橙皮苷磷脂复合物固体分散体的制备、表征及其体内药动学研究

Preparation,characterization and in vivo pharmacokinetics of solid dispersions of hesperidin phospholipids complex

目的制备、表征橙皮苷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,X射线粉末衍射(XRPD)分析晶型,测定表观溶解度、体外溶出度。大鼠灌胃给药(80 mg/kg)后于0.167、0.5、0.75、1、2、3、4、6、8、10、12 h采血,HPLC法测定橙皮苷血药浓度,计算主要药动学参数。结果橙皮苷以无定型状态存在,表明固体分散体制备成功。固体分散体在水、正辛醇中的表观溶解度较原料药分别提高至8.76、4.29倍,累积溶出度明显增加。固体分散体t1/2、Cmax、AUC0~t、AUC0~∞高于原料药(P<0.05,P<0.01),Tmax无明显变化(P>0.05),相对生物利用度提高至2.54倍。结论磷脂复合物固体分散体可改善橙皮苷溶解性,提高其口服生物利用度。

AIM To prepare and characterize the solid dispersions of hesperidin phospholipids complex and to investigate their in vivo pharmacokinetics.METHODS For the solid dispersions prepared by solvent evaporation method,their crystal form was analyzed by X-ray powder diffraction(XRPD),and the apparent solubility and in vitro dissolution rate were determined.Rats were given intragastric administration(80 mg/kg),after which blood collection was performed at 0.167,0.5,0.75,1,2,3,4,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of hesperidin,and main pharmacokinetic parameters were calculated.RESULTS Hesperidin existed in an amorphous state,demonstrating that the solid dispersions were successfully prepared.The apparent solubilities of solid dispersions in water and n-octanol was enhanced to 8.76 times and 4.29 times as compared with those of raw medicine,repectively,along with obviously increased accumulative dissolution rate.The solid dispersions displayed higher t1/2,Cmax,AUC0-t and AUC0-∞than raw medicine(P<0.05,P<0.01)without obvious change in Tmax(P>0.05),whose relative bioavailability was enhanced to 2.54 times.CONCLUSION Phospholipids complex solid dispersions can improve hesperidin solubility and enhance its oral bioavailability.