Identification and physicochemical characterization of caffeine-citric acid co-crystal polymorphs

The purpose of the present study was to identify a new caffeine-citric acid co-crystal (CA-CI) polymorph and characterize three CA-CI polymorphs. The stability order among the three CA-CI polymorphs was also determined. One new and two known CA-CI polymorphs were prepared by the liquid-assisted grinding method or the slurry methods. The three CA-CIs were then identified and characterized by powder X-ray diffraction (PXRD), thermal analysis, IR spectroscopy, Raman spectroscopy, and dynamic vapor sorption (DVS). The stability order of the CA-CIs was determined by the slurry conversion method. Each CA-CI showed distinct PXRD, IR, Raman, and DVS data. The melting points of CA-CIs were 131 °C (a new form, Form III), 141 °C (Form I), and 160 °C (Form II). The order of thermodynamic stability was CA-CI Form II > CA-CI Form I > CA-CI Form III. CA-CI Forms I and II were relatively stable against humidity compared to CA, CI and CA-CI Form III.

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