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Pharmaceutical Research

, Volume 23, Issue 8, pp 1765–1775 | Cite as

Applicability of an Ultrasonic Nebulization System for the Airways Delivery of Beclomethasone Dipropionate in a Murine Model of Asthma

  • Boška Hrvačić
  • Berislav Bošnjak
  • Marijan Tudja
  • Milan Mesić
  • Mladen Merćep
Research Paper

Purpose

We have assessed the use of an ultrasonic nebulization system (UNS), composed of ultrasonic nebulizer and diffusion dryer filled with charcoal, for the effective delivery of beclomethasone to the airways in a murine asthma model.

Methods

Solution of beclomethasone in ethanol was aerosolized using an ultrasonic nebulizer. Passage of the aerosol through a drying column containing charcoal and deionizer produced dry beclomethasone particles. Particles were delivered to BALB/c mice placed in a whole-body exposition chamber 1 h before intranasal challenge with ovalbumine. Efficacy of beclomethasone delivery was evaluated by examining bronchoalveolar lavage fluid (BALF) cytology.

Results

Effect of three UNS system parameters on aerosol particle size was investigated. The critical parameter affecting the size of dry particles was beclomethasone concentration in aerosolized solution and solution flow rate while power level of ultrasonic nebulizer generator had no effect. Administration of beclomethasone at calculated dose of 150 μg/kg to mice significantly decreased total cell number and relative eosinophil number in BALF.

Conclusions

The UNS system produces a monodisperse aerosol that can be used for inhalative delivery of poorly water soluble substances to experimental animals. The UNS system minimizes formulation requirements and allows rapid and relatively simple efficacy and toxicity testing in animals.

Key words

asthma beclomethasone dipropionate dry powder inhalation delivery mice ultrasonic nebulization system 

Abbreviations

BALF

bronchoalveolar lavage fluid

beclomethasone

beclomethasone dipropionate

COPD

chronic obstructive pulmonary disease

DPI

dry powder inhaler

FPF(<2.20 μm)

fine particle fraction <2.20 μm aerodynamic diameter

GSD

geometric standard deviation

pMDI

pressurized metered-dose inhaler

SD

standard deviation

UNS

ultrasonic nebulization system

Notes

Acknowledgments

This work was supported by PLIVA Research Institute, Inc. Authors wish to thank dr. Michael J. Parnham for critical reading of the manuscript. Authors also wish to thank Ms. Anica Pešut and Milka Horvatinčić and Mr. Željko Osman for their excellent technical assistance.

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Boška Hrvačić
    • 1
  • Berislav Bošnjak
    • 1
  • Marijan Tudja
    • 2
  • Milan Mesić
    • 1
  • Mladen Merćep
    • 1
  1. 1.PLIVA Research Institute Ltd.ZagrebCroatia
  2. 2.PLIVA Croatia Ltd.ZagrebCroatia

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