Heterogeneous particle deaggregation and its implication for therapeutic aerosol performance

Authors

  • Zhen Xu,

    1. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Kerr Hall, Chapel Hill, North Carolina 27599-7360
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  • Heidi M. Mansour,

    1. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Kerr Hall, Chapel Hill, North Carolina 27599-7360
    Current affiliation:
    1. Drug Development Division, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536-0082.
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  • Tako Mulder,

    1. DMV-Fonterra Excipients, Goch, Nordrhein-Westfalen, Germany
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  • Richard McLean,

    1. Pfizer, Inc., Sandwich, Kent, UK
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  • John Langridge,

    1. DMV-Fonterra Excipients, Goch, Nordrhein-Westfalen, Germany
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  • Anthony J. Hickey

    Corresponding author
    1. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Kerr Hall, Chapel Hill, North Carolina 27599-7360
    • Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Kerr Hall, Chapel Hill, North Carolina 27599-7360. Telephone: 919-962-0223; Fax: 919-966-0197.
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Abstract

Aerosolization performance of dry powder blends of drugs for the treatment of asthma or chronic obstructive pulmonary diseases have been reported in three previous articles. In vitro aerosolization was performed at defined shear stresses (0.624–13.143 N/m2). Formulations were characterized aerodynamically and powder aerosol deaggregation equations (PADE) and corresponding linear regression analyses for pharmaceutical aerosolization were applied. Particle deaggregation is the result of overcoming fundamental forces acting at the particle interface. A new method, PADE, describing dry powder formulation performance in a shear stress range has been developed which may allow a fundamental understanding of interparticulate and surface forces. The application of PADE predicts performance efficiency and reproducibility and supports rational design of dry powder formulations. The analogy of aerosol performance with surface molecular adsorption has important implications. Expressions describing surface adsorption were intended to allow elucidation of mechanisms involving surface heterogeneity, lateral interaction, and multilayer adsorption of a variety of materials. By using a similar expression for drug aerosolization performance, it is conceivable that an analogous mechanistic approach to the evaluation of particulate systems would be possible. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3442–3461, 2010

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