Innovative Drug Development Approach to Address the Transition to Low Global Warming Potential Propellant Using...

Area of Science:

• Pharmaceutical Sciences
• Environmental Science
• Respiratory Medicine

Background:

• Environmental policies are driving the development of pressurized metered-dose inhalers (pMDI) with reduced climate impact.
• Current pMDIs for asthma and COPD use hydrofluorocarbon (HFC) propellants like HFA-134a and HFA-227ea, which have high global warming potential.
• Manufacturers are shifting towards low global warming potential (LGWP) propellants, such as HFA-152a, to create more sustainable inhaler options.

Purpose of the Study:

• To report an innovative method for developing pMDI drug products utilizing LGWP propellants.
• To validate the hypothesis that pMDIs with LGWP propellants can achieve performance equivalent to those with current propellants.
• To demonstrate the comparability of a triple combination pMDI (Trimbow®) formulated with HFA-152a versus HFA-134a.

Main Methods:

• In silico mathematical modeling using proprietary Modulite® principles to predict pMDI performance.
• Validation of in silico predictions through in vitro testing, including realistic aerodynamic particle size distribution (rAPSD).
• In vivo assessment via preliminary pharmacokinetic (PK) studies in animal models and formal clinical bioequivalence (BE) studies.

Main Results:

• In silico models accurately predicted in vitro performances of the new pMDI formulations.
• rAPSD provided a more accurate prediction of aerosol distribution compared to standard APSD.
• In vitro and in vivo studies confirmed good aerodynamic performance comparability between HFA-152a and HFA-134a propellants, supporting bioequivalence.

Conclusions:

• The study successfully developed and validated a novel approach for creating pMDIs with LGWP propellants.
• The findings confirm that pMDIs using LGWP propellants can achieve comparable aerodynamic performance to those using traditional HFCs.
• This research paves the way for more environmentally sustainable pMDI treatments for asthma and COPD without compromising efficacy.