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16 April 2020 Inhalation Pharmaceutical Research, 33(5), 1249-1258. http:// doi.org/10.1007/s11095-016-1869-5. 8. Duke, D. J., Scott, H. N., Kusangaya, A. J., Kasten- gren, A. L., Matusik, K., Young, P., et al. (2019). Drug Distribution Transients in Solution and Suspen- sion-Based Pressurised Metered Dose Inhaler Sprays. International Journal of Pharmaceutics, 566, 463-475. http://doi.org/10.1016/j.ijpharm.2019.05.067. 9. Duke, D. J., Kastengren, A. L., Mason-Smith, N., Chen, Y., Young, P. M., Traini, D., et al. (2015). Tempo- rally and Spatially Resolved X-ray Fluorescence Mea- surements of In-situ Drug Concentration in Metered- Dose Inhaler Sprays. Pharmaceutical Research, 33, 816- 825. http://doi.org/10.1007/s11095-015-1828-6. 10. Kastengren, A. L., Ilavsky, J., Viera, J. P., Payri, R., Duke, D. J., Swantek, A., et al. (2017). Measurements of Droplet Size in Shear-Driven Atomization Using Ultra-Small Angle X-ray Scattering. International Jour- nal of Multiphase Flow, 92, 131-139. http://doi. org/10.1016/j.ijmultiphaseflow.2017.03.005. 11. Ilavsky, J., Jemian, P. R., Allen, A. J., Zhang, F., Levine, L. E. and Long, G. G. (2009). Ultra-Small-An- gle X-ray Scattering at the Advanced Photon Source. Journal of Applied Crystallography, 42(3), 469-479. http://doi.org/10.1107/S0021889809008802. Acknowledgements e author acknowledges funding support from the Australian Research Council (DE170100018, LP160101845) and Chiesi Limited. Use of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science by Argonne National Labora- tory, is supported by the US DOE under Contract No. DE-AC02-06CH11357. This research/project was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Govern- ment. e author also wishes to acknowledge the many students, scientists and technicians who contributed to the research presented here. From Argonne National Laboratory: Dr. Alan Kastengren, Dr. Katarzyna Matusik, Dr. Brandon Sforzo, Dr. Jan Ilavsky, Dr. Mat- thew Frith, Dr. Kamel Fezzaa and Dr. Don Walko. From the Woolcock Institute of Medical Research, Aus- tralia: Prof. Paul Young, Prof. Daniela Traini and Dr. Yang Chen. From Monash University, Australia: Mr. Harry Scott, Mr. Anesu Kusangaya, Dr. Nicholas Mason-Smith, Dr. Daniel Edgington-Mitchell and Prof. Damon Honnery. Daniel J. Duke, PhD, is a Senior Lecturer in the Depart- ment of Mechanical & Aerospace Engineering, Monash University, Wellington Road, Clayton Victoria 3800 Aus- tralia, Tel.: +61 3 9905 6139, daniel.duke@monash.edu, http://daniel-duke.com. the research question being asked, one or more tech- niques would be used. Some techniques, such as radiog- raphy and fluorescence, necessarily go hand-in-hand. Others such as phase-contrast and USAXS can be per- formed, when necessary, to address specific questions. Research to date has been exclusively on pMDIs but these techniques may also be used in the future to evalu- ate other types of inhalers, such as DPIs or nebulizers. Synchrotron radiation offers a means for investigating the behavior of complex fluid mixtures inside small devices such as pMDIs. Synchrotron X-rays can pro- vide valuable quantitative information on drug distri- bution, spray density, and droplet and particle proper- ties; metrics difficult to obtain by other means. Syn- chrotron measurements also can provide direct evi- dence of the effects of changes to actuator design and formulation composition on the behavior of a device, a formulation or both. is can shorten the design feed- back loop and allow for more rapid development and assessment of prototype devices to facilitate the intro- duction of new inhaled pharmaceutical products. While synchrotron facilities are not widely available, it is hoped they will benefit the development of a wide range of inhaled pharmaceutical products. References 1. Versteeg, H. K. (2017). Using Phase Doppler Ane- mometry and High Speed Imaging to Analyze MDI Spray Plume Dynamics. Presented at Respiratory Drug Delivery Europe 2017, Nice, France. 2. Dong, Y-D. and Boyd, B.J. (2011). Applications of X-ray Scattering in Pharmaceutical Science. Interna- tional Journal of Pharmaceutics, 417, 101-111. http:// doi.org/10.1016/j.ijpharm.2011.01.022. 3. Als-Nielsen, J. and McMorrow, D. (2011). Ele- ments of Modern X-ray Physics (2nd ed.). Hoboken, NJ, US: John Wiley & Sons, Inc. http://doi. org/10.1002/9781119998365. 4. Kastengren, A. and Powell, C. F. (2014). Synchro- tron X-ray Techniques for Fluid Dynamics. Experi- ments in Fluids, 55(3), 1686. http://doi.org/10.1007/ s00348-014-1686-8. 5. McKiernan, A. P. (2019). Inhaler Spray Investigation Using High-Speed Phase-Contrast X-Ray and Schlie- ren Imaging, Pharmaceutical Research 36 120-132. http://doi.org/10.1007/s11095-019-2657-9. 6. Mason-Smith, N., Duke, D. J., Kastengren, A. L., Traini, D., Young, P. M., Chen, Y., et al. (2017). Revealing pMDI Spray Initial Conditions: Flashing, Atomisation and the Effect of Ethanol. Pharmaceuti- cal Research, 34, 718-729. http://doi.org/10.1007/ s11095-017-2098-2. 7. Mason-Smith, N., Duke, D. J., Kastengren, A. L., Stewart, P. J., Traini, D., Young, P. M., et al. (2016). Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography.