ENHANCEMENT OF WATER SOLUBILITY OF HESPERETIN AND NARINGENIN BY COMPLEXATION WITH β-CYCLODEXTRIN AND ITS DIMETHYL DERIVATIVE

Abstract

Hesperetin and naringenin, the flavonoids of the class flavanones, are abundant in citrus fruits. They are widely applied in food products to enhance the health function as well as used in developing nutraceutical and pharmaceutical products. A limiting factor hampering the use of flavonoids in many applications is its low water solubility and stability. In the present study, the inclusion complex with β-cyclodextrin and dimethyl derivative to solve this problem is our aim. Molecular behaviours of inclusion complex between hesperetin or naringenin and β-CD/DM-β-CD, were theoretically investigated using the molecular dynamics simulation and free energy calculation. Both hesperetin and naringenin most likely preferred to bind with CDs cavity via the phenyl ring with a formation of strong hydrogen bonds. The system stability and solubility of the two flavanones in complex with DM-β-CD was considerably more stable and soluble than that with β-CD. To support these results, we examined the phase solubility diagram of the two flavanones inclusion complexes. The result showed the formation of soluble complex as AL type, indicating increase in flavanone stability when cyclodextrin was increased, with higher solubility of the DM-β-CD complexes. Solid complexes were prepared and DSC and FTIR were used to confirm the inclusion complex. From the DSC profile, the endothermic peak of free hesperetin and naringenin in the 1:1 inclusion complex formed by freeze-drying method disappeared, with the appearance of a new endothermic peak. This implied that the real inclusion complex was formed while the kneading method did not result in the formation of inclusion complex. Moreover, we examined the release of flavanones from the inclusion complexes compared to the free flavanones by dissolution method. It is clearly seen that the complexation with DM-β-CD made better release of both flavanones to the aqueous solution than with β-CD complexes.