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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

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 

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)

REFERENCES

  1. 1.
    Hanania NA, Crater GD, Morris AN, Emmett AH, O’Dell DM, Niewoehner DE. Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. Respir Med. 2012;106(1):91–101.PubMedCrossRefGoogle Scholar
  2. 2.
    Sumby B, Cooper S, Smith I. A comparison of the inspiratory effort required to operate the Diskhaler inhaler and Turbohaler inhaler in the administration of powder drug formulations. Br J Clin Res. 1992;3:117–23.Google Scholar
  3. 3.
    Martonen B, Katz IM. Deposition patterns of aerosolised drugs within human lungs. Effects of ventilatory parameters. Pharm Res. 1993;10:871–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Chrystyn H. The Diskus™: a review of its position among dry powder inhaler devices. Int J Clin Pract. 2007;61(6):1022–36.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Chrystyn H, Niederlaender C. The Genuair inhaler: a novel, multi-dose dry powder inhaler. Int J Clin Pract. 2012;66(3):309–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Dunbar CA, Hickey AJ, Holder P. Dispersion and characterization of pharmaceutical dry powder aerosols. KONA Powder Part. 1998;16:45.Google Scholar
  7. 7.
    French DL, Edwards DA, Niven RW. The influence of formulation on emission, deaggregation and deposition of dry powders for inhalation. J Aerosol Sci. 1996;27:769–83.CrossRefGoogle Scholar
  8. 8.
    Voss A, Finlay WA. Deagglomeration of dry powder pharmaceutical aerosols. Int J Pharm. 2002;248(1–2):39–50.PubMedCrossRefGoogle Scholar
  9. 9.
    Burnell PK, Small T, Doig S, Johal B, Jenkins R, Gibson GJ. Ex-vivo product performance of Diskus™ and Turbuhaler inhalers using inhalation profiles from patients with severe chronic obstructive pulmonary disease. Respir Med. 2001;95(5):324–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Ganderton D. General factors influencing drug delivery to the lung. Respir Med. 1997;91:13.PubMedCrossRefGoogle Scholar
  11. 11.
    Palander A. In vitro comparison of three salbutamol-containing multidose dry powder inhalers. Clin Drug Invest. 2000;20:25–33.CrossRefGoogle Scholar
  12. 12.
    Rottier BL, Rubin BK. Asthma medication delivery: mists and myths. Paediatr Respir Rev. 2013;14(2):112–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Behara SR, Longest PW, Farkas DR, Hindle M. Development and comparison of new high-efficiency dry powder inhalers for carrier-free formulations. J Pharm Sci. 2014;103(2):465–77.Google Scholar
  14. 14.
    Melani AS, Zanchetta D, Barbato N, Sestini P, Cinti C, Canessa PA, et al. Inhalation technique and variables associated with misuse of conventional metered-dose inhalers and newer dry powder inhalers in experienced adults. Ann Allergy Asthma Immunol. 2004;93(5):439–46.PubMedCrossRefGoogle Scholar
  15. 15.
    Mahler DA, Waterman LA, Gifford AH. Prevalence and COPD phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus® dry powder inhaler. J Aerosol Med Pulm Drug Deliv. 2013;26(3):174–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Holmes M, Seheult J, Geraghty C, D’Arcy S, O’Brien U, Crispino O’Connell G, et al. A method of predicting inspiratory flow rate and volume from an inhaler using acoustic measurements. Physiol Meas. 2013;34:903–14.PubMedCrossRefGoogle Scholar
  17. 17.
    Fuller R. The Diskus™: a new multi-dose powder device -efficacy and comparison with Turbuhaler™. J Aerosol Med. 1995;8(2):11–7.Google Scholar
  18. 18.
    Mahler DA, Waterman LA, Ward J, Gifford AH. Comparison of dry powder versus nebulized beta-agonist in patients with COPD who have suboptimal peak inspiratory flow rate. J Aerosol Med Pulm Drug Deliv. 2014;27(2):103–9.Google Scholar
  19. 19.
    United States Pharmacopeial Convention (USP): Chapter 601: Aerosols, metered-dose inhalers, and dry powder inhalers. In: USP36-NF31. Rockville, MD: USP; 2013;242–262Google Scholar
  20. 20.
    Grasmeijer F, Hagedoorn P, Frijlink HW, de Boer AH. Characterisation of high dose aerosols from dry powder inhalers. Int J Pharm. 2012;437(1–2):242–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Hoe S, Young PM, Chan H-K, Traini D. Introduction of the electrical Next Generation Impactor (eNGI) and investigation of its capabilities for the study of pressurized metered dose inhalers. Pharm Res. 2009;26:431–7.PubMedCrossRefGoogle Scholar
  22. 22.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH, Q2 (R1). Geneva. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf, (2005). Accessed 4 Apr 2014.
  23. 23.
    International Organization for Standardization. ISO 27427. Anaesthetic and respiratory equipment— nebulizing systems and components. Geneva: International Standards Organization; 2010.Google Scholar
  24. 24.
    Inhalation Report, “How do you calculate MMAD,” (2010), www.inhalationreport.com, accessed 10 Nov. 2013
  25. 25.
    Du XL, Zhu Z, Fu Q, Li DK, Xu WB. Pharmacokinetics and relative bioavailability of salbutamol metered-dose inhaler in healthy volunteers. Acta Pharmacol Sin. 2002;23(7):663–6.PubMedGoogle Scholar
  26. 26.
    Brain JD. Mechanisms of aerosol deposition and clearance. In: Moren F, Newhouse MT, Dolovich MB, editors. Aerosols in medicine. Principles, diagnosis and therapy, 2nd edn. New York: Elsevier Science Publishers (Biomedical Division); 1993. p. 351–74.Google Scholar
  27. 27.
    Hossain I, Moussavi Z. Finding the lung sound-flow relationship in normal and asthmatic subjects. In proceeding of Engineering in Medicine and Biology Society, 2004. IEMBS '04. 26th Annual International Conference of the IEEE, Volume: 2, 1-5 September 2004. Sacramento, CA, USA. Conf Proc IEEE Eng Med Biol Soc. 2004;5:3852–5.Google Scholar
  28. 28.
    Edwards AM. Assessing lung deposition of inhaled medications. Consensus statement from a workshop of the British Association for Lung Research, held at the Institute of Biology, London, U.K. on 17 April 1998. Snell NJC, Ganderton D, eds. Respir Med 1999;93:123–33. Respir Med. 2000 Sep;94(9):918–9.Google Scholar

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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