Comprehensive evaluation of solubilization of flavonoids by various cyclodextrins using high performance liquid chromatography and chemometry

Abstract

Flavonoids have many pharmacological activities, but the water solubility is poor, Cyclodextrin (CD) can be used to increase the solubility of flavonoids through making flavonoids into their cavities. While various CDs have different solubilization effects on flavonoids. Therefore, the purpose of this study was to evaluate the solubilization of flavonoids by three classes of cyclodextrins by Chemometrics (I native CDs: alpha-cyclodextrin (α-CD), beta-cyclodextrin (β-CD) and gamma-cyclodextrin (γ-CD); II hydrophilic CD derivatives: methyl-β-cyclodextrin (Me-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); III ionic CD derivative: sulfobutyl ether β-cyclodextrin (SBE-β-CD)). All selected CDs had significant solubilization effects (P < 0.01). The solubilization coefficients of six kinds of CDs on flavonoids were α-CD: 41.77, γ-CD: 61.81, β-CD: 143.45, HP-β-CD: 415.43, Me-β-CD: 558.53, SBE-β-CD: 709.56, respectively. Phase solubility study indicated that six kinds of CDs and kaempferide can form inclusion complexes with 1:1 M ratio, association constants (Ka) of inclusion compounds were kaempferide-α-CD: 808 L/mol, kaempferide-β-CD: 1541 L/mol, kaempferide-γ-CD: 1191 L/mol, kaempferide-HP-β-CD: 9335 L/mol, kaempferide-Me-β-CD: 10,421 L/mol, kaempferide-SBE-β-CD: 12,502 L/mol, respectively. The study showed that SBE-β-CD has the best solubilization effect on flavonoids, therefore, SBE-β-CD may be widely used as a solubilizing agent for flavonoids.