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  • 标题:Study of pH Stability of R-Salbutamol Sulfate Aerosol Solution and Its Antiasthmatic Effects in Guinea Pigs
  • 本地全文:下载
  • 作者:Qing Liu ; Qingrui Li ; Ting Han
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2017
  • 卷号:40
  • 期号:9
  • 页码:1374-1380
  • DOI:10.1248/bpb.b17-00067
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Currently, all commercial available nebulized salbutamol in China is in its racemic form. It is known that only R -salbutamol (eutomer) has therapeutic effects, while S -salbutamol (distomer) may exacerbate asthma after chronic use. Therefore, it is an unmet clinical need to develop R -salbutamol as a nebulized product that is more convenient for young and old patients. In our study, a stable aerosol solution of R -salbutamol sulfate was established, and its antiasthmatic effects were confirmed. The decomposition rate and racemization effect of the R -salbutamol sulfate solution were evaluated over a pH range from 1 to 10 (except pH=7, 8) at 60°C. The aerodynamic particle size of the R -salbutamol sulfate solution and commercial RS -salbutamol sulfate solution were both tested in vitro by Next-Generation Impactor (NGI) in 5°C. Laser diffractometer was used to characterize the droplet-size distribution (DSD) of both solutions. We next conducted an in vivo animal study to document the antiasthmatic effect of R -salbutamol aerosol sulfate solution and determine the relationship to RS -salbutamol. The results showed that the R -salbutamol sulfate solution was more stable at pH 6. In vitro comparison studies indicated that there was no distribution difference between R -salbutamol sulfate solution and the commercial RS -salbutamol solution. The animal results showed that R -salbutamol was more potent than RS -salbutamol against the same dose of histamine challenge. Unlike commercial RS -salbutamol, which was acidified to a pH of 3.5 to extend bench life but may cause bronchoconstriction in asthmatic patients, the neutralized R -salbutamol solution was more suitable for clinic use.

  • 关键词:R-salbutamol sulfate;pH stability;nebulization;particle size;antiasthma effect
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