The study was conducted in response to amendments to the Montreal Protocol that aim to gradually phase-down the production of hydrofluorocarbons (HFCs) over the next 20 years due to their high global warming potential (GWP). This creates a need to develop pressurized metered dose inhalers (pMDIs) with lower GWP propellants.

Short-acting beta agonists, which account for half of global inhaled medications (by the number of doses prescribed), with much of this volume attributed to albuterol sulfate pMDIs. Switching existing albuterol sulfate pMDIs formulated with HFA 134a (GWP=1,300) to inhalers based on lower GWP propellants would preserve this important albuterol sulfate drug product. However, in order to be found bioequivalent, these ‘greener alternatives’ may be required to demonstrate similar regional deposition and clearance from the lung.

In this study, a suspension-only formulation containing albuterol sulfate (AS) and 1,1-Difluroethane (HFA-152a, GWP=138) was manufactured. Realistic aerodynamic particle size analysis of the sprayed product was used to predict the regional deposition of the albuterol using a one-dimensional model. In addition, drug absorption was predicted using a physiologically-based pharmacokinetic (PB-PK) model.

The suspension stability assessment of AS in liquefied HFA-152a suggested that the average floc particle size was approximately 2.0 µm and that the sedimentation time was 1.6 mins. The emitted dose of the Ventolin and albuterol HFA-152a formulation measured using cascade impaction was 111 µg and 105 µg, respectively. The mean MMAD and their standard deviations of the Ventolin and albuterol HFA-152a formulation measured using cascade impaction was 2.22 ± 0.10 µm and 2.13 ± 0.11 µm, respectively showing similar delivery and aerodynamic behavior.

The predicted regional deposition of Ventolin and the albuterol HFA-152a formulation suggested that while the central lung regional deposition was similar between both products, the extrathoracic deposition of Ventolin was lower than the albuterol HFA-152a formulation. The predicted peak plasma concentration was lower for the albuterol HFA-152a formulation than the Ventolin product, which is attributed to the lower predicted peripheral deposition of albuterol for the HFA-152a formulation compared to Ventolin.