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Inhaler Spray Investigation Using High-Speed Phase-Contrast X-Ray and Schlieren Imaging

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Abstract

Purpose

The first pressurised metered dose inhaler (pMDI) was introduced in 1956. Even with excellent inhaler technique typically only 20% of the dose deposits in the lungs where needed. It is hoped that a better understanding of the initial plume formation and expansion during dose release can help improve modelling, devices and ultimately transport to the lungs. We have used two high-speed imaging techniques to investigate the transient dose event.

Methods

Synchrotron phase-contrast X-Ray imaging is a technique that is sensitive to variations in the refractive index of materials in the X-ray region. Similarly, Schlieren imaging is an optical technique sensitive to the refractive index gradients which are often present in pMDI plumes due to gas density variations. We have combined and synchronised both techniques to investigate three commercial pMDIs actuators during dose release for various actuator/formulation combinations.

Results

We have observed temporal phases of propellant flowing in the orifice channel. At early times flash boiling takes place and drives gas emission, steep plume density gradients and liquid jets/droplets at the orifice. Evaporating liquid is present in the sump long after the dose is finished. Regional counter-flow is seen in plumes emitted into a mouth-throat geometry.

Conclusions

As the foamy liquid-vapour mixture is forced out of the sump and into the orifice the liquid walls of the bubbles break into fragments which are forced out of the sump and tend to form a liquid-gas flow in the orifice channel. The period of high density plume observed by the schlieren technique corresponds to flash-boiling-driven liquid exiting the orifice channel.

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Abbreviations

API:

Active pharmaceutical ingredient

APSD:

Aerosol particle size distribution

CFD:

Computational fluid dynamics

DPI:

Dry powder inhaler

k:

Gladstone-Dale coefficient

n:

Refractive index

pMDI:

Pressurised metered dose inhaler

ρ:

Gas density

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Acknowledgments and Disclosures

We acknowledge the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities and we thank Alexander Rack, Margie Olbinado and colleagues for assistance in using beam line ID19. We also acknowledge the engineering and tool-making staff of Prior PLM Medical for the design and manufacture of the Schlieren setup and experimental fixture.

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Authors and Affiliations

  1. Prior PLM Medical, IDA Business & Technology Park, Carrick-on-Shannon, N41 WK46, Ireland

    Alan Patrick McKiernan

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  1. Alan Patrick McKiernan
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Correspondence to Alan Patrick McKiernan.

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McKiernan, A.P. Inhaler Spray Investigation Using High-Speed Phase-Contrast X-Ray and Schlieren Imaging. Pharm Res 36, 120 (2019). https://doi.org/10.1007/s11095-019-2657-9

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  • DOI: https://doi.org/10.1007/s11095-019-2657-9

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