Metered dose inhalers in the transition to low GWP propellants: what we know and what is missing to make it happen

ABSTRACT

Introduction

The urgency to replace the propellants currently in use with the new sustainable ones has given rise to the need for investigation and reformulation of pMDIs.

Areas covered

The reformulation requires in-depth knowledge of the physico-chemical characteristics of the new propellants, which impact the atomization capacity and the plume geometry. Among the investigated propellants, HFA 152a, due to its lower vapor pressure and higher surface tension compared to HFA 134a, deliver larger particles and has a higher solvent capacity toward lipophilic drugs. On the other hand, HFO 1234ze has properties more similar to HFA 134a, but showed lower reproducibility of the generated spray, indicating a possible high susceptibility to variation in the consistency of the dose delivered. In addition, the device components currently in use are compatible with the new propellants. This allowed promising preliminary results in the re-formulation of pMDIs by academia and pharma companies. However, there is little information about the clinical studies required to allow the marketing of these new products.

Expert opinion

Overall, studies conducted so far show that the transition is technically possible, and the main obstacle will be represented by the investment required to put the product on the market.

KEYWORDS:

• Metered dose inhalers
• HFA 152a
• HFO 1234ze
• inhalation product
• eco-sustainable propellants

Article highlights

• Indication of the timescales required by the regulations for the replacement of the propellants of current pMDIs with sustainable ones;

• Impact of the chemical-physical properties of the new propellants on atomization (phase I of aerosol formation);

• Description of the formulation approaches of pMDI products with HFA152a and HFO1234ze: effect on phase II of aerosol formation (droplet evaporation);

• IP landscape of patent filed focused on HFA152a and HFO1234ze;

• Overview of the regulatory aspects suggested to date and clinical trials currently underway (safety, local tolerability and PK).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank Gaetano Brambilla for his kind availability in providing valuable suggestions and comments on the manuscript.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.