Solubility of Beclomethasone Dipropionate in Metered Dose Inhaler Propellants and Ethanol Cosolvent Mixtures

The switch from Hydrofluoroalkane 134a (HFA-134a), with relatively high global warming potential (GWP), traditionally used in pressurised metered-dose inhalers (pMDIs) to low GWP propellants HFO-1234ze(E) or HFA-152a is currently underway, posing numerous scientific questions and challenges to formulation development. This study aims to assess the potential use of HFA-152a and HFO-1234ze(E) as alternative propellants to HFA-134a in an effort to reduce the carbon footprint of MDIs, while maintaining their beneficial properties for patient care. To transition to these lower GWP propellants, it is essential to first understand their fundamental physical properties and how they compare to HFA-134a. This study focuses on assessing the solubility of beclomethasone dipropionate (BDP) in mixtures of these different propellants with varying concentrations of ethanol as a co-solvent, using an established solubility apparatus. Ethanol concentrations ranging from 0% w/w to 20% w/w were investigated and the saturated solubility of BDP was evaluated after 7 days shaking at 25°C. Results demonstrated a positive relationship between increasing ethanol concentration and BDP solubility. Solubility of BDP in HFA-152a/ethanol mixtures was higher when compared to HFA-134a/ethanol and HFO-1234ze(E)/ethanol mixtures.