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Aerosol Dispersion of Respirable Particles in Narrow Size Distributions Produced by Jet-Milling and Spray-Drying Techniques

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Abstract

Purpose. To examine the effect of particle size and morphology on aerosol dispersion using jet-milled and spray-dried mannitol particles in narrow size distributions within the respirable range.

Methods. Particle size and morphology were examined by laser diffraction and scanning electron microscopy, respectively. Aerosol dispersion was examined using a cascade impactor with a preseparator operating at a flow rate of 60 L/min, using two inhaler devices: Rotahaler (low-resistance device) and Inhalator (high-resistance device). Powder flow was examined using static and dynamic methods (Carr's compressibility index and vibrating spatula, respectively).

Results. Narrow size distributions of jet-milled and spray-dried particles were produced (d50% = 1.4 to 10.3 μm, GSD = 1.8 to 2.1, and d50% = 1.6 to 7.5 μm; GSD = 1.5 to 1.9, respectively). All particles were highly crystalline. Differences in particle shape were observed between jet-milled and spray-dried particles. Higher fine particle fraction (FPF) and relative fine particle fraction (FPFrel) (greater aerosol dispersion) and lower geometric standard deviation (GSD) (less variation) were obtained using particles with d50% between 2 and 5 μm. Higher mass median aerodynamic diameter were obtained with larger d50%. Spray-dried particles produced greater aerosol dispersion compared with jet-milled particles. Greater aerosol dispersion was obtained using the Inhalator than the Rotahaler.

Conclusions. Small changes in the particle size within the 1-10-μm range produced a major impact in the aerosol dispersion of jet-milled and spray-dried particles. Even in these narrow size ranges, aggregation plays an important role in aerosol dispersion.

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Author notes

  1. Margaret D. Louey

    Present address: Inhalation Product Development, GlaxoSmithKline, Research Triangle Park, North Carolina, 27709, USA

Authors and Affiliations

  1. Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Margaret D. Louey & Anthony J. Hickey

  2. Inhalation Product Development, GlaxoSmithKline, Research Triangle Park, North Carolina, 27709, USA

    Michiel Van Oort

Authors
  1. Margaret D. Louey
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  2. Michiel Van Oort
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  3. Anthony J. Hickey
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Correspondence to Anthony J. Hickey.

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Louey, M.D., Van Oort, M. & Hickey, A.J. Aerosol Dispersion of Respirable Particles in Narrow Size Distributions Produced by Jet-Milling and Spray-Drying Techniques. Pharm Res 21, 1200–1206 (2004). https://doi.org/10.1023/B:PHAM.0000033007.27278.60

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  • DOI: https://doi.org/10.1023/B:PHAM.0000033007.27278.60

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