Pharmaceutical Research

, Volume 23, Issue 9, pp 2200–2209 | Cite as

Correlation between Inertial Impaction and Laser Diffraction Sizing Data for Aerosolized Carrier-based Dry Powder Formulations

  • Xian-Ming Zeng
  • Helen B. MacRitchie
  • Christopher Marriott
  • Gary P. Martin
Research Paper
First Online:
Received:
Accepted:

Abstract

Purpose

The purpose of the study was to determine whether the drug fine particle fraction (FPF) from different dry powder aerosol formulations measured by laser diffraction at a range of flow rates correlated with that measured by inertial impaction.

Materials and Methods

Ten binary formulations were prepared containing 1.5% w/w salbutamol base or sulphate, blended with the sieved (63–90 μm) fraction of different sugars (regular lactose, spray-dried lactose, sorbitol, dextrose or maltose). A further six ternary formulations were prepared containing 1.5% w/w salbutamol sulphate, 97% coarse lactose (63–90 μm) and 1.5% micronised or intermediate-sized lactose (1–50 μm). The FPF particles (< 5 μm) of these formulations were measured by laser diffraction and inertial impaction at flow rates between 28.3 and 100 l min−1.

Results

When only the particles with diameter < 60 μm obtained by laser diffraction were considered the FPF (< 5 μm) could be determined and this enabled the aerosolisation of all 16 blends to be feasibly compared at flow rates ranging from 28.3 to 100 l min−1. A significant linear correlation was found between the fine fractions measured by laser diffraction and the salbutamol fine fractions determined by inertial impaction (r 2 = 0.934). Such correlation was also confirmed for formulations containing added fine lactose.

Conclusion

Particle size measured by laser diffraction under the employed conditions reflected the aerodynamic properties of the drug. Laser diffraction can be used as on-, in- and/or at-line measurements and controls for dry powder aerosol formulations.

Key words

dry powder inhaler fine particle fraction formulations inertial impaction laser diffraction 
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References

