Flash Atomization in a Model System Representing Pressurized Metered Dose Inhaler Sprays Farzin M. Shemirani 1 , Tanya K. Church 2 , David A. Lewis 2 ,Warren H. Finlay 1 , Reinhard Vehring 1 1 Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada 2 Chiesi Ltd. Inc., Chippenham, UK Introduction Theoretical Results Acknowledgement References + Theory In the current study, the time scales involved in flash atomization as the main mechanism to produce a wide variety of droplet sizes in metered dose inhalers is studied theoretically and experimentally. ❑ It is observed that propellant selection affects onset of flash atomization in propellant jets. HFA134a jets tend to flash at lower temperatures compared to HFA227ea jets. Addition of ethanol postpones flash atomization. ❑ Evaporative cooling in propellant droplets is both affected by the choice of mixture and droplet size. It is observed theoretically that HFA134a droplets cool down faster than HFA227ea droplets. At smaller droplet sizes evaporative cooling is accentuated, and it is believed to be due to higher surface to volume ratio of smaller droplets, and lower heat capacity of smaller droplets compared to large ones. ❑ The current results show that for each formulation at ambient temperature, there exists a characteristic jet (droplet) diameter below which breakup into smaller duplets due to flash atomization does not occur. ❑ The current results may be useful in efforts aimed at finding new propellants and formulations to produce finer MDI sprays for more effective pulmonary drug delivery. Conclusion ❑ A single HFA droplet with one spherical bubble at its center is considered. The behaviour of the droplet is determined by two competing parameters; bubble growth rate and droplet evaporation rate. The bubble growth rate controls the onset of flash atomization. Droplet evaporation rate controls the cooling rate of the droplet which eventually terminates flash atomization. ❑ Conservation equations for mass and energy were solved simultaneously to determine droplet diameter and droplet temperature as a function of time. ❑ Bubble radius is calculated as a function of time using Mikic’s (1970) solution of the Rayleigh-Plesset equation. The underlying cause of the atomization mechanism producing pressurized metered dose inhaler (pMDI) sprays is thought to be flash atomization. Flashing starts by forming nuclei that can develop into rapidly growing vapour bubbles which can disintegrate the liquid volume once they reach a sufficient size. Propellant evaporation impedes flash atomization due to evaporative cooling which leads to a decrease in propellant vapour pressure within the bubble. In the current study, the time scales involved in bubble growth and evaporative cooling are investigated theoretically and experimentally. 10 -2 10 -1 10 0 10 1 10 -2 10 -1 10 0 10 1 10 2 10 3 HFA134a 20 o C HFA227ea 20 o C HFA134a -26.1+1.0 o C HFA227ea -16.5+1.0 o C 10 -1 10 0 10 1 10 2 -30 -25 -20 -15 -10 -5 0 5 10 15 20 HFA134a d 0 =10 μ m HFA134a d 0 =5 μ m HFA227ea d 0 =10 μ m HFA227ea d 0 =5 μ m Figure 1: Bubble diameter vs. time for bubbles in HFA134a and HFA227ea at different temperatures. Figure 2: Droplet temperature as a function of time for HFA134a and HFA227ea droplets with different initial diameters 10 15 20 25 30 35 40 0 5 10 15 20 25 30 Jet diameter (μm) Temperature (°C) HFA134a HFA227ea HFA134a+20% w/w ethanol ❑ Finlay WH: The Mechanics of Inhaled Pharmaceutical Aerosols : an Introduction. San Diego: Academic Press; 2001. ❑ Brennen CE: Cavitation and Bubble Dynamics. New York: Oxford University Press; 1995. ❑ Mikic BB, Rohsenow WM, Griffith P: On Bubble Growth Rates. International Journal of Heat and Mass Transfer 1970, 13: 657. The authors would like to thank Chiesi Ltd for their support of this study. (a) (b) Figure 3: Images of HFA jets: (a) jet below flashing temperature, characterized as being thin and steady (b) spray above flashing temperature, characterized as being Figure 4: Transition temperature of HFA and HFA-ethanol jets from non-flashing to flashing. Vertical error bars represent the deviation of the orifice diameters from their nominal ones. + Experiment ❑ A custom atomizer assembly comprising a high pressure liquid handling system as well as a temperature control circuit was used to produce cylindrical jets emerging from micro-orifices as an experimental model system. ❑ Orifice diameters used were: 5, 10, 15, 20, and 25 µm. ❑ The initial temperature of the jet was controlled in the range of 5 to 25 °C. The jet temperature was then increased gradually to the point when transition of the jet from a steady thin jet to a flashing unsteady expanded jet was visible . ❑ The liquids used were (a) HFA134a, (b) HFA134+20%w/w ethanol, and (c) HFA227ea Experimental Results Bubble Growth Evaporation Cooling Isothermal Respiratory Drug Delivery 2014, Puerto Rico
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Flash Atomization in a Model System Representing Pressurized Metered Dose Inhaler Sprays
Farzin M. Shemirani1, Tanya K. Church2, David A. Lewis2,Warren H. Finlay1, Reinhard Vehring1 1Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada
2Chiesi Ltd. Inc., Chippenham, UK
Introduction Theoretical Results
Acknowledgement
References
+
Theory
In the current study, the time scales involved in flash atomization as the main mechanism to produce a wide variety of droplet sizes in metered dose inhalers is studied theoretically and experimentally. !
