Upload
others
View
4
Download
0
Embed Size (px)
Citation preview
Modeling Deposition in the Respiratory Tract: What Can We Learn That Impactors Don’t Tell Us
http://www.copleyscientific.com/images/ww/side/_resized/Pic-9_288_0_0_0_362_223.jpg http://www.labautomate.net/images/next-generation-impactor.jpg http://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0118454.g001 https://image.issuu.com/161128184357-57dbb0207b084e3f1d118b2742dbe378/jpg/page_1.jpg https://www.omicsonline.org/articles-images/pulmonary-respiratory-medicine-larger-bore-prong-6-376-g002.png
vs.
Computational Fluid Dynamics
https://en.wikipedia.org/wiki/Computational_fluid_dynamics https://commons.wikimedia.org/wiki/File:CFD_Shuttle.jpg http://mdx.plm.automation.siemens.com/marine http://fluidsengineering.asmedigitalcollection.asme.org/data/journals/jfega4/930613/fe_136_10_101101_f015.png
“Computational fluid dynamics (CFD) is a branch of fluid mechanics that uses numerical analysis and data structures to solve and analyze problems that involve fluid flows. Computers are used to perform the calculations required to simulate the interaction of liquids and gases with surfaces defined by boundary conditions.”
Comparison of Monodisperse Particle Deposition in the Pulmonary System: Experimental vs. CFD
Stahlhofen W, Rudolf G, James AC. J Aerosol Med 2, 285-308, 1989 Tian G, Hindle M, Lee S, Longest PW. Pharm Res 32, 3170-3187, 2015
Comparison of CFD Predicted Deposition Patterns and Deposition Measured via Imaging
Novolizer DPI Respimat Soft Mist Inhaler
MP = mouthpiece C= central pulmonary compartment MT = mouth + trachea I = intermediate pulmonary compartment P = peripheral pulmonary compartment
Tian G, Hindle M, Lee S, Longest PW. Pharm Res 32, 3170-3187, 2015; Newman Respir J 16, 178-183, 2000; Newman Chest 113, 957-963, 1998
What About Deposition in the Upper Respiratory Tract?
Ghahramani E, Abouali O, Emdad H, Ahmadi G. J Aerosol Sci 67, 188-206, 2014.
The Challenge of CFD Model Development Specifying the Mesh
Engelhardt L, Rohm M, Mavoungou C, Schindowski K, Schafmeister A, Simon U. Pharm Res 33, 1337-1350. 2016.
Modeling Airflow Velocities in the Nasal Cavity
Model Measured
Engelhardt L, Rohm M, Mavoungou C, Schindowski K, Schafmeister A, Simon U. Pharm Res 33, 1337-1350. 2016
What Do Typical Nasal Deposition Patterns Look Like?
Foo, MY., PhD Thesis, University of Iowa 2007
De
po
sit
ion
Fra
cti
on
What Do CFD Nasal Models Predict?
Dastan A, Abouali O, Ahmadi G. J Aerosol Sci 69, 132-149, 2014
CFD Predictions of Deposition Patterns
Ghahramani E, Abouali O, Emdad H, Ahmadi G. J Aerosol Sci 67, 188-206, 2014
Linking CFD and PK Models
Rygg A, Hindle M, Longest PW J Pharm Sci 105, 1995-2004, 2016
But Noses Come in All Shapes and Sizes….
Zhu J, Lee H, Lim K, Lee S, Wang, D Respiratory Physiology & Neurobiology 175, 62-69, 2011
But Noses Come in All Shapes and Sizes….
Engelhardt L, Rohm M, Mavoungou C, Schindowski K, Schafmeister A, Simon U. Pharm Res 33, 1337-1350, 2016
But Noses Come in All Shapes and Sizes….
• “Current Study” 9 Taiwanese adults
• Particle loss protocol ∆ particles inspired-expired • Taiwanese showed lower
particle deposition efficiency than Caucasians
But Noses Come in All Shapes and Sizes….
Carrigy NB, Rzycki CA, Golshahi L, Finlay WH J Aerosol Med 27, 149-169, 2014
But Noses Come in All Shapes and Sizes….
Conclusions and Recommendations • Computational fluid dynamic models are powerful tools to address
questions regarding particle deposition and spray performance in the respiratory tract.
• Good correlation between CFD and experimental respiratory deposition patterns have been observed.
• While the exact anatomical measurements of the respiratory tract will vary, similar deposition patterns are observed.
• CFD modeling will improve the opportunity to evaluate population-based differences (age, race, disease state) in respiratory delivery system efficacy without the need to conduct human trials.
• Be cautious in data interpretation – models will show differences! It is important to understand when those differences are clinically relevant or able to demonstrate product quality and when they do not!
Acknowledgements
Arthur Foo (University of Iowa, Novartis Pharmaceuticals) Yung-Sung Cheng (Lovelace Respiratory Research Institute) Wei-Chung Su (Lovelace Respiratory Research Institute) Namita Sawant (University of Iowa) The pediatric nasal deposition studies were funded by FDA U01 5U01FD004275 "The Critical Path Manufacturing Sector Research Initiative” to NIPTE.