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Pharmaceutical Research

, Volume 23, Issue 7, pp 1591–1596 | Cite as

Spray Pattern Analysis for Metered Dose Inhalers: Effect of Actuator Design

  • Hugh Smyth
  • Geoff Brace
  • Tony Barbour
  • Jim Gallion
  • Joe Grove
  • Anthony J. Hickey
Research Paper

Purpose

This study was conducted to identify the device factors influencing spray pattern and particle size to gain a more complete understanding of spray plume measurements.

Methods

A statistically designed experiment was used to investigate the influence of three actuator features (orifice diameter, expansion chamber depth, and orifice length) on spray pattern and particle size profiles. Custom-built actuators were manufactured and analyzed with laser light sheet illumination methods for spray patterns and laser diffraction for particle size analysis.

Results

In addition to orifice size, spray patterns were significantly influenced by the actuator orifice length and sump depth. Particle size analysis of the plumes generated from actuators used in these studies showed that all actuator features (orifice size, length, and sump depth) were significant factors influencing particle size.

Conclusions

The performance of propellant-based metered dose inhaler aerosols seems to be significantly related to sump depth and orifice length, in addition to orifice size. Rational design of propellant-based metered dose inhalers should therefore consider these variables in addition to formulation strategies and simply modifying orifice diameter.

Key words

aerosol plume actuator laser diffraction pMDIs spray pattern 

Notes

Acknowledgments

The authors would like to thank Bespak Inc., Apex, North Carolina, for financial support for this work. In addition, we would like to thank Helen Newell for providing advice in the preparation of the manuscript.

References

  1. 1.
    FDA, Guidance for industry metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products, CDERGUID|2180dft.wpd, Nov 1998, http://www.fda.gov/cder/guidance/2180dft.pdf. 1998.Google Scholar
  2. 2.
    ITFG/IPAC-RS Collaboration, C.T.a.M.T.T. Recommendations for tests and methods. A response to the FDA draft guidance for industry. 2001 [cited; Available from: http://www.ipacrs.com/PDFs/Recommendations_for.PDF.Google Scholar
  3. 3.
    Lefebvre, A. H 1989Atomization and spraysChigier, N. eds. Combustion: An International SeriesTaylor and FrancisNew YorkGoogle Scholar
  4. 4.
    H. D. C. Smyth et al. Spray pattern analysis for metered dose inhalers I: orifice size, particle size, and droplet motion correlations. Drug Dev. Ind. Pharm., in press.Google Scholar
  5. 5.
    Smyth, H. D. C., Hickey, A. J. 2003Multimodal particle size distributions emitted from HFA 134a solution pressurized metered dose inhalersAAPS PharmSciTech438CrossRefGoogle Scholar
  6. 6.
    Ganderton, D.,  et al. 2003The formulation and evaluation of a CFC-free budesonide pressurised metered dose inhalerRespir. Med.97S4S9PubMedCrossRefGoogle Scholar
  7. 7.
    Berry, J.,  et al. 2003Influence of the metering chamber volume and actuator design on the aerodynamic particle size of a metered dose inhalerDrug Dev. Ind. Pharm.29865876PubMedCrossRefGoogle Scholar
  8. 8.
    Ganderton, D.,  et al. 2002Modulite: a means of designing the aerosols generated by pressurized metered dose inhalersRespir. Med.96S3S8PubMedCrossRefGoogle Scholar
  9. 9.
    Ashworth, H. L.,  et al. 1991Delivery of propellant soluble drug from a metered dose inhalerThorax46245247PubMedCrossRefGoogle Scholar
  10. 10.
    Brambilla, G.,  et al. 1999Modulation of aerosol clouds produced by pressurized inhalation aerosolsInt. J. Pharm.1865361PubMedCrossRefGoogle Scholar
  11. 11.
    Clark, A. R. 1992Physics of aerosol formation by MDIs—limitations of the current approachJ. Biopharm. Sci.36976Google Scholar
  12. 12.
    D. Lewis et al. Effects of actuator orifice diameter on beclomethasone dipropionate delivery from a pMDI HFA solution formulation, in RDD VI. 1:363–364 (1998).Google Scholar
  13. 13.
    Polli, G. P.,  et al. 1969Influence of formulation on aerosol particle sizeJ. Pharm. Sci.58484486AprPubMedGoogle Scholar
  14. 14.
    J. A. Ranucci, D. Cooper, and K. Sethachutkul. Effect of actuator design on metered-dose inhaler plume-particle size. Pharm. Technol. 16:84, 86, 88, 90–92 (1992).Google Scholar
  15. 15.
    Smyth, H. D. C. 2003The influence of formulation variables on the performance of alternative propellant-driven metered dose inhalersAdv. Drug Deliv. Rev.55807828PubMedCrossRefGoogle Scholar
  16. 16.
    Dunbar, C. A., Watkins, A. P., Miller, J. F. 1997An experimental investigation of the spray issued from a pMDI using laser diagnostic techniquesJ. Aerosol Med.10351368PubMedGoogle Scholar
  17. 17.
    Clark, A. R. 1991Metered Atomization for Respiratory Drug DeliveryLoughborough University of TechnologyUKGoogle Scholar
  18. 18.
    Clark, A. R. 1996MDIs: physics of aerosol formationJ. Aerosol Med.9S19S26PubMedCrossRefGoogle Scholar
  19. 19.
    Dunbar, C. A. 1998Atomization mechanisms of the pressurized metered dose inhalerPart. Sci. Technol.15253271Google Scholar
  20. 20.
    Dunbar, C. A., Watkins, A. P., Miller, J. F. 1997Application of laser diagnostic techniques to characterize the spray issued from a pMDIProc. Int. Conf. Liq. At. Spray Syst.1641648Google Scholar
  21. 21.
    Dunbar, C. A., Watkins, A. P., Miller, J. F. 1997Characterization of the pMDI spray using numerical methodsProc. Int. Conf. Liq. At. Spray Syst.2876883Google Scholar
  22. 22.
    Dunbar, C. A., Watkins, A. P., Miller, J. F. 1997Theoretical investigation of the spray from a pressurized metered-dose inhalerAt. Sprays7417436Google Scholar
  23. 23.
    Finlay, W. H. 2001The Mechanics of Inhaled Pharmaceutical AerosolsAcademic PressLondonGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Hugh Smyth
    • 1
  • Geoff Brace
    • 2
    • 6
  • Tony Barbour
    • 6
  • Jim Gallion
    • 3
    • 6
  • Joe Grove
    • 4
    • 6
  • Anthony J. Hickey
    • 5
  1. 1.College of PharmacyUniversity of New MexicoAlbuquerqueUSA
  2. 2.Straightforward Solutions, LLCRaleighUSA
  3. 3.Tyco HealthcareRaleighUSA
  4. 4.AXON CorporationRaleighUSA
  5. 5.School of PharmacyUniversity of North CarolinaChapel HillUSA
  6. 6.Bespak Inc.ApexUSA

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