Aqueous Solubility Enhancement of Some Flavones by Complexation with Cyclodextrins

The inclusion complexes of cyclodextrins (CDs) with flavones in aqueous solution were investigated by phase solubility measurements. The effect of β-cyclodextrin (β-CD), heptakis (2,6-di-O-methyl) β-cyclodextrin (DM-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility of three flavones, namely, chrysin, apigenin and luteolin was investigated, respectively. Solubility enhancements of all flavones obtained with three CDs followed the rank order: HP-β-CD > DM-β-CD > β-CD, and besides, CDs show higher stability constant on luteolin than that on others flavones. H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling was used to help establish the model of interaction of the CDs with luteolin. NMR spectroscopic analysis suggested that A-C ring, and part of the B ring of luteolin display favorable interaction with the CDs, which was also confirmed by docking studies based on the molecular simulation. The observed augmentation of solubility of luteolin by three CDs was explained by the difference of electrostatic interaction of each complex, especially hydrogen bonding.