inhaler testing machine
TRANSCRIPT
2004 Mechanical & Industrial Engineering, University of Toronto
A Device to Model a Human Lung to Determine the Delivery Efficiency of Inhaled
Pharmaceutical Aerosols
Background Existing Models Developed Models
Flexible Lung ModelRigid Lung Model
Testing Methodology Model Assessment and Conclusion
2004 Mechanical & Industrial Engineering, University of Toronto
Overview
Medications are administrated by: Oral ingestion
Intravenous Injections
Respiratory system (Pharmaceutical Inhalers)
2004 Mechanical & Industrial Engineering, University of Toronto
Medication Administration
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
Inhalers
Breath Activated Inhaler
Nebulizer
Pressurized Metered
Dose Inhaler (pMDI)
Pressurized Aerosol
Inhaler with Spacer
Dry Powder Inhaler (DPI)
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
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
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
Human Respiratory System
Mouth/Nose Trachea Bronchioles Alveoli
Alveoli
2004 Mechanical & Industrial Engineering, University of Toronto
Lung Properties
Lung Geometry
• Weibel Model A
– Number of generations, z– Branch diameter
– Branch length
trachea
z
ddwheredzd
0
30 ,
2
1)(
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
Particle Deposition
• Methods and Areas of Particle Deposition
– Impaction
– Sedimentation– Diffusion
2004 Mechanical & Industrial Engineering, University of Toronto
Weibels Model
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
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
Tests the lung penetration capability of a pressurized metered dose inhaler (pMDI)
2004 Mechanical & Industrial Engineering, University of Toronto
Twin Impinger
Twin Impinger Apparatus
Measures the aerodynamic size distribution and mass concentration levels of solid particulates and liquid aerosols
Cascade Impactor
Cascade Impactor Apparatus
Other Design Concepts
• Medical Tubing Concept– Positive displacement pump– Standard medical tubing– Standard connectors
• Advantage: Ease of separation
• Concern: Flow obstruction at junctions
Existing Solutions
• Computer/Mathematical Models– Limited to the accuracy of the governing equations– Requires experimental verification
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
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
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
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
Drawing of the Lung
• AutoCAD Representation– 2-D– 8 to 9 generations– Approx. 750 branches
Drawing of Lung
• SolidWorks 2003 Drawing
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.
Machining of Lung
• MasterCAM file conversion
Machining of Lung
• Machining of Bronchial Tree– Completed by Excentrotech Precision Ltd.– G-code generation: MasterCAM– High-speed 5-axis CNC mill
Machining of Lung
• Machining of Exit Channels– Completed by MIE Machine Shop– G-code generation: MasterCAM– 3-axis CNC mill
Final Design
• Machined representation of human lung in aluminum
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
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
2004 Mechanical & Industrial Engineering, University of Toronto
Creating the 3-D Model
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 )
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
2004 Mechanical & Industrial Engineering, University of Toronto
Stage 1
Creating the Wax Model
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
2004 Mechanical & Industrial Engineering, University of Toronto
Completed Wax Model
2004 Mechanical & Industrial Engineering, University of Toronto
Stand
Outlet port
Lung model
Mouth/trachea induction port
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
Hollow Cast Model