Issue link: https://www.e-digitaleditions.com/i/1515319
Inhalation February 2024 13 scale, high-magnification imaging systems capa- ble of collecting large amounts of time-resolved data are required. We have undertaken a large-scale parametric study of pMDI plume dynamics utiliz- ing an ultra-high-speed imaging approach [19]. In the data shown in this article, a conventional Kin- deva actuator with 0.3 mm orifice and conventional FEP-coated aluminum canisters with 50 µL Bespak metering valves were used (King's Lynn, Bergen Way, UK); these were identical across all tests. A range of formulations were studied containing 0%, 8% and 15% ethanol co-solvent with 2.1 mg/mL beclometh- asone dipropionate (BDP) in propellant HFA-134a, HFA-152a or HFO-1234ze(E). A sub-microsecond pulsed LED backlight was used to uniformly illuminate the near orifice region of the pMDI spray, which was accessed by cutting a view- ing window into the side of the mouthpiece. A high- speed camera recorded video with a magnification of 31 µm/pixel at up to 140,000 frames per second. A sample high-speed image is shown in the upper panel of Figure 3. Spray measurements were repeated 15-60 times with 2,000-14,000 frames per spray, resulting in more than 100,000 images per formu- lation, in order to achieve sample size-independent statistics. From this large, multi-terabyte database, statistical analyses of plume structure were under- taken to obtain both the temporal stability across the ese properties determine the amount of evapo- ration and expansion that occur as the formulation passes through the orifice and forms the initial spray. ese key chemico-physical properties can vary con- siderably when the propellant or co-solvent level is altered. As the droplets break apart and coalesce, droplet size tends to an equilibrium that depends on surface tension [15]. Complex thermal and turbulent droplet mixing effects are also involved. One of the major challenges in the implementa- tion of low-GWP propellants for pMDIs is that each has a unique set of chemico-physical proper- ties, with at least one or of more of these being suboptimal when compared to current-generation propellants. For example, HFA-152a has a high vapor pressure but a low liquid density relative to HFA-134a, which allows the spray to expand more widely, resulting in increased mouthpiece deposi- tion [18]. Conversely, HFO-1234ze(E) has a low vapor pressure but high density relative to HFA- 134a, which produces a narrow plume, leading to fewer and larger droplets [10, 19]. e structural differences between pMDI plumes with different propellants can be subtle, as they occur close to the orifice where the fluid is moving with high velocity [20]. In this region, the relevant length and time scales are on the order of microns and microseconds. To investigate the flow at such HFA-134a HFA-227 HFA-152a HFO-1234ze(E) GWP, kg CO 2 -equivalent 1430 3220 124 7 Saturated vapor pressure at 25º C (SVP) 6.7 atm. 4.7 atm 5.6 atm. 4.6 atm. Specific gravity (liquid phase at 25º C) 1.21 1.41 0.91 1.17 Theoretical stable droplet size at 25º C 5.7 µm 4.9 µm 9.7 µm 7.5 µm Fine particle fraction 0.05 mg/mL BDP in propellant only 88.5% - 70.7% 93.6% 2.0 mg/mL BDP in 8% w/w ethanol 55.7% - 51.3% 60.7% 2.0 mg/mL BDP in 15% w/w ethanol 54.2% - 50.1% 56.6% Actuator, coupler, and throat deposition 0.05 mg/mL BDP in propellant only 32.3% - 40.5% 30.8% 2.0 mg/mL BDP in 8% w/w ethanol 51.7% - 64.7% 52.6% 2.0 mg/mL BDP in 15% w/w ethanol 50.3% - 54.1% 46.8% Spray pattern area at 60mm 0.05 mg/mL BDP in propellant only 589 ± 82 mm 2 - 610 ± 68 mm 2 474 ± 31 mm 2 2.0 mg/mL BDP in 15% w/w ethanol 526 ± 24 mm 2 - 573 ± 22 mm 2 466 ± 26 mm 2 Table 1 Key chemico-physical properties of various propellants, and typical APSD results obtained with model suspension and solution betamethasone dipropionate (BDP) formulations made with them. Background color density indicates relative improvement (green) or deterioration (orange) relative to HFA-134a. Adapted with permission from reference 19.