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Optical diagnostics study of air flow and powder fluidisation in Nexthaler (R)-Part I: Studies with lactose placebo formulation

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journal contribution
posted on 18.02.2016 by I. Pasquali, C. Merusi, G. Brambilla, Edward Long, Graham Hargrave, Hendrik Versteeg
Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler® is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into “transparent “ Nexthalers® to allow application of high speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (~20 ms) after withdrawal of the dose protector followed by powder emission from the device within ~50 ms thereafter. The bulk of the metered placebo dose was emitted within 100-200 ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler® DPI will be very beneficial for carrier-drug de-aggregation.

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

INTERNATIONAL JOURNAL OF PHARMACEUTICS

Volume

496

Issue

2

Pages

780 - 791 (12)

Citation

PASQUALI, I. ...et al., 2015. Optical diagnostics study of air flow and powder fluidisation in Nexthaler (R)-Part I: Studies with lactose placebo formulation. International Journal of Pharmaceutics, 496(2), pp. 780-791.

Publisher

© Elsevier

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2015

Notes

This paper was accepted for publication in International Journal of Pharmaceutics and the definitive published version is available at http://dx.doi.org/10.1016/j.ijpharm.2015.10.072.

ISSN

0378-5173

Language

en

Exports