❑ It is observed that propellant selection affects onset of flash atomization in propellant jets. HFA134a jets tend to flash at lower temperatures compared to HFA227ea jets. Addition of ethanol postpones flash atomization. !
❑Evaporative cooling in propellant droplets is both affected by the choice of mixture and droplet size. It is observed theoretically that HFA134a droplets cool down faster than HFA227ea droplets. At smaller droplet sizes evaporative cooling is accentuated, and it is believed to be due to higher surface to volume ratio of smaller droplets, and lower heat capacity of smaller droplets compared to large ones. !
❑The current results show that for each formulation at ambient temperature, there exists a characteristic jet (droplet) diameter below which breakup into smaller duplets due to flash atomization does not occur. !
❑The current results may be useful in efforts aimed at finding new propellants and formulations to produce finer MDI sprays for more effective pulmonary drug delivery. !!
!
Conclusion
❑ A single HFA droplet with one spherical bubble at its center is considered. The behaviour of the droplet is determined by two competing parameters; bubble growth rate and droplet evaporation rate. The bubble growth rate controls the onset of flash atomization. Droplet evaporation rate controls the cooling rate of the droplet which eventually terminates flash atomization. !
❑ Conservation equations for mass and energy were solved simultaneously to determine droplet diameter and droplet temperature as a function of time. !
❑ Bubble radius is calculated as a function of time using Mikic’s (1970) solution of the Rayleigh-Plesset equation.
The underlying cause of the atomization mechanism producing pressurized metered dose inhaler (pMDI) sprays is thought to be flash atomization. Flashing starts by forming nuclei that can develop into rapidly growing vapour bubbles which can disintegrate the liquid volume once they reach a sufficient size. Propellant evaporation impedes flash atomization due to evaporative cooling which leads to a decrease in propellant vapour pressure within the bubble. In the current study, the time scales involved in bubble growth and evaporative cooling are investigated theoretically and experimentally.
10-2
10-1
100
101
10-2
10-1
100
101
102
103
time (µs)
bubb
le d
iam
eter
(µ
m)
HFA134a 20oCHFA227ea 20oCHFA134a -26.1+1.0oCHFA227ea -16.5+1.0oC
10-1
100
101
102
-30
-25
-20
-15
-10
-5
0
5
10
15
20
time (µs)
tem
pera
ture
(o C)
HFA134a d0=10 µmHFA134a d0=5 µmHFA227ea d0=10 µmHFA227ea d0=5 µm
Figure 1: Bubble diameter vs. time for bubbles in HFA134a and HFA227ea at different temperatures.
Figure 2: Droplet temperature as a function of time for HFA134a and HFA227ea droplets with different initial diameters
10 15 20 25 30 35 400
5
10
15
20
25
30
Jet d
iam
eter
(µm
)
Temperature (°C)
HFA134a HFA227ea HFA134a+20% w/w ethanol
❑ Finlay WH: The Mechanics of Inhaled Pharmaceutical Aerosols : an Introduction. San Diego: Academic Press; 2001.
❑ Brennen CE: Cavitation and Bubble Dynamics. New York: Oxford University Press; 1995.
❑ Mikic BB, Rohsenow WM, Griffith P: On Bubble Growth Rates. International Journal of Heat and Mass Transfer 1970, 13: 657.
The authors would like to thank Chiesi Ltd for their support of this study.
(a) (b)
Figure 3: Images of HFA jets: (a) jet below flashing temperature, characterized as being thin
and steady (b) spray above flashing temperature, characterized as being
Figure 4: Transition temperature of HFA and HFA-ethanol jets from non-flashing to flashing. Vertical error bars
represent the deviation of the orifice diameters from their nominal ones.
+
Experiment
❑ A custom atomizer assembly comprising a high pressure liquid handling system as well as a temperature control circuit was used to produce cylindrical jets emerging from micro-orifices as an experimental model system. !
❑ Orifice diameters used were: 5, 10, 15, 20, and 25 µm. !
❑ The initial temperature of the jet was controlled in the range of 5 to 25 °C. The jet temperature was then increased gradually to the point when transition of the jet from a steady thin jet to a flashing unsteady expanded jet was visible . !
❑ The liquids used were (a) HFA134a, (b) HFA134+20%w/w ethanol, and (c) HFA227ea
Experimental Results
Bubble Growth
Evaporation
Cooling
Isothermal
Respiratory Drug Delivery 2014, Puerto Rico
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