Comparative in vitro evaluation of four corticosteroid metered dose inhalers: Consistency of delivered dose and particle size distribution

de Vries, Tjalling W.; Rottier, Bart L.; Gjaltema, Doetie; Hagedoorn, Paul; Frijlink, Henderik W.; de Boer, Anne H.

doi:10.1016/j.rmed.2009.02.010

« Previous Next »Respiratory Medicine
Volume 103, Issue 8 , Pages 1167-1173, August 2009

Comparative in vitro evaluation of four corticosteroid metered dose inhalers: Consistency of delivered dose and particle size distribution

Tjalling W. de Vries
- Department of Paediatrics, Medical Centre Leeuwarden, P.O. Box 888, 8901 BR Leeuwarden, The Netherlands
- Corresponding author. Tel.: +31 58 2863385; fax: +31 58 2863390.
Bart L. Rottier
- Beatrix Children's Hospital, Division of Paediatric Pulmonology and Allergology, University Hospital Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
Doetie Gjaltema
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
Paul Hagedoorn
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
Henderik W. Frijlink
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
Anne H. de Boer
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands

Received 27 September 2008; accepted 14 February 2009. published online 09 March 2009.

Summary

Introduction

Recent developments concerning pressurized metered dose inhalers (pMDIs) with inhaled corticosteroids (ICS) are the introduction of ciclesonide and the replacement of propellants. As the results of in vivo studies depend on pMDIperformance, it is necessary to evaluate pMDIs in vitro for delivered dose and particle size distributions under different conditions.

Methods

Fluticasone 125μg, budesonide 200μg, beclomethasone HFA100μg, and ciclesonide 160μg were compared for delivered dose and particle size using laser diffraction analysis with inspiratory flow rates of 10, 20 and 30l/s.

Results

The volume median diameter of budesonide was 3.5μm, fluticasone 2.8μm, beclomethasone and ciclesonide both 1.9μm. The mouthpiece retention was up to 30% of the nominal dose for beclomethasone and ciclesonide, 11–19% for the other pMDIs. Lifespan, flow rate, and air humidity had no significant influence on particle size distribution. The delivered dose of beclomethasone, budesonide, and ciclesonide remained constant over the lifespan. The delivered dose of fluticasone 125 decreased from 106% to 63%; fluticasone 250 also decreased whereas fluticasone 50 remained constant.

Conclusions

There is a significant difference in median particle size distribution between the different ICS pMDIs. Air humidity and inspiratory flow rate have no significant influence on particle size distribution. Ciclesonide 160 and beclomethasone 100 deliver the largest fine particle fractions of 1.1–3.1μm. The changes in delivered dose during the lifespan for the fluticasone 125 and 250 may have implications for patient care.

Keywords: Inhaled corticosteroid, Pressurized metered dose inhaler, Particle size distribution, Laser diffraction, Delivered dose

Abbreviations: pMDI, pressurized metered dose inhaler, ICS, inhaled corticosteroid, PSD, particle size distribution, CFC, chlorofluorocarbon, HFA, hydrofluoroalkane, LDA, laser diffraction analysis, FP, fluticasoneproprionate, BUD, budesonide, BDP, beclomethasone dipropionate HFA, CIC, ciclesonide, FPF, fine particle fraction, MMAD, mass median aerodynamic diameter, VMD, volume median diameter