The pharmaceutical inhalation industry stands at a pivotal crossroads. After decades of relative stability following the phase-out of CFCs in the 1990s, a second major transition is underway, this time driven by the urgent need to mitigate climate change. The move toward low-global-warming-potential (LGWP) propellants such as HFA152a and HFO-1234ze(E) represents not just an environmental imperative, but also an enormous opportunity to rethink how we develop, evaluate, and deliver pressurised metered-dose inhalers (pMDIs) to patients worldwide.
This article explores the significance of the shift to LGWP propellants, early performance data generated through the pioneering work of Proveris Laboratories and H&T Presspart, and the broader implications for product development, regulatory strategies, and patient access.
A Turning Point for pMDIs
pMDIs have long been a cornerstone of respiratory care, offering portable, fast-acting relief for asthma and chronic obstructive pulmonary disease (COPD) patients. However, their environmental impact, stemming primarily from their hydrofluoroalkane (HFA) propellants, notably HFA134a and HFA227, has come under increased scrutiny. These HFAs, although ozone-safe compared to CFCs, have high global warming potentials (GWP >1300), far exceeding carbon dioxide.
Enter the next generation: LGWP propellants, such as HFA152a and HFO1234ze, have GWPs below 150, making them eco-friendly alternatives for inhalers. While they address critical environmental concerns, their adoption demands careful evaluation of their physical properties and effects on inhaler performance to ensure effectiveness and safety.
These new propellants have distinct physicochemical profiles compared to legacy HFAs. As a result, they influence critical pMDI attributes, including aerosol generation, droplet size distribution, spray force, and patient deposition patterns, all of which directly impact drug delivery efficiency and therapeutic outcomes.
The Challenges of LGWP Propellants
Despite promising data, transitioning to LGWP propellants presents real technical hurdles, including increased volatility. HFA152a has a boiling point of -24.7°C, compared to -26.2°C for HFA134a, but its lower molecular weight (~66 g/mol vs. ~102 g/mol) affects vapor pressure and aerosolisation behaviour. This can influence plume geometry, droplet velocity, and drug particle size – factors critical for efficient lung deposition.
