title: In vivo lung deposition of hollow porous particles from a pressurized metered dose inhaler.
abstract: OBJECTIVE
  PulmoSphere particles are specifically engineered for delivery by the pulmonary route with a hollow and porous morphology, physical diameters < 5 microm, and low tap densities (circa 0.1 g x cm(-3)). Deposition of PulmoSphere particles in the human respiratory tract delivered by pressurized metered dose inhaler (pMDI) was compared with deposition of a conventional micronized drug pMDI formulation.
  
  
  METHODS
  Nine healthy nonsmoking subjects (5 male, 4 female) completed a two-way crossover gamma scintigraphic study, assessing the lung and oropharyngeal depositions of albuterol sulfate, formulated as 99mTc-radiolabeled PulmoSphere particles or micronized particles (Ventolin Evohaler, GlaxoSmithKline, Ltd.) suspended in HFA-134a propellant.
  
  
  RESULTS
  Mean (standard deviation) lung deposition, (% ex-valve dose) was doubled for the PulmoSphere formulation compared with Evohaler pMDI (28.5 (11.3) % vs. 14.5 (8.1) %, P < 0.01), whereas oropharyngeal deposition was reduced (42.6 (9.0) % vs. 72.0 (8.0) %, P < 0.01). Both PulmoSphere and Evohaler pMDIs gave uniform deposition patterns within the lungs.
  
  
  CONCLUSIONS
  These data provided "proof of concept" in vivo for the PulmoSphere technology as a method of improving targeting of drugs to the lower respiratory tract from pMDIs, and suggested that the PulmoSphere technology may also be suitable for the delivery of systemically acting molecules absorbed via the lung.
authors.affiliation: Pharmaceutical Profiles Ltd, Ruddington, Nottingham, United Kingdom. phirst@pharmprofiles.co.uk
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hirst
authors.forename: Gary R
authors.initials: GR
authors.lastname: Pitcairn
authors.forename: Jeff G
authors.initials: JG
authors.lastname: Weers
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Tarara
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Clark
authors.forename: Luis A
authors.initials: LA
authors.lastname: Dellamary
authors.forename: Gail
authors.initials: G
authors.lastname: Hall
authors.forename: Jolene
authors.initials: J
authors.lastname: Shorr
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Newman
mesh_terms: D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009330:Nebulizers and Vaporizers / Q000706:statistics & numerical data; D016062:Porosity; D018709:Statistics, Nonparametric; D005466:Fluorocarbons
chemical_list: D000420:Albuterol; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons