阿瑞吡坦磷脂复合物静注亚微乳的制备及质量评价  

Preparation and quality evaluation of aprepitant phospholipid complex injectable microemulsion

作　　者：武晨思 耿丹丹 王春艳[2] 张艺蓉 王贺平 赵利刚 WU Chensi;GENG Dandan;WANG Chunyan;ZHANG Yirong;WANG Heping;ZHAO Ligang(School of Phamacy,North China University of Science and Technology,Tangshan 063210,China;Pharmacy Department,Tangshan Maternal&Child Health Care Hospital,Tangshan 063000,China;Tangshan Key Lab.of Novel Preparations and Drug Release Technology,Tangshan 063210,China)

机构地区：[1]华北理工大学药学院,河北唐山063210 [2]唐山市妇幼保健院药剂科,河北唐山063000 [3]唐山市新型药物制剂与释药技术重点实验室,河北唐山063210

出　　处：《沈阳药科大学学报》2022年第10期1165-1173,共9页Journal of Shenyang Pharmaceutical University

基　　金：河北省“第三批青年拔尖人才”项目;华北理工大学杰出青年基金项目(JQ201713)。

摘　　要：目的 制备静脉注射阿瑞吡坦亚微乳,对其理化性质和稳定性进行评价。方法 通过高压均质法制备阿瑞吡坦磷脂复合物亚微乳,并用X-射线衍射法和红外光谱法分析磷脂复合物;采用单因素试验法优化制备工艺参数,对乳剂的粒径、多分散指数、Zeta电位、pH值、渗透压、包封率、含量和稳定性进行考察;测定其溶血率,并进行体外释药模型拟合。结果 X-射线衍射法和红外光谱法均证实阿瑞吡坦可与磷脂形成复合物,最佳工艺下制得乳剂外观为淡黄色的均匀乳状液体,平均粒径为(82.82±1.56)nm,多分散指数为0.200±0.001,Zeta电位为(-52.20±2.43)mV,pH值为8.20±0.03,渗透压(298.0±2.2)mOsmol·kg^(-1),载药量(7.11±0.05)g·L^(-1),包封率(98.76±1.37)%,溶血率低于安全阈值,体外释药符合Higuchi模型,在4℃条件下放置12个月稳定。结论 所制备的静注阿瑞吡坦亚微乳粒径分布均匀,载药量高,理化性质稳定,安全性高,可进一步用于临床前研究。Objective To develop a microemulsion of aprepitant for intravenous injection and to investigate its physicochemical characters and stability.Methods The aprepitant injectable microemulsion loaded with the aprepitant phospholipid complex was prepared by high pressure homogenization method, and the phospholipid complex was analyzed by X-ray diffraction method(XRD) and Fourier transform infrared spectrum(FT-IR).Single factor experiment was employed to optimize preparation process, and then the particle size, polydispersity index, Zeta potential, pH value, osmotic pressure, entrapment efficiency, drug loading efficiency and stability were investigated respectively.Finally, the hemolytic activities and in vitro release were also evaluated.Results XRD and FT-IR verified the formation of aprepitant complex with phospholipid.The microemulsion was amber liquid.The physicochemical characterization of the optimal emulsion was listed as follow: mean particle size was(82.82±1.56) nm, polydispersity index was(0.200±0.001),Zeta potential was(-52.20±2.43) mV,pH value was(8.20±0.03),osmotic pressure was(298.0±2.2) mOsmol·kg^(-1),drug loading was(7.11±0.05) g·L^(-1),entrapment efficiency was(98.76±1.37) %.The hemolysis rate of emulsion was significant below the safety threshold, and in vitro release behavior was matched to Higuchi model equation.Additionally, the emulsion was stable at 4 ℃ for 12 months.Conclusion The aprepitant injectable microemulsion exhibits high safety, excellent stability, uniform size distribution and high drug loading, which can be used for preclinical research in future.

关 键 词：阿瑞吡坦 亚微乳 磷脂复合物 高压均质 理化性质 稳定性 

分 类 号：R94[医药卫生—药剂学]