白杨素磷脂复合物固体分散体的制备及其体内药动学研究

Preparation and in vivo pharmacokinetics of solid dispersions of chrysin phospholipids complex

目的制备白杨素磷脂复合物固体分散体,并考察其体内药动学。方法溶剂挥发法制备固体分散体,测定体外溶出、表观溶解度,采用XRPD进行晶型分析。大鼠灌胃给药(20 mg/kg)后,于0.167、0.5、1、1.5、2、2.5、3、4、8、12 h采血,HPLC法测定白杨素血药浓度,计算主要药动学参数。结果药载比(磷脂复合物-PVP K30)为1∶6时,固体分散体240 min内累积溶出度达94.6%。白杨素在固体分散体中以无定型状态存在。与原料药、磷脂复合物比较,固体分散体在水、正辛醇中的表观溶解度升高(P<0.01),tmax缩短(P<0.05),Cmax、AUC0~t、AUC0~∞升高(P<0.01),相对生物利用度增加至2.16倍。结论固体分散体可改善白杨素磷脂复合物的体外溶出度和体内生物利用度。

AIM To prepare the solid dispersions of chrysin phospholipids complex and to investigate their in vivo pharmacokinetics.METHODS Solvent evaporation method was adopted in the preparation of solid dispersions, after which the in vitro dissolution and apparent solubility were determined, and XRPD was applied to analyzing crystalline form. Rats were given intragastric administration(20 mg/kg), then blood collection was made at 0.167, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 h, HPLC was adopted in the plasma concentration determination of chrysin, and main pharmacokinetic parameters were calculated.RESULTS At the drug-carrier ratio(phospholipids complex-PVP K30) of 1∶6, the accumulative dissolution rate of solid dispersions reached 94.6%. Chrysin existed in an amorphous state in the solid dispersions. Compared with the raw medicine and phospholipids complex, the solid dispersions demonstrated increased apparent solubilities in water and n-octanol(P<0.01), along with shortened tmax (P<0.05) and elevated Cmax, AUC0-t, AUC0-∞(P<0.01), the relative bioavailability was enhanced to 2.16 times.CONCLUSION Solid dispersions can improve the in vitro dissolution rate and in vivo bioavailability of chrysin phospholipids complex.