Transcript Final Presentation - University of Pittsburgh

University of Pittsburgh
Senior Design – BioE 1160/1161
Novel Design of a Dry Powder
Inhaler (DPI) for the Treatment of
Acute Asthmatic Episodes
Annemarie K. Alderson
Anindita Saha
Stephanie T. Shaulis
Robert J. Toth
April 18, 2005
Mentor: Timothy E. Corcoran, Ph.D
Presentation Outline
•
•
•
•
•
•
•
Background
Problem Statement
Project Goals
Design Considerations
Prototype Development
Testing
Final Design
Background
• Asthma
• Immunologic condition
• Causes inflammation
• Increased resistance to airflow
• Due to smooth muscle constriction
• Non-specific chemical/physical triggers
• Induces hyper-reactivity
• American Lung Association estimates 20
million Americans suffer from some form of
asthma
Problem Statement
Current treatment technologies do not
adequately meet the needs of asthmatics
who suffer from minor bronchial constrictions
during physical activity
• Rescue medications
• Delivered by metered dose inhalers (MDI)
• Use CFC propellants
• Inefficient drug deposition
•
•
•
•
Complex shapes
Inefficient portability
Utilize rigid materials of construction
Precise patient coordination required
• Dispensing and inhalation
Boehringer Ingelheim, Inc.
Project Goals
• To design and develop a dry-powder, singledose, disposable inhaler
• To create a prototype that is self contained,
ruggedly constructed, lightweight, small,
ergonomically designed, and portable
• To be used by asthmatic individuals who
desire a temporary alternative to traditional
devices during physical activity
Design Considerations
• Dry powder inhaler over metered
dose inhaler
• Device load dosage of 25 ± 1 mg
• Albuterol sulfate as bronchiodilator
• Lactose as excipient
• Test drug: 70% lactose, 30%
micronized atropine
• Optimum transport of medication
to bronchioles
• 5 μm particle size
• Effective dispersion
© McGraw-Hill Companies, Inc
Design Considerations
© McGraw-Hill Companies, Inc
Heyder J, et al. Deposition of particles in human respiratory tract in the size range of 0.005-15 µm. J Aerosol Sci; 17: 811–25.
Design Considerations
• Anthropometric constraints for mouthpiece
and device body
• Average inspiration flow of 30-100 L/min for
inhalation drug therapy1
• Material of construction-low density
polyethylene
1Corcoran,
et al. Unpublished data.
Iterative Design Process
• Create solid model (SolidWorks)
• Perform CFD (COSMOS)
•
•
•
•
Turbulent / time-independent simulation
Physiologic boundary conditions
Bulk flow convergence parameter
Obtain aerosol dynamics within device consistent with 5
m particle deposition
• Modify/refine the model
• Re-perform CFD testing
• Continue cycle until acceptable solid model
completed
Prototype Development Summary
• 10 solid models developed
• Initial CFD indicated rotational flow
• Inefficient at dispersing and depositing micronsized particles
• Rotation due to boundary conditions
• Outlet volumetric flow vs. outlet pressure
• 60 L/min vs. 1 mmHg below ambient P
• Improved boundary conditions implemented
• Bulk flow patterns observed
• Model-8 rapid prototyped through
Quickparts.com
Initial CFD Model
Model-8
Rein = 10307
Rebody = 3436
Flow = 32.5 L/min
Prototype (Model-8)
Methods Used to Test Performance
Vacuum line
Prototype
Diffractive Laser Detector
Laser aperture
Inlet port
Testing Results
Volume (%) of Blend from Vial
100
90
80
70
60
50
40
30
20
10
0
34%
0.1
1
10
Particle Diameter (um)
Flow rate from vacuum line ~ 44 L/min
100
Testing Results
Volume (%) of Blend from Inhaler
100
90
80
70
60
50
40
30
20
10
0
11%
0.1
1
10
Particle Diameter (um)
Flow rate through device ~8 L/min
100
1000
Device Modifications
• Inadequate flow through device
• Increase diameter of pressure opening
• 2 mm  3 mm
• Add second opening
• Incorporate modifications into models 9 and 10
Model-10
Rein = 13743
Rebody = 8671
Flow = 42.4 L/min
Model-10 Prototype
Testing Results
Volume (%) of Blend from Redesigned Inhaler- First
Run
100
90
80
70
60
50
40
30
20
10
0
51%
0.1
1
10
Particle Diameter (um)
Flow rate through device ~38 L/min
100
Testing Results
Volume (%) of Blend from Redesigned InhalerSecond Run
100
90
80
70
60
50
40
30
20
10
0
63%
0.1
1
10
Particle Diameter (um)
Flow rate through device ~38 L/min
100
Conclusions
• Particle dispersion under 5µm observed
• Separation of drug and excipient
• Indicative of effective drug deposition
• Flow through device consistent with
physiological inspiration levels
• Range covers healthy and asthmatic individuals
• Prototype performance consistent with design
specifications
Acknowledgements
• Dr. Timothy Corcoran & Amy Marcinkowski
• Drs. Hal Wrigley & Linda Baker
• Mark Gartner
• Department of Bioengineering
Questions?
Materials Selection
Plastics Comparison
Plastic Type
Density (g/cc)
Impact Strength
(J/cm)
Rockwell Hardness
[R]
ABS
1.08
6.40
115
LD-polyethylene
0.91
6.94
60
PET
1.30
1.40
110
Polypropylene
1.07
11.50
91
Polystyrene
1.00
2.94
75
PVC
1.37
13.90
80
ABS/PVC Blend
0.98
12.50
102
Note: Heat sealing properties of LDPE would contribute to the sealing/activation mechanism
Quickparts prototype material 1.12 g/cc
Regulatory Information
• Inhalers are regulated by the FDA’s Center for
Drug and Evaluation Research
• FDA regulations
• Drug product
• Components and composition
• Specs for formulation components
• Manufacturers and method(s) of manufacture and
packaging
• Specifications for the drug product
• Container and closure systems
• Drug product stability
• Drug product characterization studies
• Labeling considerations
Human Factors Analysis
• Ergonomic considerations in design
• No sharp edges or corners
• Hand force required to grip negligible
• Anthropometric data of 5% female to 95%
compared
• Basic motor skill use needed to operate
• Simple design for ease of operation
• Lightweight for ease of portability
Project Breakdown
• Anindita
• Anthropometric
constraints
• Regulatory
information
• DHF
• Annemarie
• Robert
• Solid model
development
• CFD simulation
• Design report
document
• Stephanie
• Materials selection
• Flow inhalation
• Aesthetics
• DHF
• Drug dosage size
• Testing
• DHF
Model-3
Model-6
Model-7
Model-9