An in vitro analysis of the output of budesonide from different nebulizers,☆☆,

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Abstract

Background: Inhaled corticosteroids are increasingly used in the treatment of asthma, and many different nebulizers are available to aerosolize steroid medications. There are few comparative data on their ability to do so. Objective: Our purpose was to determine the particle size and mass output of budesonide nebulizer suspension from different nebulizers. Methods: In vitro measurement of drug particle size and total drug output from 3 nebulizers (the Pari LC Plus, the Pari LC Star, and the Medicaid Ventstream) was performed under simulated breathing conditions. Nebulizers were charged with 2 mL (500 μg) of budesonide suspension. A sinus pump was used to draw aerosol from the nebulizers onto a filter during simulated inspiration at tidal volumes of 150 and 600 mL, mimicking pediatric and adult use. Aerosol particle size was determined separately by inertial impaction. Results: The LC Plus nebulizer had the highest initial output rate and delivered the most budesonide at both breathing patterns. The maximal output rates of the Ventstream and LC Star nebulizers was half that of the LC Plus, but the LC Star nebulizer continued nebulization for longer and delivered twice as much budesonide as the Ventstream did. However, the Ventstream produced the smallest particles, mass median diameter 3.1 μm compared with 3.8 μm for the LC Star and 4.1 μm for the LC Plus. Conclusions: This study has identified differences among the nebulizers that would not have been apparent with current standards for nebulizer assessment. Incorporation of breathing simulation in the study imitates patient use and allows effective nebulization times to be predicted. The results suggest that the nebulizers studied would deliver different masses of budesonide to the lungs and to the upper airway. This may have important consequences in determining the efficacy and side effect profile of budesonide. (J Allergy Clin Immunol 1999;104:1168-73.)

Section snippets

Nebulizers and medication

Three jet nebulizer-compressor combinations were assessed: the LC Plus nebulizer and Turboboy compressor (38G00, operating pressure 0.7 bar, driving gas flow 5 L/min (Pari GmbH, Starnberg, Germany), the LC Star nebulizer and Turboboy compressor (38G00, Pari GmbH), and the Ventstream nebulizer and Portaneb compressor (operating pressure 0.95 bar, driving gas flow 6 L/min, Medicaid, Pagham, UK) were assessed with budesonide nebulizer suspension (500 μg in 2 mL, Pulmicort, Astra, Kings Langley,

Particle size

For the nebulizers assessed with the MSLI, the MMAD, the GSD, the mass of drug, and the percentage nebulizer output collected on stage 4 and the filter of the MSLI, representing drug particles smaller than 6.1 μg, are given in Table I.

. Mean and (95% confidence intervals)

Empty CellMMAD (μm)GSDDrug <6.1 μm (μq)Percent <6.1 μm
LC Plus/Turboboy4.1 (3.9-4.2)2.1 (2.0-2.2)95.0 (87.0-103.1)69.8 (67.6-72.0)
LC Star/Turboboy3.8 (3.5-4.0)1.9 (1.8-1.9)118.1 (113.1-123.1)77.2 (71.3-83.1)
Ventstream/Portaneb3.1 (2.8-3.3)

DISCUSSION

This in vitro study has detected large differences in the delivery of a corticosteroid drug from different nebulizers. Patients using one nebulizer may receive more than twice as much drug from it compared with another. This may be crucial in the delivery of corticosteroids, where dose-dependent effects may occur.11 It is also important to define the dose of medication administered in drug trials and dose equivalence studies. Therapeutic failure may occur in such trials, or the wrong

Acknowledgements

We thank Judith Jackson for technical support.

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    Supported by a grant from Pari GmbH.

    ☆☆

    Reprint requests: Peter W. Barry, MRCPI, Department of Child Health, University of Leicester, Clinical Sciences Building, Leicester Royal Infirmary, PO Box 65, Leicester, LE2 7LX United Kingdom.

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