Skip to main content
SpringerLink
Log in

In Vitro Comparison of Output and Particle Size Distribution of Budesonide from Metered-Dose Inhaler with Three Spacer Devices during Pediatric Tidal Breathing

  • Original Research Article
  • Published:
Treatments in Respiratory Medicine

Abstract

Objectives: The aim of this in vitro study was to determine the delivered dose of budesonide 200μg via a chlorofluorocarbon-free pressurized metered dose inhaler (pMDI) when administered through different spacers in tidal breathing patterns of young children.

Methods: Tidal breathing was simulated for toddlers and children. Spacers tested were Babyhaler®, AeroChamber® Plus small and medium; the pMDI was Budiair® 200μg. Output was measured after one actuation and five inhalations in primed and unprimed spacers. Cumulated output was evaluated after each of five simulated inhalations. Aerosol characteristics — i.e. particle size distribution of the output — were determined in primed spacers with a cascade impactor using high-performance liquid chromatography and UV detection.

Results: Total output from primed spacers after five inhalations was determined between 37.9μg and 40.9μg with little differences between spacers and breathing patterns. About 58–79% of this total output was inhaled with the first breath from the AeroChamber® Plus and about 26% from the Babyhaler®. The fine particles <5μm ranged between 87% and 92% of the delivered dose for all three spacers.

Discussion and Conclusion: The nominal dose (200μg) of the Budiair® 200μg inhaler is reduced to 40μg delivered dose or less by using Babyhaler® and AeroChamber® Plus spacers taking five breaths. With a single breath the delivered dose can be reduced further to a minimum of 10μg using the Babyhaler®. Clinical studies are warranted in the future for decisions on ’clinical efficacy’, safety, and exact dose adjustment.

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
Table I
Fig. 2
Table II
Table III

Similar content being viewed by others

Notes

  1. 1 The use of trade names is for product identification purposes only and does not imply endorsement.

  2. 2 Outside the spacer: 40% of the nominal dose pass the spacer and 90% of these particles are smaller than 4.9μm (= respirable fraction.)

References

  1. Ross DL, Schultz RK. Effect of inhalation flow rate on the dosing characteristics of dry powder inhaler (DPI) and metered dose inhaler (MDI) products. J Aerosol Med 1996; 9: 215–26

    Article  PubMed  CAS  Google Scholar 

  2. Smith KJ, Chan HK, Brown KF. Influence of flow rate on aerosol particle size distributions from pressurized and breath-actuated inhalers. J Aerosol Med 1998; 11: 231–45

    Article  PubMed  CAS  Google Scholar 

  3. Everard ML, Devadason SG, LeSouéf PN. Flow early in the inspiratory maneuver affects the aerosol particle size distribution from a Turbohaler. Respir Med 1997; 91: 624–8

    Article  PubMed  CAS  Google Scholar 

  4. Leach CL. Improved delivery of inhaled steroids to the large and small airways. Respir Med 1998; 92: 3–8s

    Article  PubMed  Google Scholar 

  5. Feddah MR, Davies NM, Gipps EM, et al. Influence of respiratory spacer devices on aerodynamic particle size distribution and fine particle mass of beclomethasone from metered-dose inhalers. J Aerosol Med 2001; 14: 477–85

    Article  PubMed  CAS  Google Scholar 

  6. Asmus MJ, Liang J, Coowanitwong I, et al. In vitro performance characteristics of valved holding chamber and spacer devices with a fluticasone metered-dose inhaler. Pharmacotherapy 2004; 24: 159–66

    Article  PubMed  CAS  Google Scholar 

  7. Terzano C, Mannino F. Aerosol characterization of three corticosteroid metered dose inhalers with volumatic holding chambers and metered dose inhalers alone at two inspiratory flow rates. J Aerosol Med 1999; 12: 249–54

    Article  PubMed  CAS  Google Scholar 

  8. Janssens HM, Krijgsman A, Verbraak TFM, et al. Determining factors of aerosol deposition for four pMDI-Spacer combinations in an infant upper airway model. J Aerosol Med 2004; 17: 51–61

    Article  PubMed  CAS  Google Scholar 

  9. Everard ML, Clark AR, Milner AD. Drug delivery from holding chambers with attached facemask. Arch Dis Child 1992; 67: 580–5

    Article  PubMed  CAS  Google Scholar 

  10. Mitchell JP, Nagel MW. In vitro performance testing of three small volume-holding chambers under conditions that correspond with use by infants and small children. J Aerosol Med 1997; 10: 341–9

    Article  PubMed  CAS  Google Scholar 

  11. Berg E, Madsen J, Bisgaard H. In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children. Eur Respir J 1998; 12: 472–6

