Structural insights and supramolecular description of Gliclazide and its Impurity F

Abstract

Gliclazide is an oral hypoglycemic antidiabetic drug classified by the Biopharmaceutics Classification System as a Class II with low aqueous solubility and high permeability, as mentioned in the WHO Model Lists of Essential Medicines. Gliclazide Impurity F, a specified impurity of Gliclazide, is listed in the European Pharmacopoeia. The present study analyzed molecular conformation, supramolecular arrangement by a Hirshfeld surface, and quantum theory calculations of atoms in molecules to understand the physicochemical properties caused by the structural difference of the two compounds. Also, theoretical calculations were carried out by DFT at a M062x/6–311++G** level of theory for Gliclazide and Gliclazide Impurity F in the gas phase. The geometric properties were compared to experimental data. The frontier molecular orbitals (HOMO/LUMO) and the MEP maps indicate the electron density, electronic transition energies, and hydrogen bond donor capacities of both molecular systems, which are helpful to describe Gliclazide stability in pharmaceutical formulations.