American Chemical Society
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Spontaneous Solid-State Cocrystallization of Caffeine and Urea

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journal contribution
posted on 2020-01-15, 13:05 authored by Pól MacFhionnghaile, Clare M. Crowley, Patrick McArdle, Andrea Erxleben
The cocrystallization of caffeine and urea was monitored and analyzed using infrared spectroscopy, Raman microscopy, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction. The caffeine–urea cocrystal was shown to form spontaneously over several weeks under low energy mixing of the solids at room temperature and low relative humidity (<30%). Premilling the two coformers separately accelerated the process, and the cocrystal formation could be detected within 3 days. When caffeine and urea were milled together, the physical mixture that was confirmed by X-ray powder diffraction immediately after milling transformed to the cocrystal within hours of storage at room temperature and 30% relative humidity. The scanning electron microscopy images of the milled sample indicated the role of interparticle surface contact in the spontaneous solid-state reaction. Multivariate data analysis was used to find the optimum cooling crystallization conditions for obtaining cocrystals suitable for single crystal X-ray analysis.