Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-β-cyclodextrin

The interaction of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and a poorly water-soluble flavonoid, baicalein (Ba), chemically 5,6,7-trihydroxy flavone in solution and solid-state was studied. Ba/HP-β-CD solid systems were prepared by freeze-drying method. The formation of Ba/HP-β-CD complex in aqueous solution was demonstrated by UV spectroscopy, while Ba/HP-β-CD co-lyophilized product was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Through complexation with HP-β-CD, the solubility of Ba in neutral aqueous solution was improved significantly. The phase-solubility profile was AP-type, indicating the formation of higher-order complexes or complex aggregates. Ba/HP-β-CD solid powders were amorphous and show a significantly improved dissolution rate in comparison with free Ba. Comparison of the pharmacokinetics between Ba/HP-β-CD co-lyophilized product and free Ba was also performed in rats. The concentration of Ba and its mainly conjugated metabolite, 7-O-glucuronide of baicalein (BG) in rat plasma was determined by HPLC method. The in vivo results show that Ba/HP-β-CD co-lyophilized product exhibits the similar pharmacokinetics as that of free Ba after intravenous administration. Ba/HP-β-CD co-lyophilized product displays earlier tmax and higher Cmax of BG than free Ba after oral dosing. By comparing the AUC0–∞ of BG between oral dosing, the relative bioavailability of Ba/HP-β-CD co-lyophilized product to free Ba was 165.0%, which highlighted the evidence of significantly improved bioavailability of formulation of Ba with HP-β-CD.