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The Acoustic Features of Inhalation can be Used to Quantify Aerosol Delivery from a Diskus™ Dry Powder Inhaler

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ABSTRACT

Purpose

Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery.

Methods

A sensitivity analysis of the relationship of the acoustics of inhalation to simultaneously recorded airflow, in a cohort of volunteers (n = 92) was performed. The Next Generation Impactor (NGI) was used to assess in vitro drug delivery from salmeterol/fluticasone and salbutamol Diskus™ DPIs. Fine particle fraction, FPF, (<5 μm) was measured at 30–90 l/min for 2–6 s and correlated with acoustically determined flow rate (IFRc). In pharmacokinetic studies using a salbutamol (200 μg) Diskus™, volunteers inhaled either at maximal or minimal effort on separate days.

Results

PIFRc was correlated with spirometrically determined values (R 2 = 0.88). In in vitro studies, FPF increased as both flow rate and inhalation duration increased for the salmeterol/fluticasone Diskus™ (Adjusted R 2 = 0.95) and was proportional to flow rate only for the salbutamol Diskus™ (Adjusted R 2 = 0.71). In pharmacokinetic studies, blood salbutamol levels measured at 20 min were significantly lower when PIFRc was less than 60 l/min, p < 0.0001.

Conclusion

Acoustically-determined PIFR is a suitable method for estimating drug delivery and for monitoring inhalation technique over time.

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was primarily funded by an HRB Ireland CSA Research Grant 12/1533. POC and AMH acknowledge funding from Science Foundation Ireland under Grant Nos. 08/CE/I1432, 07/SRC/B1158 and 12/RC/2275. The authors of this paper would also like to thank Vitalograph Ltd and GlaxoSmithKline Ltd for generously providing financial support for this study. We would like to thank the volunteers and patients who participated in the studies and the internal and external staff involved

The patented acoustic device [INCA™] used in this study is manufactured by Vitalograph, Ireland. The first authors of this paper have no affiliation to Vitalograph and are not listed as a holder of the relevant patents. RBR, SD and RWC are listed on the patents.

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Authors and Affiliations

  1. Department of Medicine Respiratory Research Division, Royal College of Surgeons in Ireland, Dublin, Ireland

    Jansen N. Seheult, Kee Chun Tee, Tariq Bholah, Hasan Al Bannai, Imran Sulaiman, Elaine MacHale, David Bergin, Emer Reeves & Richard W. Costello

  2. School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland

    Peter O’Connell, Carsten Ehrhardt & Anne Marie Healy

  3. Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland

    Shona D’Arcy, Martin S. Holmes & Richard B. Reilly

  4. Statistica Medica, Dublin, Ireland

    Gloria Crispino-O’Connell

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  1. Jansen N. Seheult
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  2. Peter O’Connell
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Corresponding author

Correspondence to Jansen N. Seheult.

Additional information

Jansen N. Seheult and Peter O’Connell: These authors contributed equally to this work.

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Seheult, J.N., O’Connell, P., Tee, K.C. et al. The Acoustic Features of Inhalation can be Used to Quantify Aerosol Delivery from a Diskus™ Dry Powder Inhaler. Pharm Res 31, 2735–2747 (2014). https://doi.org/10.1007/s11095-014-1371-x

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  • DOI: https://doi.org/10.1007/s11095-014-1371-x

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