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In Vivo Lung Deposition of Hollow Porous Particles from a Pressurized Metered Dose Inhaler

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Abstract

Purpose: PulmoSphere™ particles are specifically engineered for delivery by the pulmonary route with a hollow and porous morphology, physical diameters < 5 μm, and low tap densities (circa 0.1 g.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 EvohalerTM, 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.

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Authors and Affiliations

  1. Pharmaceutical Profiles Ltd, Mere Way, Ruddington Fields, Ruddington, Nottignham, NG11 6JS, United Kingdom

    Peter H. Hirst, Gary R. Pitcairn & Stephen P. Newman

  2. Inhale Therapeutic Systems, Inc., San Carlos, California, 94070

    Jeff G. Weers, Thomas E. Tarara & Andrew R. Clark

  3. Alliance Pharmaceutical Corp., San Diego, California, 02121

    Luis A. Dellamary, Gail Hall & Jolene Shorr

Authors
  1. Peter H. Hirst
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  2. Gary R. Pitcairn
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  3. Jeff G. Weers
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  4. Thomas E. Tarara
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  5. Andrew R. Clark
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  6. Luis A. Dellamary
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  7. Gail Hall
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  8. Jolene Shorr
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  9. Stephen P. Newman
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Correspondence to Peter H. Hirst.

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Hirst, P.H., Pitcairn, G.R., Weers, J.G. et al. In Vivo Lung Deposition of Hollow Porous Particles from a Pressurized Metered Dose Inhaler. Pharm Res 19, 258–264 (2002). https://doi.org/10.1023/A:1014482615914

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