木犀草素-聚乙二醇400/PVP k30固体分散体的制备及体内外评价  

Preparation and evaluation in vitro and in vivo of luteolin-PEG 400/PVP k30 solid dispersion

作　　者：吕鑫科[1] 曾爱国 LÜXinke;ZENG Aiguo(Department of Pharmacy,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;School of Pharmacy,Health Science Center,Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]武汉大学中南医院药学部,武汉430071 [2]西安交通大学医学部药学院,西安710061

出　　处：《西北药学杂志》2023年第6期100-104,共5页Northwest Pharmaceutical Journal

基　　金：陕西省重点研发计划项目(编号:2021SF-113)。

摘　　要：目的制备木犀草素-聚乙二醇(PEG)400/PVP k30固体分散体,并评价其体外溶出和体内生物利用度。方法以PEG 400为溶剂、PVP k30为载体材料,用溶剂-熔融法制备木犀草素-PEG 400/PVP k30固体分散体,用差示扫描量热法(differential scanning calorimetry,DSC)和粉末X-线衍射法(powder X-ray diffraction,PXRD)分析木犀草素在固体分散体中的分散状态,并考察固体分散体对木犀草素溶解度和溶出度的影响。分别用木犀草素和木犀草素-PEG 400/PVP k30固体分散体灌胃SD大鼠,于预定时间采取血样,用HPLC法测定血浆样品中木犀草素的质量浓度,计算药动学参数。结果DSC和PXRD结果显示,木犀草素以无定形状态或分子状态分散在固体分散体中。固体分散体将木犀草素的溶解度从0.60μg·mL^(-1)提高至25.06μg·mL^(-1),体外溶出度也显著提高。体内药动学参数显示,木犀草素-PEG 400/PVP k30固体分散体的达峰质量浓度提高了5倍,体内生物利用度提高了9倍。结论木犀草素-PEG 400/PVP k30固体分散体显著改善了木犀草素的溶出特性和吸收,提高了体内生物利用度。Objective To prepare luteolin-PEG 400/PVP k30 solid dispersion and evaluate its dissolution in vitro and bioavailability in vivo.Methods Luteolin-PEG 400/PVP k30 solid dispersion was prepared by solvent-melting method with PEG 400 as solvent and PVP k30 as carrier.The dispersion state of luteolin in solid dispersion was analyzed by differential scanning calorimetry(DSC)and powder X-ray diffraction(PXRD),and the effect of solid dispersion on the solubility and dissolution of luteolin was investigated.SD rats were administrated intragastrically with luteolin and luteolin-PEG 400/PVP k30 solid dispersion,respectively.The blood samples were collected at predetermined time points.The concentration of luteolin in plasma samples was determined by HPLC,and the pharmacokinetic parameters were calculated.Results DSC and PXRD results showed that luteolin was dispersed in solid dispersion in an amorphous or molecular state.The solid dispersion increased the solubility of luteolin from 0.60μg·mL^(-1)to 25.06μg·mL^(-1),and the dissolution in vitro was also greatly improved.The pharmacokinetic parameters in vivo showed that the peak concentration of luteolin in solid dispersion was increased by 5 times and the bioavailability in vivo was increased by 9 times.Conclusion Luteolin-PEG 400/PVP k30 solid dispersion significantly improved the dissolution characteristics and absorption of luteolin,and improved the bioavailability of luteolin in vivo.

关 键 词：木犀草素 固体分散体 聚乙二醇400 溶出度 生物利用度 

分 类 号：R94[医药卫生—药剂学]