title: Development of an Improved Inhalable Powder Formulation of Pirfenidone by Spray-Drying: In Vitro Characterization and Pharmacokinetic Profiling.
abstract: Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method.
  
  
  
  Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations.
  
  
  
  Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose.
  
  
  
  SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Suzuki
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Sharon Shui Yee
authors.initials: SS
authors.lastname: Leung
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002853:Chromatography, Liquid; D003890:Desiccation; D004195:Disease Models, Animal; D004339:Drug Compounding; D008297:Male; D010047:Ovalbumin; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D011208:Powders; D011728:Pyridones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000336:Aerosols; D000893:Anti-Inflammatory Agents; D011208:Powders; D011728:Pyridones; D010047:Ovalbumin; C093844:pirfenidone; D009195:Peroxidase
keywords: inhalation; pirfenidone; pulmonary fibrosis; spray dry; systemic exposure