Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-beta-cyclodextrin.
The interaction of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a poorly water-soluble flavonoid, baicalein (Ba), chemically 5,6,7-trihydroxy flavone in solution and solid-state was studied. Ba/HP-beta-CD solid systems were prepared by freeze-drying method. The formation of Ba/HP-beta-CD complex in aqueous solution was demonstrated by UV spectroscopy, while Ba/HP-beta-CD co-lyophilized product was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Through complexation with HP-beta-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-beta-CD solid powders were amorphous and show a significantly improved dissolution rate in comparison with free Ba. Comparison of the pharmacokinetics between Ba/HP-beta-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-beta-CD co-lyophilized product exhibits the similar pharmacokinetics as that of free Ba after intravenous administration. Ba/HP-beta-CD co-lyophilized product displays earlier tmax and higher Cmax of BG than free Ba after oral dosing. By comparing the AUC0-infinity of BG between oral dosing, the relative bioavailability of Ba/HP-beta-CD co-lyophilized product to free Ba was 165.0%, which highlighted the evidence of significantly improved bioavailability of formulation of Ba with HP-beta-CD.
Liu
Jun
J
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China.
Qiu
Liyan
L
Gao
Jianqing
J
Jin
Yi
Y
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D005612:Freeze Drying; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D044950:Flavanones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C006680:baicalein