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Mechanochemical synthesis of novel metronidazole cocrystal: Structure characterization and pharmaceutical properties study.

Authors :
Chen J
Zhao ZY
Mu XF
Li XL
Tang J
Bi QQ
Source :
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 17; Vol. 738, pp. 150546. Date of Electronic Publication: 2024 Aug 14.
Publication Year :
2024

Abstract

A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bi Qingqing reports financial support was provided by Qingdao Key Health Discipline Development Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2104
Volume :
738
Database :
MEDLINE
Journal :
Biochemical and biophysical research communications
Publication Type :
Academic Journal
Accession number :
39154554
Full Text :
https://doi.org/10.1016/j.bbrc.2024.150546