Skip to main content
SpringerLink
Log in

Plume Characteristics of Two HFA-Driven Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combination Pressurized Metered-Dose Inhalers

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

New inhalers propelled by hydrofluoroalkanes (HFAs) have improved plume characteristics: higher fine particle fraction, and warmer plumes with reduced force and velocity. Together, this may avoid reflex interruption of inhalation and improve lung deposition of the inhaled drugs. However, even with HFA-propelled pressurized metered-dose inhalers (pMDIs), there are notable differences in device properties. Here we compared the duration, velocity, force, and temperature of two inhaled corticosteroid/long-acting β2-agonist combination therapies, administered via HFA pMDIs: fluticasone propionate/formoterol 125/5 µg (FP/FORM; flutiform®) and fluticasone propionate/salmeterol 125/25 µg (FP/SAL; Seretide® Evohaler®).

Methods

Inhalers were fired into ambient air. Plume duration and velocity were recorded with a high-speed camera and a pulsed laser light source. A copper disc attached to a sensitive load cell measured the plume force at various distances from the device. A thermal imaging video camera recorded impaction temperature in line with the device.

Results

The average plume duration for FP/FORM was longer than that of FP/SAL: 168.3 vs. 114.0 ms, respectively. The mean maximum plume velocities observed at 95 mm (the approximate distance between mouthpiece and throat) was consistently slower for FP/FORM (10.08 m/s) compared to FP/SAL (15.55 m/s). FP/FORM had a slower velocity at the outset, remaining relatively constant before declining steadily over the plume duration. The force of the FP/SAL plume was greater than that of FP/FORM at all distances: maximum force for FP/FORM was 138.2 vs. 278.9 mN for FP/SAL. The minimum impaction temperature was +5.9 °C for FP/FORM and −37.8 °C for FP/SAL; this difference became less pronounced over distance.

Conclusion

There were substantial differences between the plumes of the two pMDIs. FP/FORM was warmer, less forceful, had a longer plume duration and slower maximal velocity. These plume characteristics of FP/FORM may lead to improved lung deposition.

Funding

Mundipharma Research Limited, Cambridge, UK.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Gabrio BJ, Stein SW, Velasquez DJ. A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers. Int J Pharm. 1999;186:3–12.

    Article  CAS  PubMed  Google Scholar 

  2. Leach CL. The CFC to HFA transition and its impact on pulmonary drug development. Respir Care. 2005;50(9):1201–8.

    PubMed  Google Scholar 

  3. Leach C, Davidson P, Boudreau R. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J. 1998;12(6):1346–53.

    Article  CAS  PubMed  Google Scholar 

  4. Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Lung deposition of HFA-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorcarbon beclomethasone: a cross-over study in healthy volunteers. Chest. 2002;122(2):510–6.

    Article  CAS  PubMed  Google Scholar 

  5. Pedersen S, Frost L, Arnfred T. Errors in inhalation technique and efficiency in inhaler use in asthmatic children. Allergy. 1986;41:118–24.

    Article  CAS  PubMed  Google Scholar 

  6. Crompton GK. Problems patients have using pressurized aerosol inhalers. Eur J Respir Dis. 1982;Suppl 119:57–65.

  7. Newman S, Weisz AWB, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. Thorax. 1991;46:712–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Johal B, Howald M, Fischer M, Marshall J, Venthoye G. Fine particle profile of fluticasone propionate/formoterol fumarate versus other combination products: the DIFFUSE study. Comb Prod Ther. 2013;3(1–2):39–51.

    Article  Google Scholar 

  9. Newman S. Principles of metered-dose inhaler design. Respir Care. 2005;50(9):1177–99.

    PubMed  Google Scholar 

  10. Bell D, Mansfield L, Lomax M, Dissanayake S. Fluticasone/formoterol pressurized metered-dose inhaler: an assessment of patient preference and usability in adolescent and adult patients with obstructive lung disease. Respir Drug Deliv Europe. 2015;2:239–44.

    Google Scholar 

  11. McCabe JC, Koppenhagen F, Blair J, Zeng XM. ProAir(R) HFA delivers warmer lower-impact, longer-duration plumes containing higher fine particle dose than Ventolin(R) HFA. J Aerosol Med Pulm Drug Deliv. 2012;25(2):104–9.

    Article  CAS  PubMed  Google Scholar 

  12. Brambilla G, Church T, Lewis D, Meakin B. Plume temperature emitted from metered dose inhalers. Int J Pharm. 2011;405(1–2):9–15.

    Article  CAS  PubMed  Google Scholar 

  13. Crosland BM, Johnson MR, Matida EA. Characterization of the spray velocities from a pressurized metered-dose inhaler. J Aerosol Med Pulm Drug Deliv. 2009;22(2):85–98.

