In-vitro Evaluation of Solution Pressurised Metered Dose Inhaler Sprays with Low-GWP Propellants

Area of Science:

• Pharmaceutical Sciences
• Inhalation Technology
• Environmental Science

Background:

• Pressurized metered dose inhalers (pMDIs) are transitioning from high Global Warming Potential (GWP) propellants like HFA134a to low-GWP alternatives such as HFA152a and HFO1234ze(E).
• This shift presents challenges in maintaining consistent product performance and in-vitro bioequivalence due to altered propellant physicochemical properties.

Purpose of the Study:

• To investigate the impact of low-GWP propellants (HFA152a, HFO1234ze(E)) on pMDI performance compared to HFA134a.
• To evaluate aerodynamic particle size distribution (APSD) and plume characteristics using equivalent pMDI hardware and formulations.

Main Methods:

• Utilized aerodynamic particle size distribution (APSD) measurements, laser diffraction, and high-speed imaging.
• Compared HFA134a, HFA152a, and HFO1234ze(E) solution formulations of beclomethasone dipropionate.
• Investigated propellant-only placebos, cosolvent-free solutions, and ethanol solutions (8% and 15% w/w).

Main Results:

• HFA152a formulations showed increased drug deposition and less stable, repeatable plumes compared to HFA134a.
• HFO1234ze(E) formulations exhibited APSD performance comparable to HFA134a, with slower plume spread.
• The addition of ethanol moderated differences between propellants, influencing plume characteristics.

Conclusions:

• Plume stability and shot-to-shot repeatability are key factors influencing formulation differences, especially ex-mouthpiece.
• Modifications to actuator orifice and mouthpiece geometries may improve in-vitro bioequivalence for low-GWP pMDIs.
• Formulation and device design adjustments can manage performance differences, providing benchmark data for future low-GWP pMDI development.