Choosing the right device: the case for DPIs (DDL22)

Choosing the right device
The case for DPIs

David Harris
Drug Delivery to the Lungs 22, 8th December 2011

Confidential © Team Consulting 2011: Presentation_DDL22_v1-0 slide 1 www.team-consulting.com

Choosing the right device – the case for DPIs

Where did it all begin?



First capsule DPI – First multi-unit dose DPI -
Spinhaler (Fisons) Serevent Accuhaler (GSK)

First DPI –Aerohalor
(Abbott)
The first DPI patent -
“Inhaling Apparatus”

High performance multi-unit
First DPI with a „breath-triggered‟

dose DPI – Starhaler (Sun
first Reservoir DPI – actuation mechanism – Novolizer
Turbuhaler (Astra) (Sofotec Almirall)

Pharma)
1864 1948 1967 1987 1995 2001 2011



The story behind the Spinhaler is inspiring…

• Invented by Roger Altounyan, a long-suffering
asthmatic and medical doctor
 former RAF Spitfire pilot and instructor, who saw
the potential to use a propeller in an inhaler to
deliver dry powder effectively
• He spent half a year experimenting with
prototypes in his living room ‘laboratory’
• It still didn’t work. The powder impacted on
the inside of the tube, rather than forming an
acceptable aerosol

However…


“One day he noticed that when he sucked one of the models
it vibrated and buzzed like a dentist’s drill, presumably
because the bearing was poor and rattled. Then he
wondered if this shaking might prevent the powder from
impacting. He tried it with some powder, and at last it
produced a steady and efficient inhalation. Ironically, it was
the very fault in the eccentric action of the slightly
imperfect bearing that made the little machine work.”

Rodney Dingle, Biography of Roger Altounyan



“The most exciting phrase to hear in science, the one that
heralds new discoveries, is not 'Eureka!' (I found it!) but
‘That's funny ...’”
Isaac Asimov



Why are DPIs difficult to get right?



Respirable particles are very small
• The diameter of an average human hair
is ~50 times that of a respirable drug
particle
• It’s extremely difficult to transfer energy
to disperse such fine particles efficiently
• They can easily become trapped in
fluidic boundary layers – shielded from
aerodynamic drag forces
• Large surface area to volume ratio
means that they are susceptible to
acquiring high specific charge
(electrostatic charge to mass ratio)



I asked a fluid dynamics expert, James Tibbatts (Concept Flow Ltd) how well he could simulate
an aeroplane in order to optimise efficiency and he replied with -

“You’d be able to get lift and drag coefficients to within a few
percent – but you’d need a lot of computing power.”
In contrast, I posed the same question about optimising the airway of a dry powder inhaler
and his reply was -

“Quantitatively, you can’t get any discernible accuracy at all.
Because the physics isn’t well understood you can throw all
the computing power in the world at it and not get a
meaningful solution.”



It can be done…



• Sun Pharma (with Cambridge
Consultants & Design Directions)
 8 dimensional reduced order numerical
model of DPI airway
 based upon CFD, empirical and
theoretical inputs
 successfully mapped out design space
 enabled performance optimisation +
high independence of flowrate
 future proof – easy to fine tune Conix 1
Disposable single-dose

• 3M’s Conix DPI family are all based upon
one single aerosolisation engine Conix 2
Reloadable single-dose
 three different inhaler products
 all have the same performance
Conix 3
Pre-metered multi-dose



“Remember that
all models are
wrong; the
practical
question is how
wrong do they
have to be to
not be useful”
George E. P. Box, 1987



An exciting future!
?



Semiotics – ‘the study of signs and symbols’

1 2 3

4 5 6

How is this relevant to DPIs… ?



• Huge diversity of scientific / technological
approach to inhaler design…
 but does this have to be presented as diversity of
user interactions?
• There may be an opportunity to agree a
common symbol for a key inhaler use step
 e.g. “load dose”
• There is certainly an opportunity to agree a
common approach to instructions for use

“The nice thing about standards
is that you have so many to
choose from.”
Andrew S. Tanenbaum



• The MannKind Corporation
 pursuing the delivery of inhaled
insulin - DPI product Afrezza
 which is undergoing late stage
clinical studies
• Successful treatment of diabetes CricketsTM - disposable
through the systemic delivery of
inhaled insulin would be a major
breakthrough
 potentially opening the route for
many forms of the therapeutic
delivery of new molecules
• pain management
• vaccination

What therapies will DPIs of DreamBoatsTM – reusable
the future deliver?


Acknowledgements

Many thanks to:-
• Mark Sanders, Inhalatorium for kindly providing the images of Aerohalor and Spinhaler
• John Bell, Stewart Erl Associates, for sharing his extensive insights about the early development of
the Spinhaler
• Robert N Slinn, who worked on the synthesis of analogues of cromoglycate at Fisons, for sending
me a copy of Roger Altounyan’s biography
• Hans Lundback, Astra Zeneca, for the kind provision of images of early Turbuhaler images
• David Blakey & The Device Technology Group, GSK, for kindly providing images of the original
Serevent Accuhaler
• Prashant Kane, Sun Pharma, for permission to use images of the Starhaler
(developed in collaboration with Cambridge Consultants and Design Directions)
• Jag Shur, University of Bath, for providing excellent SEMs of Salbutamol on a human hair
• James Tibbatts, Concept Flow, for the quotations and informative discussion around CFD and
reduced order numerical modelling
• Georgina Fradley, 3M, for kindly providing images of the three Conix DPI platforms
• Chad Smutney, MannKind Corporation, for the great images of their Cricket and Dreamboat
ranges of DPIs
• Julian Dixon, Team Consulting, for his input on the usability of DPIs


Choosing the right device: the case for DPIs (DDL22)

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