Comparison of In-Vitro Performance Characteristics of Salbutamol pMDI with Low GWP Propellant (HFA-152a) vs The Current Propellant (HFA-134a)
Ameet Sule1, Sunita Sule1, Tracey Mullington1, Arslan Khan1, Lauren Liddle1, Robert Bootle1
1H&T Presspart Inhalation Product Technology Centre, Whitebirk Industrial Estate, Blackburn
BB1 5RF, UK
Summary:
Pressurised metered dose inhalers (pMDIs) though complex systems, remain highly preferred drug delivery devices for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Low GWP propellants are now being explored to reduce the carbon footprint of the pMDI. HFA-152a and HFO-1234ze are two current low GWP alternatives. Even after almost four decades, Salbutamol is still the most sought-after short-acting beta2-adrenergic agonist as a reliever for Asthma. Along with the propellants, the container closures and formulation characteristics play an essential role in product development.
To understand the behaviour of Salbutamol API with HFA-152a and HFA-134a in a plasma-treated canister, a series of in-vitro tests were conducted at an initial time point and 12 months at ambient conditions. The test results indicated that HFA-152a is a promising potential alternative to HFA-134a as a low GWP propellant. The data generated shows a close match for fine particle dose between the two propellants with a p-value of 0.903. Modifications to actuator geometries are to be considered to allow for the differences in the physical properties of the propellants. The delivered dose performance throughout canister life showed acceptable performance for each propellant at initial and 12-month time points with no individual results exceeding ± 25% of the target dose. Due to the differences in density between the propellants, the difference in spray area is significant, with a p-value of 0.000, with HFA-152a generating a larger spray area and wider plume.
Key Message:
Salbutamol formulation in plasma-treated canisters with the new low GWP HFA-152a propellant showed acceptable performance at initial and 12 months for APSD and delivered dose. Further studies are needed to arrive at a suitable shelf life and robust product development before clinical studies can be initiated.