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Particle Aerosolisation and Break-up in Dry Powder Inhalers 1: Evaluation and Modelling of Venturi Effects for Agglomerated Systems

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ABSTRACT

Purpose

This study utilized a combination of computational fluid dynamics (CFD) and standardized entrainment tubes to investigate the influence of turbulence on the break-up and aerosol performance of a model inhalation formulation.

Methods

Agglomerates (642.8 μm mean diameter) containing 3.91 μm median diameter primary spherical mannitol particles were prepared by spheronisation. A series of entrainment tubes with different Venturi sections were constructed in silico, and the flow pattern and turbulence/impaction parameters were predicted using CFD. The entrainment models were constructed from the in silico model using three-dimensional printing. The aerosol performance of the mannitol was assessed by entraining the agglomerates into the experimental tubes at a series of flow rates and assessing the size distribution downstream of the venturi via in-line laser diffraction.

Results

A series of parameters (including Reynolds number (Re), turbulence kinetic energy, turbulence eddy frequency, turbulence length-scale, velocity and pressure drop) were calculated from the CFD simulation. The venturi diameter and volumetric flow rate were varied systematically. The particle size data of the agglomerated powders were then correlated with the CFD measurements. No correlation between turbulence and aerosol performance could be made (i.e. at a Reynolds number of 8,570, the d0.1 was 52.5 μm ± 19.7 μm, yet at a Reynolds number of 12,000, the d0.1 was 429.1 μm ± 14.8 μm). Lagrangian particle tracking indicated an increase in the number of impactions and the normal velocity component at the wall, with increased volumetric airflow and reduced venturi diameter. Chemical analysis of the mannitol deposited on the walls showed a linear relationship with respect to the theoretical number of impactions (R2 = 0.9620). Analysis of the relationship between the CFD results and the experimental size data indicated a critical impact velocity was required to initiate agglomerate break-up (∼0.4 m.s−1).

Conclusion

While this study focussed on the effect of turbulence on agglomerate break-up, the small amount of impaction, which inevitably occurs in the venturi assembly, appeared to dominate agglomerate break-up in this dry powder system.

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ACKNOWLEDGEMENTS

This research was supported under the Australian Research Council’s Linkage Projects funding scheme (project LP0776892). The views expressed herein are those of the authors and are not necessarily those of the Australian Research Council.

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Authors and Affiliations

  1. Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia

    William Wong, Daniela Traini, Hak-Kim Chan & Paul M. Young

  2. School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, NSW, 2006, Australia

    David F. Fletcher

  3. Pharmaxis Ltd., Unit 2, 10 Rodborough Rd, Frenchs Forest, Sydney, NSW, 2086, Australia

    John Crapper

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  1. William Wong
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  2. David F. Fletcher
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  3. Daniela Traini
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  4. Hak-Kim Chan
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  5. John Crapper
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  6. Paul M. Young
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Correspondence to Paul M. Young.

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Wong, W., Fletcher, D.F., Traini, D. et al. Particle Aerosolisation and Break-up in Dry Powder Inhalers 1: Evaluation and Modelling of Venturi Effects for Agglomerated Systems. Pharm Res 27, 1367–1376 (2010). https://doi.org/10.1007/s11095-010-0128-4

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  • DOI: https://doi.org/10.1007/s11095-010-0128-4

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