Preparation, characterization, and evaluation of the complexes of carbamazepine with polysaccharide arabinogalactan and saponin disodium glycyrrhizate produced by mechanochemical activation

In the present study, novel non-covalent associate complexes of carbamazepine (CBZ) with the natural polysaccharide arabinogalactan (AG) and the disodium salt of glycyrrhizic acid (Na2GA) were prepared using a mechanochemical method to enhance the solubility and oral bioavailability of CBZ. The solid-state interactions between CBZ and AG or Na2GA were characterized by FT-IR, DSC, powder XRD, and SEM. The properties of mechanochemically processed CBZ/Na2GA in solution were further examined using DLS and TEM. A parallel artificial membrane permeability assay (PAMPA) demonstrated a marked increase in CBZ permeability in the presence of Na2GA compared with pure CBZ. Moreover, accelerated stability testing (+40 °C for 3 months) revealed a significant improvement in the chemical stability of CBZ/AG and CBZ/Na2GA complexes compared with the unmodified drug. Pharmacokinetic studies in rats further showed that oral administration of the complexes resulted in approximately a fivefold increase in CBZ bioavailability. Collectively, these findings indicate that the simple, low-cost mechanochemical method enables the synthesis of stable CBZ-AG and CBZ-Na2GA complexes, and that such non-covalent associates represent a promising strategy to improve CBZ solubility and oral bioavailability, offering potential for more effective antiepileptic therapy.