Preparation and evaluation of a novel complex of cefixime by mechanochemical activation

To enhance the solubility and bioavailability of cefixime (CEF), novel non-covalent complexes were prepared through mechanochemical synthesis using either arabinogalactan (AG) or the disodium salt of glycyrrhizic acid (Na
2
GA). Solid-state interactions between CEF and Na
2
GA or AG were investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR). Liquid-state properties of the mechanochemically processed CEF/Na
2
GA complex were analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Parallel artificial membrane permeability assay (PAMPA) demonstrated increased permeability of CEF in the presence of Na
2
GA compared to pure CEF. Molecular dynamics simulations further elucidated the complexation behavior of CEF within these formulations. Additionally, both CEF/AG and CEF/Na
2
GA complexes showed significantly enhanced chemical stability over a 3-month storage period at 40°C and 75% relative humidity compared to unprocessed CEF. Pharmacokinetic studies in rats indicated that the oral bioavailability of CEF was nearly doubled when administered as complexes with either AG or Na
2
GA. Therefore, the economically viable mechanochemical synthesis of CEF complexes with AG or Na
2
GA represents a promising strategy for improving the solubility and bioavailability of CEF, potentially enabling more effective antibacterial formulations.