How to engineer aerosol particle properties and biopharmaceutical performance of propellant inhalers.

Given the environmental compulsion to reformulate pressurised metered dose inhalers (pMDI) using new propellants with lower global warming potential, this study investigated how non-volatile excipients can be used to engineer aerosol particle microphysics and drug release. The dynamics of change in particle size, wetting and physical state were measured for single particles (glycerol/ethanol/beclomethasone dipropionate; BDP) in the aerosol phase at different relative humidity (RH) using an electrodynamic balance. BDP dissolution rates were compared for aerosols from pMDI containing different ratios of BDP:glycerol or BDP:isopropyl myristate (IPM). In 45 % RH, ethanol loss was followed by evaporation of condensed water to generate spherical particles with solid inclusions or compact irregular-shaped solid particles, according to the presence or absence of glycerol. In RH > 95 %, condensed water did not evaporate and BDP formed solid inclusions in water/glycerol or water droplets. Varying the non-volatile component, 0-50 % w/w, in pMDI resulted in a concentration-dependent 4-8-fold reduction in BDP dissolution rate. These findings demonstrate that non-volatile excipients provide a means of engineering aerosol properties and, modifying the rate of drug release from aerosol medicines. We also demonstrated differences between particles formed in vitro in ambient humidity versus higher humidity, more like that encountered during oral inhalation.