Inclusion Complex of Gedunin-2-Hydroxypropyl-Β-Cyclodextrin Prepared by Kneading and Freeze-Drying Methods: Synthesis and Structural Characterization

Abstract

Abstract The potential application of gedunin, a pharmacologically active limonoid, is limited in medicine because it has poor aqueous solubility. This study was aimed at preparation and characterization of an inclusion complex of gedunin and 2-hydroxypropyl-β-cyclodextrin (HBD) to increase the solubility in aqueous solvents and thus enhance the possibility of pharmaceutical formulation and oral administration of gedunin. Inclusion complex of gedunin isolated from Entandrophragma angolense heartwood with 2-hydroxypropyl-β-cyclodextrin (HBD) was prepared using freeze-drying and kneading methods. The gedunin-2-hydroxypropyl-β-cyclodextrin complex (GCD) was characterized using elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (1H-NMR) and X-ray diffraction analysis (XRD). Elemental analysis indicated that gedunin and HBD formed 1:1 stoichiometric inclusion complex. Results of FT-IR indicated that gedunin was stabilized in HBD cavity by intra-molecular hydrogen bonds and van der Waals forces. 1H-NMR revealed that the entire gedunin molecule was not trapped into the core of the HBD. Nevertheless, the fraction trapped may be sufficient to enhance the apparent solubility of gedunin. XRD results showed the formation of new solid crystalline phase. The results obtained by different characterization techniques clearly indicated that both kneading and freeze-drying methods led to inclusion complex formation which may enhance oral administration of gedunin.