Inclusion complex of ellagic acid with β-cyclodextrin: Characterization and in vitro anti-inflammatory evaluation

Freeze-dried inclusion complex of ellagic acid/beta-cyclodextrin (EACD) was investigated both in solution and solid state by means of aqueous solubility, in vitro dissolution, absorption, fluorescence, Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) and molecular modeling methods. The phase solubility study showed that ellagic acid formed 1:2 stoichiometric inclusion complex with beta-cyclodextrin (beta-CD). The FTIR study indicates that carbonyl group of ellagic acid interact with beta-CD. The NMR results demonstrate that ellagic acid was partly included into the beta-CD from the wider side of the cavity. Molecular modeling studies revealed that hydrogen bonding interactions played an important role in the inclusion process and higher negative values for the complexation energies imply that 1:2 complex was more stable than 1:1 complex. The solubility and in vitro dissolution of ellagic acid was significantly enhanced by complexation with beta-CD as compared to the free ellagic acid. Additionally, the complexation of EACD positively influences it's in vitro anti-inflammatory activity by protecting from protein denaturation and lysis of erythrocyte membrane. (C) 2015 Published by Elsevier B.V.