Do In-vitro dissolution rates differ between beclomethasone dipropionate particles generated from solution-based pMDIs formulated with HFA134a, HFA152a and HFO1234ze(E) propellants?
Hui Xin Ong1,2, Nirmal Marasini1, Lingzhe Rao3, Daniel Duke3, Damon Honnery3, Stephen W. Stein4, Benjamin Myatt5, Phil Cocks5 & Paul Young1,6
1 Respiratory Technology, Woolcock Institute of Medical Research, Glebe, Sydney, NSW 2037, Australia
2Macquarie Medical School, Faculty of Medicine, Healthy and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia
3Laboratory for Turbulence Research in Aerospace & Combustion (LTRAC), Department of Mechanical & Aerospace Engineering, Monash University, Melbourne, Australia
4Kindeva Drug delivery, 11200 Hudson Road, Woodbury, MN 55129
5Kindeva Drug Delivery, Charnwood Campus, 10 Bakewell Road, Loughborough, United Kingdom, LE11 5RB
6Department of Marketing, Macquarie Business school, Macquarie University, Sydney, NSW 2109, Australia
Summary
The switch from Hydrofluoroalkane 134a (HFA134a), with relatively high global warming potential (GWP), traditionally used in pressurised metered-dose inhalers (pMDI) to low GWP propellants HFO1234ze(E) and HFA152a is currently underway, posing numerous scientific questions and challenges to formulation development. This study aims to investigate the morphological properties of maturated beclomethasone dipropionate (BDP) particles generated from solution-based pMDIs formulated with three different propellants and the impact of these characteristics on in-vitro drug dissolution. To achieve this, a modified Andersen Cascade Impactor (ACI) that incorporates SnapwellTM inserts on a 3D-printed ACI plate was used to deposit and study the aerosol particles of specific aerodynamic size ranges produced from the three different pMDI formulations. The Snapwell insert was then used as a micro-dissolution apparatus. The dissolution rate of the drug particles over four hours showed the following rank order: HFA134a > HFO1234ze(E) > HFA152a. This could be attributed to the morphologies of the drug particles found on stage 5 of the ACI where HFA134a produced maturated particles with the smallest geometric size of both the corrugated/rough (1.45 µm) and smooth/spherical particles (0.78 µm) with a higher percentage (53%) of rough/irregular particles in comparison with HFO1234ze(E) and HFA152a formulations. From these initial findings, a thorough investigation into the morphology and dissolution performance in combination with detailed physicochemical profiles and aerosol performance of the particles is required to understand the effect of the new propellants when formulating next the generation low GWP pMDIs.