目的 制备槲皮素固体分散体（quercetin solid dispersions，QSD），提高槲皮素的溶出度及其大鼠口服生物利用度。方法 以聚维酮K₃₀（PVPK₃₀）、聚乙二醇6000（PEG6000）和木糖醇为载体，用溶剂法、熔融-溶剂法制备QSD；通过体外溶出度测定、差示扫描量热法（DSC）和X射线粉末衍射法（XRPD）评价所制备的QSD；采用液质联用技术（HPLC-MS）测定大鼠体内血药浓度。结果 制备的QSD均可以显著提高槲皮素的溶出度，其中槲皮素-PVPK₃₀-木糖醇（1：5：1）制备的QSD效果最好，5 min和60 min时的溶出率分别为40.63%和68.58%，而槲皮素原料药在相同时间的溶出率只有0.26%和1.66%。DSC和XRPD证明药物槲皮素以无定形状态存在于QSD中。大鼠ig给药后，QSD的生物利用度约为原药料的61倍。结论 制备的QSD可以显著提高药物溶出度和大鼠体内生物利用度。

Objective Quercetin solid dispersions (QSD) with hydrophilic carriers were prepared in order to enhance its dissolution rate and oral bioavailability in rats. Methods QSD with different ratios of polyvinylpyrrolidone (PVPK₃₀), PEG6000, and xylitol were prepared by solvent method or melting-solvent method. Dissolution characteristics of QSD were evaluated and compared with that of the pure drug. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to examine the crystallinity of solid dispersion, physical mixture, carriers and quercetin. Drug plasma concentrations were determined by high performance liquid chromatography mass spectrum (HPLC-MS) after oral administration in rats. Results The dissolution rate of quercetin from its solid dispersions was greatly enhanced. Dissolution percentages from the solid dispersion of quercentin-PVPK₃₀-xylitol in 1:5:1 weight ratio were 40.63% and 68.58% at 5 min and 60 min respectively, while in the same time only 0.26% and 1.66% from pure quercetin. The results of DSC and XRPD demonstrated that quercetin was amorphously dispersed in solid dispersion. Oral bioavailability in rats of QSD was about 61-fold higher than that of pure drug. Conclusion QSD significantly improved quercetin dissolution rate and bioavailability in rat.

国家科技重大专项（2014ZX09507001）