In recent decades, the design of cocrystals has developed significantly due to the unique characteristics and advantages of cocrystals, which help to improve the physicochem. properties of drugs, esp. soly. Zwitterions are attractive and interesting co-formers. However, the physicochem. properties of cocrystals with zwitterionic co-formers, i.e. zwitterionic cocrystals, have not been adequately evaluated. In this study, solid-state characterization of a newly developed zwitterionic cocrystal of diclofenac (DFA), a non-steroidal anti-inflammatory drug, and the amino acid L-proline (PRO) was performed using Fourier-transform IR spectroscopy, differential scanning calorimetry, and powder X-ray diffraction (PXRD) analyses. In addn., the crystal structure of the cocrystal (DFA-PRO) was detd. by single-crystal X-ray diffraction anal., after which the zwitterionic structure was confirmed. The cocrystn. during co-grinding, which was investigated by PXRD, followed first-order kinetics. Furthermore, the soly. of the zwitterionic cocrystals was 7.5-times higher than that of the DFA crystals. The results indicate that the cocrystal is stable under ambient conditions; however, it hydrates and transforms into a mixt. of L-proline monohydrate crystals and DFA crystals under conditions of high humidity. [on SciFinder(R)]