Pharmaceutical Research

, Volume 31, Issue 10, pp 2735–2747 | Cite as

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

  • Jansen N. Seheult
  • Peter O’Connell
  • Kee Chun Tee
  • Tariq Bholah
  • Hasan Al Bannai
  • Imran Sulaiman
  • Elaine MacHale
  • Shona D’Arcy
  • Martin S. Holmes
  • David Bergin
  • Emer Reeves
  • Richard B. Reilly
  • Gloria Crispino-O’Connell
  • Carsten Ehrhardt
  • Anne Marie Healy
  • Richard W. Costello
Research Paper
First Online:
Received:
Accepted:

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.

KEY WORDS

aerosol delivery asthma cascade impactor COPD inhaler technique 
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Notes

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.

Supplementary material

11095_2014_1371_MOESM1_ESM.docx (139 kb)
ESM 1 (DOCX 139 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jansen N. Seheult
    • 1
  • Peter O’Connell
    • 2
  • Kee Chun Tee
    • 1
  • Tariq Bholah
    • 1
  • Hasan Al Bannai
    • 1
  • Imran Sulaiman
    • 1
  • Elaine MacHale
    • 1
  • Shona D’Arcy
    • 3
  • Martin S. Holmes
    • 3
  • David Bergin
    • 1
  • Emer Reeves
    • 1
  • Richard B. Reilly
    • 3
  • Gloria Crispino-O’Connell
    • 4
  • Carsten Ehrhardt
    • 2
  • Anne Marie Healy
    • 2
  • Richard W. Costello
    • 1
  1. 1.Department of Medicine Respiratory Research DivisionRoyal College of Surgeons in IrelandDublinIreland
  2. 2.School of Pharmacy and Pharmaceutical SciencesPanoz Institute, Trinity College DublinDublinIreland
  3. 3.Trinity Centre for BioengineeringTrinity College DublinDublinIreland
  4. 4.Statistica MedicaDublinIreland

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