摘要
目的 研究人干扰素α2b(human interferon α2b,hIFN α2b)溶液经加速和长期稳定性试验条件下放置后,其雾化吸入性能及生物活性的变化。评估hIFN α2b溶液在效期内以雾化吸入方式给药治疗儿童呼吸道合胞病毒引起的下呼吸道感染的适宜性。方法 应用激光衍射仪测定雾化液滴实时粒度大小及分布;采用新一代药用撞击器测定hIFN α2b雾化后的空气动力学性质;应用呼吸模拟器测定递送速率和递送总量;采用细胞病变抑制法测定雾化气溶胶中hIFN α2b的生物学活性。结果 hIFN α2b溶液雾化后液滴的Dx(50)为3.57μm;空气动力学质量中值粒径为3.31μm,微细粒子分数为76.9%,几何标准偏差为1.94;儿童呼吸模式下,递送速率和递送总量分别为0.68×10^(5)IU·min^(-1)和5.31×10^(5) IU。加速稳定性试验条件下储存6个月及长期稳定性试验条件下储存24个月后,样品雾化液滴大小及分布、空气动力学参数、递送性能及雾化后生物活性与初始相比,RSD均<6%。结论 hIFN α2b溶液雾化液滴大小及空气动力学性质适宜将药物递送至下呼吸道;在加速稳定性试验条件下储存6个月和长期稳定性试验条件下储存24个月后,吸入性能及雾化后的生物学活性指标无明显变化。
OBJECTIVE To investigate the change of the human interferonα2b(hIFNα2b)solution in inhalability and bioactivity following storage under accelerated and long-term stability testing conditions.And to evaluate the suitability for pulmonary delivery of hIFNα2b through nebulization,specifically for treating lower respiratory tract infections caused by respiratory syncytial virus in children within the product’s shelf life.METHODS The real-time droplet size and distribution of the nebulized hIFNα2b were evaluated using a laser diffraction,while the aerodynamic particle size distribution(APSD)was analyzed with the next generation pharmaceutical impactor(NGI).The respirable drug delivery rate and total delivered dose were determined under a breathing simulator(BRS).Additionally,the bioactivity of hIFNα2b in aerosol was measured with a cytopathic-effect inhibition assay.RESULTS The droplet size distribution analysis revealed a Dx(50)of 3.57μm when utilizing a jet nebulizer.Aerodynamically,the aerosol exhibited a fine particle fraction(FPF)of 76.9%and a mass median aerodynamic diameter(MMAD)of 3.31μm,with a geometric standard deviation(GSD)of 1.94.The delivery rate and total delivered dose under a child breathing pattern were 0.68×10^(5) IU·min^(−1) and 5.31×10^(5) IU,respectively.Results showed that no significant change was observed in the droplet size distribution,aerodynamic parameters,delivery efficiency and the bioactivity of aerosol after storage under accelerated stability testing conditions for 6 months and long-term stability testing conditions for 24 months.All relative standard deviation(RSD)values were<6%.CONCLUSION The droplet size of hIFNα2b aerosol is suitable for delivering to the lower respiratory tract after nebulization with a jet nebulizer.Furthermore,no significant change is found in the inhalability or bioactivity of the nebulized hIFNα2b under accelerated stability testing conditions for 6 months and long-term stability testing conditions for 24 months.
作者
窦颖辉
于晨阳
杨飞飞
李连连
廖永红
倪晓燕
DOU Yinghui;YU Chenyang;YANG Feifei;LI Lianlian;LIAO Yonghong;NI Xiaoyan(Anhui Anke Biotechnology(Group)Co.,Ltd,Hefei 230088,China;Institute of Medicinal Plant Development(IMPLAD),Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2024年第18期2496-2501,共6页
Chinese Journal of Modern Applied Pharmacy
基金
国家科技重大专项子课题(2011ZX09202-301)。
