Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate

Authors

  • Zhen Xu,

    1. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Kerr Hall, Chapel Hill, NC 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, NC 27599-7360
    Current affiliation:
    1. College of Pharmacy, Drug Development Division, 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, NC 27599-7360
    • Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Kerr Hall, Chapel Hill, NC 27599-7360. Telephone: 919-962-0223; Fax: 919-966-0197.
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Abstract

The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (τs), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 µm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (τs = 0.624 N/m2) gave a higher emitted dose (ED ∼ 84–93%) and lower FPF (FPF6.4 ∼ 7–25%). In contrast, the highest shear SET (τs = 13.143 N/m2) gave a lower ED (ED ∼ 75–89%) and higher FPF (FPF6.4 ∼ 15–46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given τs, as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R2 ∼ 0.9804–0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3398–3414, 2010

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