Pharmaceutical Research

, Volume 30, Issue 6, pp 1586–1596 | Cite as

Inhalable Powder Formulation of Pirfenidone with Reduced Phototoxic Risk for Treatment of Pulmonary Fibrosis

  • Satomi OnoueEmail author
  • Yoshiki Seto
  • Masashi Kato
  • Yosuke Aoki
  • Yoshiki Kojo
  • Shizuo Yamada
Research Paper



Orally-taken pirfenidone (PFD), an idiopathic pulmonary fibrosis drug, often causes severe phototoxicity. Present study aimed to develop a respirable powder formulation for PFD (PFD-RP) to minimize phototoxic risk.


Photochemical properties of PFD were examined using a reactive oxygen species (ROS) assay and photostability testing. PFD-RP was characterized with a focus on photostability, in vitro inhalation performance, and the efficacy in antigen-sensitized rats. Pharmacokinetic studies were conducted after oral and intratracheal administration of PFD formulations.


Although PFD solution exhibited photodegradation under simulated sunlight (250 W/m2), both PFD powder and PFD-RP were photochemically stable. Laser diffraction and cascade impactor analyses on PFD-RP suggested its high dispersion and fine in vitro inhalation performance. Inhaled PFD-RP (300 μg-PFD/rat) could suppress antigen-evoked pulmonary inflammation in rats as evidenced by decreases in recruited inflammatory cells and neutrophilia-related biomarkers in the lung. Exposure of PFD to light-exposed tissues (skin and eye) after intratracheal administration of PFD-RP at a pharmacologically effective dose (300 μg-PFD/rat) was 90–130-fold less than that of the oral PFD dosage form at a phototoxic dose (160 mg/kg).


PFD-RP might be an attractive alternative to the current oral PFD therapy with a better safety margin.

Key words

inhalation photostability phototoxicity pirfenidone pulmonary fibrosis 





analysis of variance


area under concentration versus time curve


area under moment curve


bronchoalveolar lavage fluid


eosinophil peroxidase


electrospray ionization mass spectrometry




hydroxypropyl methylcellulose




mean residence time




phosphate-buffered saline


reactive oxygen species


respirable powder


scanning electron microscopy




ultra performance liquid chromatography


Acknowledgments AND DISCLOSURES

Authors are grateful to Shionogi&Co., Ltd. for kindly providing pirfenidone. This work was supported in part by a Grant-in-Aid for Young Scientists (B) (No. 22790043; S. Onoue) from the Ministry of Education, Culture, Sports, Science, and Technology and a Health Labour Sciences Research Grant from The Ministry of Health, Labour, and Welfare, Japan.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Satomi Onoue
    • 1
    Email author
  • Yoshiki Seto
    • 1
  • Masashi Kato
    • 1
  • Yosuke Aoki
    • 1
  • Yoshiki Kojo
    • 1
  • Shizuo Yamada
    • 1
  1. 1.Department of Pharmacokinetics and Pharmacodynamics School of Pharmaceutical SciencesUniversity of ShizuokaShizuokaJapan

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