknowledgements

I thank the University Grants Commission, India, for Dr. D. S. Kothari Postdoctoral Fellowship. I profusely thank Prof. T. N. Guru Row, Indian Institute of Science, for his encouragement to write this monograph. My special thanks to Mr. Ramesh Ganduri, Indian Institute of Science, for his help in collecting the PXRD patterns. Infrastructural facilities of the Institute are gratefully acknowledged.

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  1. Solid State and Structural Chemistry Unit, Indian Institute of Science, Bengaluru, 560 012, India

    SURYANARAYAN CHERUKUVADA

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Supplementary Information (SI)

Supramolecular schematics, packing diagrams of cocrystals, preparation and characterization of cocrystals and eutectics, figures S1–S5 and table S1 are available in Supplementary Information at www.ias.ac.in/chemsci.

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CHERUKUVADA, S. On the issues of resolving a low melting combination as a definite eutectic or an elusive cocrystal: A critical evaluation. J Chem Sci 128, 487–499 (2016). https://doi.org/10.1007/s12039-016-1055-7

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