Issue link: https://www.e-digitaleditions.com/i/1515319
Inhalation February 2024 15 this influences drug deposition characteristics. In recently published work, we have undertaken a suite of cascade impaction measurements of various model BDP formulations in a range of propellants and compared several outcomes [19]. An ultra-low concentration of 0.05 mg/mL BDP without co- solvent was used as a model co-solvent-free solu- tion. is was compared to solution formulations of 2.0 mg/mL BDP at various ethanol concentrations. e results are shown in Table 1 [19, 23]. Data are given as the average of N = 3 replicates ±1 standard deviation. Each aerodynamic particle size distribu- tion measurement consisted of n = 24 repeated actu- ations (for co-solvent-free formulations) and n = 5 actuations (for 8% and 15% ethanol solutions). We found that HFA-152a formulations showed con- sistently lower fine particle fraction and higher actu- ator, coupler and USP throat deposition compared to analogous formulations with HFA-134a. HFO- 1234ze(E) formulations showed improved perfor- mance with respect to these metrics. e low density and higher velocity of HFA-152a results in a less sta- ble and wider spray (as indicated by spray pattern area). is likely results in greater mouthpiece depo- sition and loss in the USP throat. Conversely, the high density and lower pressure of HFO-1234ze(E) can lead to narrow plumes. While it reduces mouth- piece, coupler and throat deposition, the narrower spray and reduced mixing causes maturation to occur further from the orifice. Conclusions: Novel ways to accelerate the transition to low GWP propellants Existing in vitro test results on HFA-152a and HFO- 1234ze(E)-based formulations suggest that neither propellant is a drop-in replacement for HFA-134 or HFA-227ea, and that one does not have a deci- sive advantage over the other. HFA-152a has simi- lar molecular and chemico-physical properties to the current-generation of HFAs and may be well suited to a range of solution formulations where solubility or stability in HFO propellant is poor. However, its low density makes reformulation of suspensions chal- lenging and it produces a less stable spray that can lead to a lower fine particle fraction than HFA-134a in equivalent hardware. Its GWP is still more than 100 times that of CO 2 . HFO-1234ze(E) is an ultra- low-GWP replacement whose higher density makes it well suited to suspension formulations, but whose lower vapor pressure (and therefore spray velocity) can lead to narrower sprays with larger droplets and longer maturation length and time scales. e key finding of the preliminary in vitro studies described in this paper is that the changes required to convert pMDI formulations from current HFAs to low-GWP alternatives require careful evalua- tion, but do not represent an insurmountable bar- rier. e in vitro methods shown here may provide