元胡止痛方两种有效组分固体分散体的制备与评价

Preparation and Evaluation of the Solid Dispersions Loaded with Two Active Components of Yuanhu Zhitong Compound

为提高元胡止痛方中2个有效组分延胡索乙素(1)和欧前胡素(2)的口服生物利用度,采用溶剂挥发法制备其固体分散体。优化结果表明,载体材料宜选用聚乙烯吡咯烷酮(PVP K30),药物(1∶2=1∶1)与PVP K30的比例为1∶1。差示扫描量热和X-射线衍射分析结果表明,1和2均以无定形状态存在于制剂中。与原料药相比,1和2的溶解度和溶出度均显著增加。大鼠药动学试验结果显示,与单独灌胃给予1和2原料药相比,固体分散体组大鼠血浆中1和2的AUC得到显著提高(P<0.05)。以AUC_(0→t)计算,1和2的相对生物利用度分别为155%和187%。可见,固体分散体可同时提高这2种有效成分的溶解度、溶出度和口服吸收。

In order to improve the oral bioavailability of tetrahydropalmatine （1） and imperatorin （2）, two main active components of Yuanhu Zhitong compound, the solid dispersions were prepared by solvent evaporation method. The results of optimization showed that the product was prepared with polyvidone （PVP K30） as the carriers, and the ratio of two-component mixture （1 ： 2=1 ： 1） to carrier was 1 ： 1. The results of differential scanning calorimetry （DSC） and X-ray diffraction （XRD） showed that 1 and 2 were present in amorphous forms in the solid dispersions. The solubilities and dissolutions of 1 and 2 were significantly enhanced compared with their bulk drug. The result of pharmacokinetic study in rats showed that the AUC values of 1 and 2 in solid dispersion group were significant higher than those in 1 or 2 administration alone group （P〈0.05）. The relative bioavailability of 1 and 2 were 155% and 187% calculated by AUC0-t. It indicated that the solid dispersion could simultaneously improve the solubility, dissolution and oral absorption of 1 and 2.