inhaler testing machine
TRANSCRIPT
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2004 Mechanical & Industrial Engineering, University of Toronto
A Device to Model a Human Lung to Determine the Delivery Efficiency of Inhaled
Pharmaceutical Aerosols
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Background Existing Models Developed Models
Flexible Lung ModelRigid Lung Model
Testing Methodology Model Assessment and Conclusion
2004 Mechanical & Industrial Engineering, University of Toronto
Overview
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Medications are administrated by: Oral ingestion
Intravenous Injections
Respiratory system (Pharmaceutical Inhalers)
2004 Mechanical & Industrial Engineering, University of Toronto
Medication Administration
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Pharmaceutical InhalersAdvantages Quick absorption into the blood stream
Less medicine for similar therapeutic result
Projection 50% of medication through inhalers
Problem Less than 20% of inhaled dosage reaches the lower respiratory system
Need More efficient pharmaceutical inhalers
Means of testing pharmaceutical inhalers
2004 Mechanical & Industrial Engineering, University of Toronto
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Inhalers
Breath Activated Inhaler
Nebulizer
Pressurized Metered
Dose Inhaler (pMDI)
Pressurized Aerosol
Inhaler with Spacer
Dry Powder Inhaler (DPI)
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ADVAIR pMDI 120 dose (125 mcg) Treats the two main components of asthma, airway constriction
and inflammation Each dose contains 25 mcg salmeterol xinafoate and 125 mcg
fluticasone propionate Inhalers doped with Rose Bengal Dye for visualization
purposes
Test Inhaler
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Allows for precise measurements of flow concentration in all regions of the lung model
Consists of: A source that generates electromagnetic radiation A dispersion device that selects a particular
wavelength from the broad band radiation of the source
A sample area A detector to measure the intensity of radiation
2004 Mechanical & Industrial Engineering, University of Toronto
Spectrophotometer
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Available Solutions Computer / Mathematical Models
Physical Models
Twin Impinger
Cascade Impactor
Limitations
Our Goal:
Devise a physical lung model, superior to the existing models, to test pharmaceutical inhalers
2004 Mechanical & Industrial Engineering, University of Toronto
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Human Respiratory System
Mouth/Nose Trachea Bronchioles Alveoli
Alveoli
2004 Mechanical & Industrial Engineering, University of Toronto
Lung Properties
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Lung Geometry
• Weibel Model A
– Number of generations, z– Branch diameter
– Branch length
trachea
z
ddwheredzd
0
30 ,
2
1)(
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Weibels Model
Z (Branching generation)
N (z) (Number of branches) = 2 Z
d (z) (Branch diameter) = do x
2 –z/3
23 generations of bronchiole branching
Average Trachea diameter is 1.8 cm
2004 Mechanical & Industrial Engineering, University of Toronto
Lung Geometry
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Particle Deposition
• Methods and Areas of Particle Deposition
– Impaction
– Sedimentation– Diffusion
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2004 Mechanical & Industrial Engineering, University of Toronto
Weibels Model
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Average volume of inhaled air is 500cc
Average pressure difference is 2mm Hg
Approximation of airflow within the human lung:
Quiet breathing = 0.4 litres/s
Mild Exercise = 1.25 – 1.5 litres/s
2004 Mechanical & Industrial Engineering, University of Toronto
Physical Lung Properties
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Computer / Mathematical Models Not very accurate, based only on mathematical
equations No physical data to support the models Do not account for the randomness of particle flow and
deposition inside a complex organ like the human lung
Physical Models Twin Impinger Cascade Impactor
2004 Mechanical & Industrial Engineering, University of Toronto
Existing Models
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Tests the lung penetration capability of a pressurized metered dose inhaler (pMDI)
2004 Mechanical & Industrial Engineering, University of Toronto
Twin Impinger
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Twin Impinger Apparatus
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Measures the aerodynamic size distribution and mass concentration levels of solid particulates and liquid aerosols
Cascade Impactor
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Cascade Impactor Apparatus
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Other Design Concepts
• Medical Tubing Concept– Positive displacement pump– Standard medical tubing– Standard connectors
• Advantage: Ease of separation
• Concern: Flow obstruction at junctions
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Existing Solutions
• Computer/Mathematical Models– Limited to the accuracy of the governing equations– Requires experimental verification
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Twin Impinger Only 2 compartments Simplified particle flow path No flow visualization
Cascade Impactor No set path to follow No flow visualization
2004 Mechanical & Industrial Engineering, University of Toronto
Limitations
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MUSSL Lung Model Based on Direct Flow Visualization
• A transparent lung model
• Use particle deposition tracing– Ink Visualization
– X-ray Scintigraphy using Radiolabeled particles
– Planar Laser Imaging
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Design Concepts
• Expanding-Contracting Lung Design– Machined representation of lung covered
with silicon membrane– Expanded by external breathing bag– Difficult to control expansion and
contraction
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Detailed Design Description
• Drawing of lung
• Machining of lung
• Mouth-trachea induction port
• Ventilator/breathing apparatus
• Tracer dye labeled aerosol
• Filtration and resistance devices
• Testing and Apparatus Setup
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Drawing of the Lung
• AutoCAD Representation– 2-D– 8 to 9 generations– Approx. 750 branches
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Drawing of Lung
• SolidWorks 2003 Drawing
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Drawing Procedure
a) The sketch is projected to offset plane. b) The inter-planes are created.
c) Circles are drawn on the midlines. d) Circles are extruded to planes.
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Machining of Lung
• MasterCAM file conversion
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Machining of Lung
• Machining of Bronchial Tree– Completed by Excentrotech Precision Ltd.– G-code generation: MasterCAM– High-speed 5-axis CNC mill
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Machining of Lung
• Machining of Exit Channels– Completed by MIE Machine Shop– G-code generation: MasterCAM– 3-axis CNC mill
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Final Design
• Machined representation of human lung in aluminum
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Mouth-Trachea Induction Port
• Simulates the filtering effects and geometric properties of the mouth and throat
• Schematics provided by Nuclear Medicine Department at McMaster University
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Mouth and trachea induction port development and assembly
Counter bored for the insertion of the adapter Adapter to provide un obstructed/continuous flow Not a permanent fit allows switch to the clear mouth/trachea port
2004 Mechanical & Industrial Engineering, University of Toronto
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2004 Mechanical & Industrial Engineering, University of Toronto
Creating the 3-D Model
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2004 Mechanical & Industrial Engineering, University of Toronto
Design Requirements• Model must transparent to allow for easy flow
visualization to take place
• Model must be able to mimic basic mechanical proprieties of an average human lung
» Air Volume ( 500 cc )» Pressure ( 750 mmHg )
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2004 Mechanical & Industrial Engineering, University of Toronto
Construction Overview3-D Model Creation Stages
1. Construction of the wax model
2. Coating of the model with the flexible elastomer shell
3. Separation of the model from the cured flexible shell
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2004 Mechanical & Industrial Engineering, University of Toronto
Stage 1
Creating the Wax Model
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2004 Mechanical & Industrial Engineering, University of Toronto
Second Attempt: Heating of the Mold
Plate was heated above melting
temperature of the wax
Allowed for uniform cooling of wax
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2004 Mechanical & Industrial Engineering, University of Toronto
Completed Wax Model
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2004 Mechanical & Industrial Engineering, University of Toronto
Stand
Outlet port
Lung model
Mouth/trachea induction port
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Hollow, flexible cast of a human lung
According to a procedure developed at North Carolina State University
– Silicon or latex hollow cast could be used as a breathing model
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Hollow Cast Model