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