Development and in vitro evaluation of solution-based pressurized metered-dose inhaler formulations using green...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Pressurized metered-dose inhalers (pMDIs) are transitioning to low-global warming potential (GWP) propellants.
• Hydrofluoroalkanes (HFAs) like HFA134a are being replaced by alternatives such as HFO1234ze(E) and HFA152a.
• Understanding propellant impact on drug particle behavior is crucial for inhaler formulation development.

Purpose of the Study:

• To investigate the influence of different propellants on the physicochemical behavior of maturated beclomethasone dipropionate (BDP) particles.
• To assess how low-GWP propellants affect BDP particle morphology and dissolution characteristics.
• To provide insights into propellant selection for future pMDI formulations.

Main Methods:

• Physicochemical analysis of BDP particles aerosolized from pMDIs with various propellants.
• Dissolution methodology to evaluate drug release rates.
• Morphological analysis using Anderson Cascade Impactor (ACI) stage 5 collection.

Main Results:

• Aerodynamic particle size distributions (MMAD) were comparable across formulations (~1.25 μm).
• HFA134a yielded a higher proportion of irregular-shaped BDP particles (53.0%) with smaller geometric size (1.45 μm).
• In vitro dissolution rate followed the order: HFA134a > HFO1234ze(E) > HFA152a, correlating with particle morphology and increased specific surface area.

Conclusions:

• Propellant choice influences the morphology and geometric size of maturated BDP particles.
• Differences in particle shape and size affect the in vitro dissolution behavior of BDP.
• Findings highlight the importance of propellant selection in pMDI formulation optimization for drug delivery.