Pharmaceutical Research

, Volume 31, Issue 11, pp 2963–2974 | Cite as

A Novel High-Speed Imaging Technique to Predict the Macroscopic Spray Characteristics of Solution Based Pressurised Metered Dose Inhalers

  • Nicolas A. Buchmann
  • Daniel J. Duke
  • Sayed A. Shakiba
  • Daniel M. Mitchell
  • Peter J. Stewart
  • Daniela Traini
  • Paul M. Young
  • David A. Lewis
  • Julio Soria
  • Damon Honnery
Research Paper

ABSTRACT

Purpose

Non-volatile agents such as glycerol are being introduced into solution-based pMDI formulations in order to control mean precipitant droplet size. To assess their biopharmaceutical efficacy, both microscopic and macroscopic characteristics of the plume must be known, including the effects of external factors such as the flow generated by the patient’s inhalation. We test the hypothesis that the macroscopic properties (e.g. spray geometry) of a pMDI spray can be predicted using a self-similarity model, avoiding the need for repeated testing.

Methods

Glycerol-containing and glycerol-free pMDI formulations with matched mass median aerodynamic diameters are investigated. High-speed schlieren imaging is used to extract time-resolved velocity, penetration and spreading angle measurements of the pMDI spray plume. The experimental data are used to validate the analytical model.

Results

The pMDI spray develops in a manner characteristic of a fully-developed steady turbulent jet, supporting the hypothesis. Equivalent glycerol-containing and non glycerol-containing formulations exhibit similar non-dimensional growth rates and follow a self-similar scaling behaviour over a range of physiologically relevant co-flow rates.

Conclusions

Using the proposed model, the mean leading edge penetration, velocity and spreading rate of a pMDI spray may be estimated a priori for any co-flow conditions. The effects of different formulations are captured in two scaling constants. This allows formulators to predict the effects of variation between pMDIs without the need for repeated testing. Ultimately, this approach will allow pharmaceutical scientists to rapidly test a number of variables during pMDI development.

KEY WORDS

co-flow glycerol HFA high-speed schlieren imaging modelling pMDI 

ABBREVIATIONS

ACI

Andersen Cascade Impactor

BDP

Beclomethasone dipropionate

FPD

Fine particle dose

HFA

Hydrofluoroalkane

MMAD

Mass median aerodynamic diameter

pMDI

Pressurised Metered Dose Inhaler

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to acknowledge the financial support of the Australian Research Council (grant number DP120103510).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Nicolas A. Buchmann
    • 1
    • 6
  • Daniel J. Duke
    • 1
  • Sayed A. Shakiba
    • 1
  • Daniel M. Mitchell
    • 1
  • Peter J. Stewart
    • 2
  • Daniela Traini
    • 3
    • 4
  • Paul M. Young
    • 3
    • 4
  • David A. Lewis
    • 5
  • Julio Soria
    • 1
    • 7
  • Damon Honnery
    • 1
  1. 1.Department of Mechanical and Aerospace EngineeringMonash UniversityMelbourneAustralia
  2. 2.Faculty of Pharmacy and Pharmaceutical SciencesMonash UniversityMelbourneAustralia
  3. 3.Respiratory Technology, Woolcock Insititute of Medical ResearchUniversity of SydneySydneyAustralia
  4. 4.Discipline of Pharmacology, School of MedicineThe University of SydneySydneyAustralia
  5. 5.Chiesi LimitedChippenhamUK
  6. 6.Institute of Fluid Dynamics and AerodynamicsUniversität der Bundeswehr MünchenNeubibergGermany
  7. 7.Department of Aeronautical EngineeringKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia

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