Liu Jun, Qiu Liyan, Gao Jianqing, Jin Yi
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China.
Int J Pharm. 2006 Apr 7;312(1-2):137-43. doi: 10.1016/j.ijpharm.2006.01.011. Epub 2006 Feb 3.
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.
研究了2-羟丙基-β-环糊精（HP-β-CD）与一种水溶性差的黄酮类化合物黄芩苷（Ba）（化学名为5,6,7-三羟基黄酮）在溶液和固态下的相互作用。通过冷冻干燥法制备了Ba/HP-β-CD固体体系。紫外光谱法证明了水溶液中Ba/HP-β-CD复合物的形成，而差示扫描量热法（DSC）和X射线衍射法（XRD）对Ba/HP-β-CD共冻干产物进行了表征。通过与HP-β-CD络合，Ba在中性水溶液中的溶解度显著提高。相溶解度曲线为AP型，表明形成了高阶复合物或复合聚集体。Ba/HP-β-CD固体粉末为无定形，与游离Ba相比，其溶解速率显著提高。还在大鼠中比较了Ba/HP-β-CD共冻干产物和游离Ba的药代动力学。采用高效液相色谱法测定大鼠血浆中Ba及其主要结合代谢物黄芩苷7-O-葡萄糖醛酸苷（BG）的浓度。体内结果表明，静脉给药后，Ba/HP-β-CD共冻干产物的药代动力学与游离Ba相似。口服给药后，Ba/HP-β-CD共冻干产物的BG的tmax出现得更早，Cmax更高。通过比较口服给药后BG的AUC0-∞，Ba/HP-β-CD共冻干产物相对于游离Ba的相对生物利用度为165.0%，这突出了HP-β-CD与Ba制剂生物利用度显著提高的证据。
