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Pharmaceutical Dry Powder Aerosols: Correlation of Powder Properties with Dose Delivery and Implications for Pharmacodynamic Effect

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Abstract

Purpose. Efficient dispersion of bulk solids is critical for dry powder aerosol production which can be viewed as a sequence of events from stationary through dilated, flowing and finally dispersed particulates. The purpose of this study was to test the hypothesis that numerical descriptors of powder flow properties predict aerosol dispersion and pharmacodynamic effect.

Methods. Drug and excipient particles were prepared in size ranges suitable for inhalation drug delivery, and their physico-chemical properties were evaluated. Novel techniques (chaos analysis of dynamic angle of repose and impact force separation) were developed and utilized to measure and characterize powder flow and particle detachment from solid surfaces, respectively. Dry powder aerosol dispersion was evaluated using inertial impaction. Pharmacodynamic evaluations of bronchodilation were performed in guinea pigs, for selected formulations.

Results. We observed a direct correlation of powder flow with ease of particle separation (r2 = 0.9912) and aerosol dispersion (r2 = 0.9741). In vivo evaluations indicated that formulations exhibiting a higher in vitro dose delivery resulted in a greater reduction in pulmonary inflation pressure.

Conclusions. These results integrate powder behavior at various levels and indicate that numerical descriptors of powder flow accurately predict dry powder aerosol dispersion. A proportionality between aerosol dispersion and pharmacodynamic effect was observed in preliminary in vivo evaluations, which demonstrates the potential of these techniques for correlation studies between in vitro powder properties and in vivo effect.

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Author notes

  1. Neville M. Concessio

    Present address: Pharmaceutical Division, Biotechnology, Bayer Corporation, 800 Dwight Way, Berkeley, California, 94710

Authors and Affiliations

  1. Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599

    Neville M. Concessio & Anthony J. Hickey

  2. Inhalation Product Development, GlaxoWellcome Inc., RTP, North Carolina, 27709

    Michiel M. VanOort

  3. Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina, 27599

    Michael R. Knowles

Authors
  1. Neville M. Concessio
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  2. Michiel M. VanOort
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  3. Michael R. Knowles
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  4. Anthony J. Hickey
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Correspondence to Neville M. Concessio.

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Concessio, N.M., VanOort, M.M., Knowles, M.R. et al. Pharmaceutical Dry Powder Aerosols: Correlation of Powder Properties with Dose Delivery and Implications for Pharmacodynamic Effect. Pharm Res 16, 828–834 (1999). https://doi.org/10.1023/A:1018865717374

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  • DOI: https://doi.org/10.1023/A:1018865717374

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