Advertisement

The AAPS Journal

, Volume 15, Issue 2, pp 511–522 | Cite as

Effect of Device Design on the Aerosolization of a Carrier-Based Dry Powder Inhaler—a Case Study on Aerolizer® Foradile®

  • Qi Tony Zhou
  • Zhenbo Tong
  • Patricia Tang
  • Mauro Citterio
  • Runyu Yang
  • Hak-Kim Chan
Research Article

Abstract

The objective of this study is to investigate the effect of device design of the Aerolizer® on the aerosolization of a carrier-based dry powder inhaler formulation (Foradile®). The Aerolizer was modified by reducing the air inlet size and mouthpiece length to 1/3 of the original dimensions, or by increasing the grid voidage. Aerosolization of the powder formulation was assessed on a multi-stage liquid impinger at air flow rates of 30, 60, and 100 L/min. Coupled CFD-DEM simulations were performed to investigate the air flow pattern and particle impaction. There was no significant difference in the aerosolization behavior between the original and 1/3 mouthpiece length devices. Significant increases in FPF total and FPF emitted were demonstrated when the inlet size was reduced, and the results were explained by the increases in air velocity and turbulence from the CFD analysis. No significant differences were shown in FPF total and FPF emitted when the grid voidage was increased, but more drugs were found to deposit in induction port and to a lesser extent, the mouthpiece. This was supported by the CFD-DEM analysis which showed the particle–device collisions mainly occurred in the inhaler chamber, and the cross-grid design increased the particle–device collisions on both mouthpiece and induction port. The air inlet size and grid structure of the Aerolizer® were found to impact significantly on the aerosolization of the carrier-based powder.

Key words

aerosolization computational fluid dynamics device design discrete element method dry powder inhalers 

Notes

ACKNOWLEDGMENTS

The authors acknowledge the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Australian Centre for Microscopy and Microanalysis, The University of Sydney. The study was financially supported by the Australian Research Council (grant DP110105161). Qi (Tony) Zhou is an Australian National Health and Medical Research Council (NHMRC) Early Career Fellow.

