In vivo lung deposition of hollow porous particles from a pressurized metered dose inhaler.
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.
Hirst
Peter H
PH
Pharmaceutical Profiles Ltd, Ruddington, Nottingham, United Kingdom. phirst@pharmprofiles.co.uk
Pitcairn
Gary R
GR
Weers
Jeff G
JG
Tarara
Thomas E
TE
Clark
Andrew R
AR
Dellamary
Luis A
LA
Hall
Gail
G
Shorr
Jolene
J
Newman
Stephen P
SP
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
D000420:Albuterol; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons