欧前胡素固体分散体的制备及其体内药动学研究

目的制备欧前胡素固体分散体,并考察其体内药动学。方法溶剂挥发法制备固体分散体后,检测欧前胡素存在状态,并测定溶解度、溶出率、累积溶出度。大鼠随机分为2组,分别灌胃给予欧前胡素及其固体分散体0??3%CMC?Na混悬液(25 mg/kg),于0.25、0.5、1、1.5、2、3、4、6、8、12 h采血,HPLC法测定欧前胡素血药浓度,计算主要药动学参数。结果欧前胡素以结晶型状态存在,制成固体分散体后转变为无定型状态,溶解度、溶出率、累积溶出度明显升高。与原料药比较,固体分散体t_max缩短(P<0.05),C_max、AUC_0-t、AUC_0-∞升高(P<0.01),相对生物利用度增加至2??03倍。结论固体分散体可改善欧前胡素溶解度、溶出率、累积溶出度,促进其体内吸收。

Preparation and in vivo pharmacokinetics of imperatorin solid dispersions

AIM To prepare imperatorin solid dispersions and to investigate their in vivo pharmacokinetics.METHODS Solid dispersions were prepared by solvent evaporation method,after which the existence state of imperatorin was detected,and the solubility,dissolution rate and accumulative dissolution rate were determined.Rats were randomly assigned into two groups and given intragastric administeration of the 0.3%CMC?Na suspensions of imperatorin and its solid dispersions(25 mg/kg),respectively,after which blood collection was performed at 0.25,0.5,1,1.5,2,3,4,6,8,12 h.HPLC was adopted in the plasma concentration determination of imperatorin,and the main pharmacokinetic parameters were calculated.RESULTS Imperatorin existed in a crystalline state and changed into an amorphous state after being prepared into solid dispersions,whose solubility,dissolution rate and accumulative dissolution rate were obviously increased.Compared with raw medicine,the solid dispersions demonstrated shortened tmax(P<0.05),and increased Cmax,AUC_0-t and AUC_0-∞(P<0.01),whose relative bioavailability was enhanced to 2.03 times.CONCLUSION Solid dispersions can improve the solubility,dissolution rate and accumulative dissolution rate of imperatorin and promote its in vivo absorption.