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

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 pMDI performance, it is necessary to evaluate pMDIs in vitro for delivered dose and particle size distributions under different conditions.

Methods: Fluticasone 125 mu g, budesonide 200 mu g, beclomethasone HFA100 mu g, and ciclesonide 160 mu g were compared for delivered dose and particle size using laser diffraction analysis with inspiratory flow rates of 10, 20 and 30 Us.

Results: The volume median diameter of budesonide wits 3.5 mu m, fluticasone 2.8 mu m, beclomethasone and ciclesonide both 1.9 mu m. 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 1.1-3.1 mu m. The changes in delivered dose during the Lifespan for the fluticasone 125 and 250 may have implications for patient care. (C) 2009 Elsevier Ltd. All rights reserved.