二氢杨梅素固体分散体的制备及其体内药动学研究

目的制备二氢杨梅素固体分散体,并研究其体内药动学。方法以PVP K30为载体,溶剂挥发法制备固体分散体,考察其溶解度和体外溶出。18只大鼠随机分为3组,分别灌胃给予原料药、物理混合物、固体分散体0.5%CMC-Na混悬液(150 mg/kg),于0.167、0.25、0.5、0.75、1、2、4、6、8、12 h取血,HPLC法测定血药浓度,计算主要药动学参数。结果二氢杨梅素制成固体分散体后以无定型状态存在,其表观溶解度提高了9.8倍,累积溶出度增加。与原料药、物理混合物比较,固体分散体t_max缩短(P<0.05),C_max、AUC_0～t、AUC_0～∞升高(P<0.05,P<0.01),生物利用度提高了2.66倍。结论固体分散体技术可明显促进二氢杨梅素体内吸收,提高其生物利用度。

Preparation and in vivo pharmacokinetics of dihydromyricetin solid dispersions

AIM To prepare dihydromyricetin solid dispersions and to study their in vivo pharmacokinetics.METHODS Solvent evaporation method was adopted in the preparation of solid dispersions with PVP K30 as a carrier, after which the solubility and in vitro dissolution were investigated. Eighteen rats were randomly assigned into three groups and given intragastric administration of raw medicine, physical mixture and 0.5% CMC-Na suspensions of solid dispersions(150 mg/kg), respectively, blood collection was made at 0.167, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 h, HPLC was applied to determining plasma concentration, and main pharmacokinetic parameters were calculated.RESULTS Dihydromyricetin existed in an amorphous state after being prepared into solid dispersions, whose apparent solubility was enhanced by 9.8 times with increased accumulative dissolution rate. Compared with raw medicine and physical mixture, the solid dispersions demonstrated shortened tmax(P<0.05) and elevated Cmax, AUC0-t, AUC0-∞(P<0.05, P<0.01), and the bioavailability was enhanced by 2.66 times.CONCLUSION Solid dispersion technology can obviously promote the in vivo absorption of dihydromyricetin and enhance its bioavailability.