A Device to Model a Human Lung to Determine the Delivery Efficiency of Inhaled Pharmaceutical Aerosols

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A Device to Model a Human Lung to Determine the
Delivery Efficiency of Inhaled Pharmaceutical
Aerosols
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• Overview

• Background
• Existing Models
• Developed Models
• Flexible Lung Model
• Rigid Lung Model
• Testing Methodology
• Model Assessment and Conclusion

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Medication Administration

• Medications are administrated by
• Oral ingestion
• Intravenous Injections
• Respiratory system (Pharmaceutical Inhalers)

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Pharmaceutical Inhalers Advantages ? 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
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Pressurized Metered Dose Inhaler (pMDI)
Breath Activated Inhaler
Pressurized Aerosol Inhaler with Spacer
Nebulizer
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

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• Spectrophotometer

• 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

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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

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Lung Properties

• Human Respiratory System
• Mouth/Nose ? Trachea ? Bronchioles ?
  Alveoli

Alveoli
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Lung Geometry

• Weibel Model A
• Number of generations, z
• Branch diameter
• Branch length

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Lung Geometry

• 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

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Particle Deposition

• Methods and Areas of Particle Deposition
• Impaction
• Sedimentation
• Diffusion

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Weibels Model
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Physical Lung Properties

• 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

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• Existing Models

• 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

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• Twin Impinger

• Tests the lung penetration capability of a
  pressurized metered dose inhaler (pMDI)

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• Twin Impinger Apparatus

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• Cascade Impactor

• Measures the aerodynamic size distribution and
  mass concentration levels of solid particulates
  and liquid aerosols

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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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• Limitations

• Twin Impinger
• Only 2 compartments
• Simplified particle flow path
• No flow visualization
• Cascade Impactor
• No set path to follow
• No flow visualization

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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
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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

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• Creating the 3-D Model

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• 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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• Construction Overview

• 3-D Model Creation Stages
• Construction of the wax model
• Coating of the model with the flexible elastomer
  shell
• Separation of the model from the cured flexible
  shell

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Stage 1 Creating the Wax Model
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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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Completed Wax Model
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Mouth/trachea induction port
Lung model
Outlet port
Stand
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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