REFERENCES

  1. 1.
    Chan HK. Dry powder aerosol delivery systems: current and future research directions. J Aerosol Med Depos Clearance Eff Lung. 2006;19(1):21–7.CrossRefGoogle Scholar
  2. 2.
    Zhou Q, Morton DAV. Drug–lactose binding aspects in adhesive mixtures: controlling performance in dry powder inhaler formulations by altering lactose carrier surfaces. Adv Drug Deliv Rev. 2012;64(3):275–84.PubMedCrossRefGoogle Scholar
  3. 3.
    De Boer AH, Chan HK, Price R. A critical view on lactose-based drug formulation and device studies for dry powder inhalation: which are relevant and what interactions to expect? Adv Drug Deliv Rev. 2012;64(3):257–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Voss A, Finlay WH. Deagglomeration of dry powder pharmaceutical aerosols. Int J Pharm. 2002;248(1–2):39–50.PubMedCrossRefGoogle Scholar
  5. 5.
    Coates MS, Fletcher DF, Chan HK, Raper JA. Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 1: grid structure and mouthpiece length. J Pharm Sci. 2004;93(11):2863–76.PubMedCrossRefGoogle Scholar
  6. 6.
    Coates MS, Chan HK, Fletcher DF, Raper JA. Effect of design on the performance of a dry powder inhaler using computational fluid dynamics. Part 2: air inlet size. J Pharm Sci. 2006;95(6):1382–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Coates MS, Chan HK, Fletcher DF, Chiou H. Influence of mouthpiece geometry on the aerosol delivery performance of a dry powder inhaler. Pharm Res. 2007;24(8):1450–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Donovan MJ, Kim SH, Raman V, Smyth HD. Dry powder inhaler device influence on carrier particle performance. J Pharm Sci. 2012;101(3):1097–107.PubMedCrossRefGoogle Scholar
  9. 9.
    Shur J, Lee S, Adams W, Lionberger R, Tibbatts J, Price R. Effect of device design on the in vitro performance and comparability for capsule-based dry powder inhalers. AAPS J. 2012;14(4):667–676.Google Scholar
  10. 10.
    Tong ZB, Zheng B, Yang RY, Yu AB, Chan HK (2012). CFD-DEM investigation of the dispersion mechanisms in commercial dry powder inhalers. Powder Technol. 2012. doi: 10.1016/j.powtec.2012.07.012.
  11. 11.
    Young PM, Roberts D, Chiou H, Rae W, Chan HK, Traini D. Composite carriers improve the aerosolisation efficiency of drugs for respiratory delivery. J Aerosol Sci. 2008;39(1):82–93.CrossRefGoogle Scholar
  12. 12.
    Asking L, Olsson B. Calibration at different flow rates of a multistage liquid impinger. Aerosol Sci Technol. 1997;27(1):39–49.CrossRefGoogle Scholar
  13. 13.
    Chew NYK, Chan HK. In vitro aerosol performance and dose uniformity between the Foradile (R) Aerolizer (R) and the Oxis (R) Turbuhaler (R). J Aerosol Med Depos Clearance Eff Lung. 2001;14(4):495–501.CrossRefGoogle Scholar
  14. 14.
    Kumon M, Kwok PCL, Adi H, Heng D, Chan HK. Can low-dose combination products for inhalation be formulated in single crystalline particles? Eur J Pharm Sci. 2010;40(1):16–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhu HP, Zhou ZY, Yang RY, Yu AB. Discrete particle simulation of particulate systems: theoretical developments. Chem Eng Sci. 2007;62(13):3378–96.CrossRefGoogle Scholar
  16. 16.
    Wang B, Xu DL, Chu KW, Yu AB. Numerical study of gas–solid flow in a cyclone separator. Appl Math Model. 2006;30(11):1326–42.CrossRefGoogle Scholar
  17. 17.
    Launder BE, Reece GJ, Rodi W. Progress in development of a Reynolds-stress turbulence closure. J Fluid Mech. 1975;68:537–66.CrossRefGoogle Scholar
  18. 18.
    Chu KW, Wang B, Yu AB, Vince A. CFD-DEM modelling of multiphase flow in dense medium cyclones. Powder Technol. 2009;193(3):235–47.CrossRefGoogle Scholar
  19. 19.
    Coates MS, Chan HK, Fletcher DF, Raper JA. Influence of air flow on the performance of a dry powder inhaler using computational and experimental analyses. Pharm Res. 2005;22(9):1445–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Clark AR, Hollingworth AM. The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers—implications for In vitro testing. J Aerosol Med Depos Clearance Eff Lung. 1993;6(2):99–110.CrossRefGoogle Scholar
  21. 21.
    Srichana T, Martin GP, Marriott C. Dry powder inhalers: the influence of device resistance and powder formulation on drug and lactose deposition in vitro. Eur J Pharm Sci. 1998;7(1):73–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Zhou QT, Armstrong B, Larson I, Stewart PJ, Morton DAV. Understanding the influence of powder flowability, fluidization and de-agglomeration characteristics on the aerosolization of pharmaceutical model powders. Eur J Pharm Sci. 2010;40(5):412–21.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Qi Tony Zhou
    • 1
  • Zhenbo Tong
    • 2
  • Patricia Tang
    • 1
  • Mauro Citterio
    • 3
  • Runyu Yang
    • 2
  • Hak-Kim Chan
    • 1
  1. 1.Advanced Drug Delivery Group, Faculty of PharmacyThe University of SydneySydneyAustralia
  2. 2.School of Materials Science and EngineeringUniversity of New South WalesSydneyAustralia
  3. 3.R&D and Industrialization, Plastiape S.p.A.OsnagoItaly

Personalised recommendations