来那替尼自微乳的制备、表征及生物利用度研究  

Preparation,characterization and bioavailability of neratinib self-microemulsion

作　　者：张雪 张强 程泽能 ZHANG Xue;ZHANG Qiang;CHENG Ze-neng(Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013;Hunan Huize Biopharma S&T Co.,Ltd.,Changsha 410000;School of Pharmacy,Xuzhou Medical University,Xuzhou Jiangsu 221000)

机构地区：[1]中南大学湘雅药学院,长沙410013 [2]湖南慧泽生物医药科技有限公司,长沙410000 [3]徐州医科大学药学院,江苏徐州221000

出　　处：《中南药学》2023年第1期92-99,共8页Central South Pharmacy

摘　　要：目的制备来那替尼自微乳并对其进行体内外质量评价。方法通过辅料溶解度和混合油相与表面活性剂相容性选择处方所用辅料;通过三元相图和星点设计-效应面法确定处方各辅料的比例;对来那替尼自微乳的粒径分布、Zeta电位、微观形态及稀释稳定性进行体外质量评价;通过比格犬体内药动学实验计算来那替尼自微乳的相对生物利用度。结果来那替尼自微乳处方:来那替尼35 mg,油酸200 mg,玉米油200 mg,RH40255 mg,Transcutol HP 345mg。来那替尼自微乳加水稀释后,平均粒径为(33.45±1.38)nm,Zeta电位为(-29.5±9.40)m V,透射电镜下为规则的球状且分布均匀,室温可保持6 h稳定。与原料药的混悬液相比,来那替尼自微乳在比格犬体内相对生物利用度为315%。结论来那替尼自微乳制剂可以显著提高生物利用度,有望成为来那替尼的新型给药制剂。Objective To prepare neratinib self-microemulsion and evaluate its quality.Methods The formulation of neratinib self-microemulsion was selected by the solubility,compatibility,ternary phase diagram,and central composite design-response surface methodology.The assessment of the prepared neratinib self-microemulsion in-vitro mainly covered particle size distribution,Zeta potential,micromorphology and dilution stability.Besides,the relative bioavailability of neratinib self-microemulsion was also evaluated by the pharmacokinetic test in Beagle dogs.Results The optimized formulation was composed of 35 mg neratinib,200 mg oleic acid,200 mg corn oil,255mg RH40,and 345 mg Transcutol HP.After water dilution,the mean particle size was(33.45±1.38)nm and the Zeta potential was(-29.5±9.40)mV.The transmission electron microscope indicated a regular spherical shape and uniform distribution.There was no significant change in particle size after 6 h at room temperature.Compared with the suspension,the relative bioavailability of selfmicroemulsion was 315%.Conclusion Neratinib self-microemulsion can significantly improve the bioavailability,which is likely to be a new drug delivery agent for neratinib.

关 键 词：来那替尼 自微乳给药系统 生物利用度 

分 类 号：R283[医药卫生—中药学] R285[医药卫生—中医学]