Color tuning of an active pharmaceutical ingredient through cocrystallization: a case study of a metronidazole–pyrogallol cocrystal

Abstract

The last two decades have witnessed a rising interest in modulating the physicochemical properties of active pharmaceutical ingredients (APIs) through cocrystallization. The present study reports a new cocrystal of antimicrobial drug metronidazole (MNZ) using pyrogallol (PYR) as a cocrystal former, namely the MNZ–PYR cocrystal. The crystal structure of the MNZ–PYR cocrystal is studied by means of single-crystal X-ray diffraction, infrared spectroscopy, thermal analysis, and density functional theory calculations. The MNZ–PYR cocrystal shows an increased dissolution rate compared to MNZ due to the high energy conformer of PYR in the crystal lattice of the cocrystal. The formation of the MNZ–PYR cocrystal leads to a color shift from white (raw MNZ and PYR) to yellow, which is characterized by UV-vis spectroscopy and interpreted theoretically by means of time-dependent density functional theory calculations. The results suggest that the cocrystal strategy may be used for color tuning of APIs, offering opportunities for formulation development.