Evaluating MDI Performance in the Propellant Transition Era: Formulation, Device and Analytical Insights
Silva L, Shur J, Tran CH, Deraime G, Zapata del Baño A, Behem P, Aurore P, Vicenty M, Grosjean B, Han L, Newman B, Bielski E.
Respiratory Drug Delivery 2026. Volume 1, 2026: 20-0.
Abstract:
The transition of pressurized metered dose inhalers (pMDIs) from established hydrofluoroalkane (HFA) propellant systems to next generation propellants (NGPs) introduces significant technical challenges related to formulation behavior, aerosol generation, and device compatibility. Differences in density, vapor pressure, and evaporation kinetics impact suspension stability, atomization efficiency, delivered dose (DD), and regional deposition. These changes complicate the demonstration of comparability with existing marketed products and necessitate the use of sensitive and predictive in vitro methodologies beyond traditional compendial testing.
Recent US Food and Drug Administration (FDA) product-specific guidances (PSGs) include options for evaluating bioequivalence (BE) for potential generic pMDI products, where realistic aerodynamic particle size distribution (rAPSD) is included as a key test to evaluate performance of inhaled formulations. Building upon prior discussions at Center for Research on Complex Generics (CRCG) 2024 workshop and methodological advances presented at International Society for Aerosols in Medicine (ISAM) 2025, this article examines the utility and discriminating ability of several in vitro methods included in pMDI PSGs to evaluate NGP-based albuterol sulfate suspension pMDIs manufactured under an FDA-funded research project. This study provides a systematic in vitro characterization of how NGPs, surfactant choice, and actuator orifice diameter jointly govern oropharyngeal deposition and fine particle delivery for albuterol MDIs.
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