title: Carrier-free high-dose dry powder inhaler formulation of ibuprofen: Physicochemical characterization and in vitro aerodynamic performance.
abstract: OBJECTIVE
  To investigate influences of capsule fill weight, batch size, and storage conditions on in vitro aerodynamic performance of jet-milled ibuprofen (IBU) carrier-free, dry powder inhaler formulations.
  
  
  METHODS
  Milled and unmilled IBU samples were characterized thermally and spectroscopically. Physicochemical characterization was performed by quantifying specific surface area, density, and angle of repose. Performance testing was conducted on IBU formulations in combination with a high resistance Monodose RS01 using Next Generation Impactor.
  
  
  CONCLUSIONS
  There were no detectable differences between IBU samples thermally and spectroscopically. The milled IBU sample exhibited improved powder flow in comparison with the unmilled sample. The milled IBU powders possessed surprisingly high in vitro aerodynamic performance with a fine particle fraction percentage between 67 and 85%, and a minimum respirable fraction percentage of 49%. The capsule fill weights, from 10 to 50mg, and milling batch sizes did not significantly influence performance. The importance of powder conditioning following milling was illustrated as the storage duration and temperature negatively affected performance.
  
  
  CONCLUSIONS
  In vitro aerodynamic performance of IBU is independent of capsule fill weight and batch size; however, some period of powder conditioning is recommended to reduce variability in formulation performance.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, PHR 4.214, 2409 University Ave, A1920, Austin, TX 78712-1119, USA.
authors.forename: Ashkan K
authors.initials: AK
authors.lastname: Yazdi
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, PHR 4.214, 2409 University Ave, A1920, Austin, TX 78712-1119, USA. Electronic address: hugh.smyth@austin.utexas.edu.
authors.forename: Hugh D C
authors.initials: HDC
authors.lastname: Smyth
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004304:Dosage Forms; D058995:Dry Powder Inhalers / Q000379:methods*; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D007052:Ibuprofen
keywords: Capsule fill weight; Conditioning period; Ibuprofen (PubChem CID: 3672); Jet milling; Next generation impactor; Storage temperature; Tween 20 (PubChem CID: 443314); sodium dodecyl sulfate (PubChem CID: 3423265)