Preparation, characterization, in vitro and in vivo evaluation of metronidazole–gallic acid cocrystal: A combined experimental and theoretical investigation

Abstract

Pharmaceutical cocrystal as an alternative modification strategy presents opportunities for the formulation development of drugs with undesirable pharmacokinetic properties. Metronidazole (MNZ) is a water-soluble antimicrobial drug that can cause high plasma concentration peaks after administration, which may relate to serious encephalopathy. In the present study, the properties of MNZ were optimized through a cocrystallization strategy. A cocrystal of MNZ is prepared using gallic acid (GA) as cocrystal former. The structure of the prepared MNZ–GA cocrystal is studied by means of molecular dynamics and density functional theory calculations, powder X-ray diffraction, infrared spectroscopy, and thermal analysis. Comparative studies on the dissolution and absorption behaviors of raw MNZ and MNZ–GA cocrystal are completed. The results show that the MNZ–GA cocrystal exhibits lower Cmax and longer Tmax than pure metronidazole, suggesting that the prepared MNZ–GA cocrystal may find application in the formulation of MNZ.