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Predicting the behavior of novel sugar carriers for dry powder inhaler formulations via the use of a cohesive–adhesive force balance approach

Authors

  • Jennifer C. Hooton,

    1. Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom
    Current affiliation:
    1. AstraZeneca R&D, Silk Road Business Park, Charter Way, Macclesfield, Cheshire, SK10 2NA, United Kingdom.
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  • Matthew D. Jones,

    1. Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom
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  • Robert Price

    Corresponding author
    1. Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom
    • Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom. Telephone: +44 1225 383644; Fax: +44 1225 386114
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Abstract

The aim of this work was to utilize the recently developed cohesive–adhesive balance (CAB) technique for analyzing quantitative AFM measurements to compare the relative forces of interaction of micronized salbutamol sulfate particles and a selection of specifically grown sugar substrates (β cyclodextrin, lactose, raffinose, trehalose and xylitol). The interfacial behavior was subsequently related to the in-vitro delivery performance of these sugars as carrier particles in dry powder inhalation (DPI) formulations. The CAB analysis indicated that the rank order of adhesion between salbutamol sulfate and the sugars was β cyclodextrin < lactose < trehalose < raffinose < xylitol. The β cyclodextrin was the only substrate with which salbutamol sulfate demonstrated a greater cohesive behavior. All other sugars exhibited an adhesive dominance. In-vitro deposition performance of the salbutamol sulfate based carrier DPI formulations showed that the rank order of the fine particle fraction (FPF) was β cyclodextrin > lactose > raffinose > trehalose > xylitol. A linear correlation (R2 = 0.9572) was observed between the FPF and cohesive–adhesive ratios of the AFM force measurements. The observed link between CAB analysis of the interactive forces and in-vitro performance of carrier based formulations suggested a fundamental understanding of the relative balance of the various forces of interaction within a dry powder formulation may provide a critical insight into the behavior of these formulations. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:1288–1297, 2006

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