药学学报, 2019, 54(1): 48-53
引用本文:
殷一凡, 李卓越, 李慧, 郭阳, 张强, 张烜. 氟灭酸对索拉菲尼纳米骨架给药系统中索拉菲尼溶解度、溶出度和体内药动学行为的影响[J]. 药学学报, 2019, 54(1): 48-53.
YIN Yi-fan, LI Zhuo-yue, LI Hui, GUO Yang, ZHANG Qiang, ZHANG Xuan. Effect of flufenamic acid on solubility, dissolution and pharmacokinetic behavior of sorafenib in MSNM@SFN[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 48-53.

氟灭酸对索拉菲尼纳米骨架给药系统中索拉菲尼溶解度、溶出度和体内药动学行为的影响
殷一凡, 李卓越, 李慧, 郭阳, 张强, 张烜
北京大学药学院, 分子药剂学与新释药系统北京市重点实验室, 北京 100191
摘要:
考察氟灭酸(flufenamic acid,FFA)对索拉非尼纳米骨架给药系统[sorafenib loaded nanomatrix drug delivery system(MSNM@SFN)]中索拉菲尼(sorafenib,SFN)的溶解度、溶出度和体内药动学行为的影响。先制备MSNM@SFN,再与FFA物理混合,制备索拉菲尼纳米骨架给药系统联合氟灭酸(MSNM@SFN&FFA),考察MSNM@SFN&FFA中SFN的溶解度、溶出度和大鼠体内药动学行为,并与前期MSNM@SFN的相应数据进行比较,以确定FFA对MSNM@SFN中SFN的溶解度、溶出度和体内药动学行为的影响。动物实验动物实验均按照国际动物实验指导原则进行并被北京大学医学部实验动物中心伦理学委员会批准。结果表明,与MSNM@SFN相比,MSNM@SFN&FFA中SFN的溶解度、溶出度和大鼠体内药动学行为等无明显改变,说明MSNM@SFN与FFA混合后,FFA对SFN在MSNM@SFN中的溶解度、溶出度以及大鼠体内生物利用度等都无显著影响,为后续两药联用的制剂研究提供科学依据。
关键词:    索拉菲尼纳米骨架给药系统      氟灭酸      溶解度      溶出度      生物利用度     
Effect of flufenamic acid on solubility, dissolution and pharmacokinetic behavior of sorafenib in MSNM@SFN
YIN Yi-fan, LI Zhuo-yue, LI Hui, GUO Yang, ZHANG Qiang, ZHANG Xuan
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Abstract:
The aim of this study is to investigate the influence of flufenamic acid (FFA) on the solubility, dissolution and bioavailability of sorafenib (SFN) in the combined administration of the MSNM@SFN and FFA. The MSNM@SFN&FFA was prepared by mixing the MSNM@SFN with FFA. The solubility, dissolution and bioavailability of SFN in the MSNM@SFN&FFA complex was investigated in comparison with those of the MSNM@SFN. This study was performed following the National Institutes of Health guidelines for the use of experimental animals; all care and handling of animals were performed with the approval of the Experimental Animal Center of Peking University Health Science Center. The MSNM@SFN&FFA showed no significant influence on the solubility, dissolution and bioavailability of SFN when compared with the MSNM@SFN. These data indicated that FFA had almost no influence on the solubility, dissolution and bioavailability of SFN in the combined administration of MSNM@SFN and FFA, thus providing an experimental foundation for the subsequent formulation research on the combined usage of drugs.
Key words:    sorafenib loaded nanomatrix drug delivery system    flufenamic acid    solubility    dissolution    bioavailability   
收稿日期: 2018-05-31
DOI: 10.16438/j.0513-4870.2018-0512
基金项目: 国家重大科学研究计划项目(2015CB932102,2013CB932501);国家自然科学基金项目资助(81573360).
通讯作者: 张烜,Tel:86-10-82805765,E-mail:xuanzhang@bjmu.edu.cn
Email: xuanzhang@bjmu.edu.cn
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