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The use of colloid probe microscopy to predict aerosolization performance in dry powder inhalers: AFM and in vitro correlation

Authors

  • Paul M. Young,

    Corresponding author
    1. Pharmaceutical Technology Research Group, Department of Pharmacy, University of Bath, Bath, BA2 7AY, United Kingdom
    Current affiliation:
    1. Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
    • Pharmaceutical Technology Research Group, Department of Pharmacy, University of Bath, Bath, BA2 7AY, United Kingdom. Telephone: +61 2 9036 7035; Fax: +61 2 9351 4391
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  • Michael J. Tobyn,

    1. Pharmaceutical Technology Research Group, Department of Pharmacy, University of Bath, Bath, BA2 7AY, United Kingdom
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  • Robert Price,

    1. Pharmaceutical Technology Research Group, Department of Pharmacy, University of Bath, Bath, BA2 7AY, United Kingdom
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  • Mark Buttrum,

    1. Sanofi-Aventis, Holmes Chapel, Cheshire, CW4 8BE, United Kingdom
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  • Fiona Dey

    1. Sanofi-Aventis, Holmes Chapel, Cheshire, CW4 8BE, United Kingdom
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Abstract

The atomic force microscope (AFM) colloid probe technique was utilized to measure cohesion forces (separation energy) between three drug systems as a function of relative humidity (RH). The subsequent data was correlated with in vitro aerosolization data collected over the same RH range. Three drug-only systems were chosen for study; salbutamol sulphate (SS), triamcinolone acetonide (TAA), and di-sodium cromoglycate (DSCG). Analysis of the AFM and in vitro data suggested good correlations, with the separation energy being related inversely to the aerosolization performance (measured as fine particle fraction, FPFLD). In addition, the relationship between, cohesion, RH, and aerosolization performance was drug specific. For example, an increase in RH between 15% and 75% resulted in increased cohesion and decreased FPFLD for SS and DSCG. In comparison, for TAA, a decrease in cohesion and increased FPFLD was observed when RH was increased (15–75%). Linear regression analysis comparing AFM with in vitro data indicated R2 values > 0.80, for all data sets, suggesting the AFM could be used to indicate in vitro aerosolization performance. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1800–1809, 2006

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