1. The Aerosol Drug Management Improvement Team
ADMIT
Slide Deck 2018

2. Part 6
Aerosol device options
Federico Lavorini

3. Evolution of Aerosol Drug Delivery Devices
Courtesy by M. Dolovich

4. Devices generating drug aerosols
Pressurised Metered-Dose Inhalers (pMDI) with and without spacers
Breath-actuated Metered-Dose Inhalers
Dry powder inhalers (DPIs)
Soft mist inhaler (SMI)
Nebulisers

5. Formulation Components
Metering chamber
Formulation
Components
Active drug
Propellent
Co-solvent
Valve
Metering of a single dose
Pressing the stem
disconnects the metering chamber
Discharge of the dose
from the metering chamber
Courtesy by M. Dolovich

6. pMDI Technology Changes
Propellant
Suspension
CFC BDP/FP
Solution
HFA QVAR
Hardware
valves, seals, canister
Formulation
Excipients, co-solvents
Dose counter
Spacers/Valved holding chambers

7. pMDI technology changes: HFA-driven pMDIs producing extrafine particles
Low velocity “soft” spray; long plume duration
Small droplet size and high lung deposition
Clinically effective at half the dose of traditional pMDI

8. Spacers
Spacers are extensions to a pMDI with a port at one end to which the pMDI is attached, a facemask or mouthpiece being fitted at the other end
These devices constitute a volume into which the patient actuates the pMDI and from which the patient inhales without necessarily having to coordinate the two manoeuvres.

9. Categories of spacers
Open tube spacers, that simply distance the inhaler from the patient’s oropharynx
Holding chambers, which include a one-way inhalation valve, intended to retrain the aerosol within the device until the patient inhales
Reverse-flow devices, in which the spray is fired either into a collapsible bag or into a small volume through which outside air is entrained
Home-made spacer

10. Spacers increase lung deposition
When a pMDI is used alone, medicine ends up in the mouth, throat, stomach and lungs
When a pMDI is used with a spacer more medicine is delivered to the lungs
Newman SP et al. Chest 1986

11. Reduction in respirable particles
Spacers do not obviate all errors of inhalation technique
Lengthy delay between pMDI actuation
and inhalation from the spacer
Reduction in respirable particles
Firing multiple puffs into the
spacer before inhaling
Barry PW, O’Callaghan C. Brit J Clin Pharmacol , 1996

12. pMDI poor coordination
Breath-actuated metered dose inhalers
Advantages
No hand-mouth co-ordination needed
Usually higher lung deposition than a pMDI
Disadvantages
Contain propellants
“Cold Freon” effect
Only short-acting bronchodilator and BDP available
pMDI poor coordination
BA-pMDI
same patient

13. Breath-actuated pMDIs: potential clinical benefits
Review of a large number of patients in “real-life” primary care setting;
Patients using breath-actuated pMDI:
Better asthma control
Trend to fewer asthma exacerbations
Possibly used fewer healthcare resources
Price et al, Respir Med 2003; 97: 12-19

14. DPI design

15. Turbulent Energy: √P= Q x R
Mechanism of dispensing powder from a DPI
Turbulent Energy: √P= Q x R
Q=Inhalation flow,
R= Inhaler resistance

16. DPI Resistance
Handihaler 0.16
cmH2O1/2 Lmin-1
Diskus /Accuhaler 0.07 cmH2O1/2 Lmin-1
Turbohaler 0.12
Aerolizer 0.05
Inhalation Flow (L/min) 12 10 8 6 4 2 03
Pressure Drop (kPa) + -
The lower the resistance, the higher the inhalation flow
the higher the resistance, the lower the inhalation flow
Al-Showair et al Respir Med 2007

17. DPI lung dose alters with inhalation flow10 20 30 40 50 60 70 80 90
100
Inhalation Flow (l/min)
Fine Particle Dose (%)
THROAT DEPOSITION
Turbohaler
Aerolizer
Accuhaler
Palander, Clin Drug Invest 2000; Weuthen, J Aerosol Med 2002

18. Soft mist inhalers
Multi-dose inhalers containing liquid formulations similar to those in nebulisers:
Dose delivered in single breath
Propellant-free
Portable
Higher lung deposition than traditional
pMDI
Low velocity (“soft”) sprays: likely reduction in coordination problems
Only one marketed device so far: the Respimat®

19. Propellant-Free technologies under investigation (Dolovich)
The Respimat is a marriage of pMDI portability
with small-volume nebuliser ease of use.
«metered dose
liquid inhaler»

20. Nebulised aerosol is dynamic!
Nebulised aerosol size is unstable in entrained ambient air
and rapidly loses water vapour, decreasing size
Nebulised aerosol is dynamic!

21. Drug Losses with Nebulisers
Efficiency of conventional nebulizers
Drug Losses with Nebulisers
60%
60 %
40 %
60%
40 %
36%
Fill Dose
Emitted
Inhaled
Lung
Periphery
14% 6%

22. New generation nebulisers
MicroAIR U22
Pari e-flow
Aeroneb
Respimat
Developed over the past 10 years; evaluated in over 55 clinical trials in more than 1,400 subjects
Bronchodilator, steroids, Insulin, morphine, interferon
High lung deposition; portable, self-contained; EXPENSIVE

23. Breath enhanced (open vent)
Nebuliser design variations
Constant output
Breath enhanced (open vent)
Dosimetric
(breath actuated)

24. Rau JL, et al. Respir Care 2004

25. Which inhaler is right for your patient?
Inhaler devices & drugs > 250 = confusion!
Which inhaler is right for your patient?
“The proliferation of inhalation devices has resulted in a confusing number of choices for the health-care provider and in confusion for both clinicians and patients trying to use these devices correctly.”
Crompton GK et al. Respir Med, 2006

26. Conscious inhalation possible Conscious inhalation not possible
Prescription of inhalers in asthma and COPD: towards a rational, rapid and effective approach
Patient
Conscious inhalation possible
Conscious inhalation not possible
Inspiratory flow >30 L/min
Inspiratory flow <30 L/min
Hand breath
coordination
Hand breath discoordination
Hand breath coordination
pMDI + spacer
DPI
Ba-pMDI
pMDI
SMI
pMDI +/- spacer
pMDI +spacer
Nebuliser
P.N.R. Dekhuijzen, W. Vincken, J.C. Virchow, N. Roche, A. Agusti, F. Lavorini, W.M. van Aalderen, D. Price - Respiratory Medicine (2013) 107,