    Article  PubMed  CAS  Google Scholar 

  12. Finlay WH, Zuberbuhler P. In vitro comparison of beclomethasone and salbutamol metered-dose inhaler aerosols inhaled during pediatric tidal breathing from four valved holding chambers. Chest 1998; 114: 1676–80

    Article  PubMed  CAS  Google Scholar 

  13. Barry PW, O’Callaghan C. The output of budesonide from spacer devices assessed under simulated breathing conditions. J Allergy Clin Immunol 1999; 104: 1205–10

    Article  PubMed  CAS  Google Scholar 

  14. Janssens HM, De Jongste JC, Hop WC, et al. Extra-fine particles improve lung delivery of inhaled steroids in infants: a study in an upper airway model. Chest 2003; 123: 2083–8

    Article  PubMed  CAS  Google Scholar 

  15. Usmani OS, Biddiscombe MF, Nightingale JA, et al. Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols. J Appl Physiol 2003; 95: 2106–12

    PubMed  Google Scholar 

  16. Ganderton D, Lewis D, Davies R, et al. The formulation and evaluation of CFC-free budesonide pressurized metered dose inhaler. Respir Med 2003; Suppl. D: S4–9

  17. US Pharmacopeia. Physical tests and determinations: aerosols. Rockville (MD): United States Pharmacopeia, USP Convention Inc., 2nd Supplement 2003; chapter 601: 2105–23

    Google Scholar 

  18. Berg E, Asking L, Svensson JO. Is it possible to measure the particle size distribution from a pMDI/spacer during simulated breathing? Eur Respir J 1997; 10: 81s

    Google Scholar 

  19. O’Callaghan C, Lynch J, Robertson C. Improvement in sodium chromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug. Thorax 1993; 48: 603–6

    Article  PubMed  Google Scholar 

  20. Council of Europe. Preparations for inhalation: aerodynamic assessment of fine particles. European Pharmacopoeia 2002, Council of Europe, Strasbourg, France. 3rd Supplement 2001: 113–24

    Google Scholar 

  21. Kenyon CJ, Thorsson L, Borgström L, et al. The effects of static charge in spacer devices on glucocorticosteroid aerosol deposition in asthmatic patients. Eur Respir J 1998; 11: 606–10

    PubMed  CAS  Google Scholar 

  22. Pierart F, Wildhaber JH, Vrancken I, et al. Washing plastic spacers in household detergent reduces electrostatic charge and greatly improves delivery. Eur Respir J 1999; 13: 673–8

    Article  PubMed  CAS  Google Scholar 

  23. Janssens HM, Devadason SG, Hop WC, et al. Variability of aerosol delivery via spacer devices in young asthmatic children in daily life. Eur Respir J 1999; 13: 787–91

    Article  PubMed  CAS  Google Scholar 

  24. Turpeinen M, Nikander K, Malmberg LP, et al. Metered dose inhaler add-on devices: is the inhaled mass of drug dependent on the size of the infant? J Aerosol Med 1999; 12: 171–6

    Article  PubMed  CAS  Google Scholar 

  25. Thorsson L, Edsbacker S. Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. Eur Resp J 1998; 12: 1340–5

    Article  CAS  Google Scholar 

  26. Onhoj J, Thorsson L, Bisgaard H. Lung deposition of inhaled drugs increases with age. Am J Respir Crit Care Med 2000; 162: 1819–22

    PubMed  CAS  Google Scholar 

  27. Janssens HM, Heijnen EM, de Jong VM, et al. Aerosol delivery from spacers in wheezy infants: a daily life study. Eur Respir J 2000; 16: 850–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

A study grant was given by Asche Chiesi GmbH, Hamburg, Germany.

The authors wish to thank Dr Frank Erdnüss for his help in preparing this manuscript.

No sources of funding were used to assist in the preparation of this article, and the authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Pediatric Pneumology and Allergology, Childrens Hospital, University Mainz, Langenbeckstrasse 1, D-55101, Mainz, Germany

    Wolfgang Kamin

  2. Inamed Research GmbH & Co. KG, Gauting, Germany

    Hilke Ehlich

Authors
  1. Wolfgang Kamin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hilke Ehlich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfgang Kamin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamin, W., Ehlich, H. In Vitro Comparison of Output and Particle Size Distribution of Budesonide from Metered-Dose Inhaler with Three Spacer Devices during Pediatric Tidal Breathing. Treat Respir Med 5, 503–508 (2006). https://doi.org/10.2165/00151829-200605060-00013

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00151829-200605060-00013

Keywords

Search

Navigation