    Article  PubMed  Google Scholar 

  14. Nicolini G, Scichilone N, Bizzi A, Papi A, Fabbri L. Beclomethasone/formoterol fixed combination for the management of asthma: patient considerations. Ther Clin Risk Mgt. 2008;4(5):855–64.

    CAS  Google Scholar 

  15. Lewis DA, Johnson S, Meakin BJ, Ganderton D, Brambilla G, Garzia R, et al. Effects of actuator orifice diameter on beclomethasone dipropionate delivery from a pMDI HFA solution formulation. In: Byron PR, Dalby RN, Farr SJ, editors. Respiratory Drug Delivery VI; 1998 3–7 May; Hilton Head, South Carolina. Interpharm Press, Buffalo, IL; 1998. p. 363–4.

  16. Laube BL, Janssens HM, de Jongh FHC, Devadason SG, Dhand R, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011;37:1308–31.

    Article  CAS  PubMed  Google Scholar 

  17. Brand P, Hederer B, Austen G, Dewberry H, Meyer T. Higher lung deposition with Respimat(R) Soft Mist(TM) inhaler than HFA-MDI in COPD patients with poor technique. Int J COPD. 2008;3(4):763–70.

    CAS  Google Scholar 

  18. Newman SP, Brown J, Steed KP, Reader SJ, Kladders H. Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices. Chest. 1998;113:957–63.

    Article  CAS  PubMed  Google Scholar 

  19. Haussermann S, Acerbi D, Brand P, Herpich C, Poli G, Sommerer K, Meyer T. Lung deposition of formoterol HFA (Atimos/Forair) in healthy volunteers, asthmatic and COPD patients. J Aerosol Med. 2007;20:331–41.

    Article  PubMed  Google Scholar 

  20. Newman SP. Spacer devices for metered dose inhalers. Clin Pharmacokinetics. 2004;43:349–60.

    Article  Google Scholar 

  21. Price DB, Ryan D, Gruffydd-Jones K, Haughney J, et al. Assessment of potentially important device errors performed by asthma patients in the global iHARP review service. Abstract presented at the IPCRG 2014 Congress, Athens, Greece 21–24 May.

  22. Lavorini F. The challenge of delivering therapeutic aerosols to asthma patients. ISRN Allergy. 2013;2013:ID 102418.

  23. Price D, Papi A, Kaiser K, Grothe B, Lomax M. Fluticasone propionate/formoterol fumarate combination therapy is equally effective and well-tolerated when administered with or without a spacer device to patients with asthma. Eur Respir J. 2011;38(Suppl 55):3986.

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank Jude Douglass of Healthcom Partners Limited and Evelin Kozma from Mundipharma Research Limited for Medical Writing assistance. This study, including Medical Writing assistance, and article publication charges, was funded by Mundipharma Research Limited, Cambridge, UK.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Data from this study have been presented previously as two abstracts at the Annual Congress of the European Respiratory Society (Johal B, Murphy S, Marshall J. Plume characteristics of fluticasone propionate/formoterol pMDI compared with fluticasone propionate/salmeterol pMDI. ERJ 2013;42(Suppl 57):4132., and Johal B, Tuohy J, Marshall J. Plume temperature and force of fluticasone propionate/formoterol pMDI compared with fluticasone propionate/salmeterol pMDI. ERJ 2014;44(Suppl 58):Abstract 955).

®FLUTIFORM is a registered trademark of Jagotec AG and is used under license.

®SERETIDE and EVOHALER are registered trademarks of Glaxo Group Limited.

Conflict of interest

Baljinder Johal is an employee of Mundipharma Research Limited; Seamus Murphy and John Tuohy declare that they have no conflicts of interest, and Jonathan Marshall is an employee of Mundipharma International Ltd. flutiform ® is distributed under license from Jagotec AG by independent associated companies of Mundipharma Research Limited.

Compliance with ethics guidelines

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Mundipharma Research Ltd, Unit 191, Cambridge Science Park, Milton Road, Cambridge, CB4 0GW, UK

    Baljinder Johal

  2. Oxford Lasers Ltd, Unit 8, Moorbrook Park, Didcot, Oxon, OX11 7HP, UK

    Séamus Murphy

  3. Prior PLM Medical, IDA Business and Technology Park, Carrick-on-Shannon, Co., Leitrim, Ireland

    John Tuohy

  4. Mundipharma International Ltd, Unit 194, Cambridge Science Park, Milton Road, Cambridge, CB4 0AB, UK

    Jonathan Marshall

Authors
  1. Baljinder Johal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Séamus Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Tuohy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonathan Marshall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Baljinder Johal.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 301 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johal, B., Murphy, S., Tuohy, J. et al. Plume Characteristics of Two HFA-Driven Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combination Pressurized Metered-Dose Inhalers. Adv Ther 32, 567–579 (2015). https://doi.org/10.1007/s12325-015-0219-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-015-0219-z

Keywords

Search

Navigation