甘草素固体分散体的制备及体内药动学研究

Preparation and in vivo pharmacokinetics of liquiritigenin solid dispersion

目的 制备甘草素固体分散体,提高其口服生物利用度。方法 使用聚乙烯吡咯烷酮K30(PVP K30)和介孔二氧化硅,采用溶剂挥发法制备甘草素固体分散体。通过测定PVP K30对甘草素的增溶效果,筛选出甘草素与PVP K30的最佳比例;使用介孔二氧化硅作为吸收剂,除去有机溶剂后,得到固体分散体。以差示扫描量热法、X射线衍射分析和红外光谱对固体分散体进行表征;对比了甘草素原料药与固体分散体的体外溶出,并通过体内药代动力学评价固体分散体的生物利用度。结果 当甘草素与PVP K30比例为1∶8时,PVP K30对甘草素的增溶效果最好;加入介孔二氧化硅作为吸收剂,制备出的固体分散体,经过表征,甘草素能够以无定型状态分布其中;体外溶出时,在60 min内的累积溶出率可达到95%,有效提高了甘草素的溶出度,并且进行大鼠体内药代动力学的结果验证,固体分散体的相对生物利用度增加至7.08倍。结论 将甘草素制备成固体分散体,能够显著提高其溶出度和口服生物利用度。

Objective To prepare liquiritigenin solid dispersion and improve its oral bioavailability.Methods Liquiritigenin solid dispersion was prepared by solvent evaporation method with polyvinylpyrrolidone K30 (PVP K30) and mesoporous silica.According to the solubilizing effect of PVP K30 on liquiritigenin,the optimal ratio of liquiritigenin and PVP K30 was screened out.Mesoporous silica was used as the absorbent.After the removal of organic solvents,solid dispersion was obtained.Differential scanning calorimetry,X-ray diffraction analysis and infrared spectroscopy were used to characterize the solid dispersion.The in vitro dissolution rate of the solid dispersion and pure liquiritigenin was compared,and the bioavailability of the solid dispersion was evaluated by in vivo pharmacokinetics.Results When the optimal ratio of liquiritigenin and PVP K30 was 1∶8,PVP K30 had the best solubilizing effect on liquiritigenin.The characterization indicated that liquiritigenin formed solid dispersion with PVP K30 and was distributed in the mesoporous silica in an amorphous state.The cumulative dissolution rate reached over 95% within 60 min,greatly improving the solubility.The in vivo pharmacokinetics in rats verified that the relative bioavailability of the solid dispersion increased to 7.08 times.Conclusion Liquiritigenin solid dispersion can greatly improve its solubility and oral bioavailability.