  1. 1.
    M. J. Telko, and A. J. Hickey. Dry powder inhaler formulation. Respir. Care 50:1209–1227 (2005).PubMedGoogle Scholar
  2. 2.
    I. J. Smith, and M. Parry-Billings. The inhalers of the future? A review of dry powder devices on the market today. Pulm. Pharmacol. Ther. 16:79–95 (2003).PubMedCrossRefGoogle Scholar
  3. 3.
    G. Fradley and G. Mahon, Trends in device selection for inhalation markets. In Proc. drug delivery to the lungs 16, Edinburgh, 2005, pp. 38–41.Google Scholar
  4. 4.
    Nektar Press Release. Nektar Reports on Pfizer and Sanofi-Aventis Statement on Status of Exubera. http://www.nektar.com/content/pr_1130520573 (accessed 12/23/2005).
  5. 5.
    L Garcia-Contreras, and H. D. C. Smyth. Liquid-spray or dry-powder systems for inhaled delivery of peptide and proteins? Am J Drug Deliv. 3:29–45 (2005).CrossRefGoogle Scholar
  6. 6.
    J. P. Mitchell, and M. W. Nagel. Particle size analysis of aerosols from medicinal inhalers. KONA 22:32–65 (2004).Google Scholar
  7. 7.
    US Food and Drug Administration. Guidance for Industry PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. September 2004. http://www.fda.gov/cder/guidance/6419fnl.pdf (accessed 12/23/2005).
  8. 8.
    A. R. Clark. The use of laser diffraction for the evaluation of aerosol clouds generated by medical nebulisers. Int. J. Pharm. 115:69–78 (1995).CrossRefGoogle Scholar
  9. 9.
    F. Moren. Pressurized aerosols for inhalation. Int. J. Pharm. 8:1–10 (1981).CrossRefGoogle Scholar
  10. 10.
    B. Olsson, H. Jægfeldt, K. Hed, and H. Ludback. Correlation between laser scattering and inertial impaction for the particle distribution characterisation of Bricanyl turbohaler. J. Aerosol Sci. 19:1107–1111 (1988).Google Scholar
  11. 11.
    M. Everard, S. G. Devadason, V. B. Sunderland, and P. N. Le Souef. An alternative aerosol delivery system for amiloride. Thorax 50:517–519 (1995).PubMedCrossRefGoogle Scholar
  12. 12.
    J. Ziegler, and H. Wachtel. Comparison of cascade impaction and laser diffraction for particle size distribution measurements. J. Aerosol Med. 18:311–324 (2005).PubMedCrossRefGoogle Scholar
  13. 13.
    H. D. Smyth, and A. J. Hickey. Multimodal particle size distributions emitted from HFA-134a solution pressurized metered-dose inhalers. AAPS PharmSciTech. 4:38 (2003).PubMedCrossRefGoogle Scholar
  14. 14.
    X. M. Zeng, G. P. Martin, S.-K. Tee, A. A. Ghoush, and C. Marriott, Effects of particle size and adding sequence of fine lactose on the deposition of salbutamol sulphate from a dry powder formulation. Int. J. Pharm. 182:133–144 (1999).PubMedCrossRefGoogle Scholar
  15. 15.
    G. P. Martin, A. E. Bell, and C. Marriott. An in vitro method for assessing particle deposition from metered pressurised aerosols and dry powder inhalers. Int. J. Pharm. 44:57–63 (1988).CrossRefGoogle Scholar
  16. 16.
    B. G. Simonsson. Anatomical and pathophysiological considerations in aerosol therapy. Eur. J. Resp. Dis., Suppl. 119:7–14 (1982).Google Scholar
  17. 17.
    K. D. Horton, R. D. Miller, and J. P. Mitchell. Characterisation of a condensation-type monodisperse aerosol generator (MAGE). J. Aerosol Sci. 22:347–363 (1991).CrossRefGoogle Scholar
  18. 18.
    K. Willeke and P. A. Baron. In K. Willeke and P. A. Baron (eds.), Aerosol Measurement: Principles, Techniques and Applications, Van Nostrand Reinhold, New York, 1993.Google Scholar
  19. 19.
    H. C. Van de Hulst, Light Scattering by Small Particles. Dover, New York, 1981.Google Scholar
  20. 20.
    A. H. de Boer, D. Gjaltema, P. Hagedoorn, and H. W. Frijlink, Characterization of inhalation aerosols: a critical evaluation of cascade impactor and laser diffraction technique. Int. J. Pharm. 249:219–231 (2002).PubMedCrossRefGoogle Scholar
  21. 21.
    P. Kippax. Appraisal of the laser diffraction particle-sizing technique. Pharm. Technol pp. 88–96 (2005) March.Google Scholar
  22. 22.
    International Standards Organization. Particle Size Analysis_laser Diffraction Methods. Part 1. General Principles ISO Geneva, Switzerland, 13320–13321, 1999.Google Scholar
  23. 23.
    J. Swithenbank, J. M. Beer, D. S. Taylor, and G. C. MeCreath. A laser diagnostic technique for the measurement of droplet and particle size distribution. Prog Aeronaut. Sci. 53:421 (1977).Google Scholar
  24. 24.
    A. Annapraguda, and A. Adjei. An analysis of the Fraunhofer diffraction method for particle size distribution analysis and its application to aerosolized sprays. Int. J. Pharm. 127:219–227 (1996).CrossRefGoogle Scholar
  25. 25.
    A. H. de Boer, D. Gjaltema, P. Hagedoorn, M. Schaller, W. Witt, and H. W. Frijlink. Design and application of a new modular adapter for laser diffraction characterization of inhalation aerosols. Int. J. Pharm. 249:233–245 (2002).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Xian-Ming Zeng
    • 1
    • 2
  • Helen B. MacRitchie
    • 1
  • Christopher Marriott
    • 1
  • Gary P. Martin
    • 1
  1. 1.King's College LondonPharmaceutical Science Research DivisionLondonUK
  2. 2.Medway School of PharmacyUniversities of Kent and GreenwichChatham MaritimeUK

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