Feasibility Development of Salbutamol Sulphate Pressurized Metered Dose Inhalers using a Low Global Warming Potential Propellant 1,3,3,3-Tetrafluoropropene (HFO1234ze)
Lei Mao, Nischal Pant, Danielle Sousa, Emily Humphreys, Danny Anderson, Ben Rinne
Recipharm Laboratories, Morrisville, North Carolina, 27560, USA
Summary
A feasibility study was conducted to develop salbutamol sulphate (SS) pressurized metered dose inhalers (pMDIs) using a low global warming potential (GWP) propellant 1,3,3,3-Tetrafluoropropene (HFO1234ze) and novel Bespak valves developed by Recipharm to match Ventolin® performance. The formulations containing SS and HFO1234ze with and without ethanol (2%) were prepared manually using coated aluminium cans. The pMDIs were tested along with Ventolin® for through life delivered doses (DD), aerodynamic particle size distribution (APSD), spray pattern (SP), plume geometry (PG), assay, impurities, moisture and leak rate. The formulation containing 2% ethanol gave a consistent DD through inhaler life but a high induction port and low stage deposition when tested using the Next Generation Pharmaceutical Impactor (NGI). Formulations without ethanol showed variable DD through inhaler life. Investigation is ongoing to understand whether this was attributed to the formulations or inhaler handling during testing. NGI results showed that the formulations without ethanol gave the same percentage deposition on the induction port but slightly higher stage 3 and 4, and lower stage 5,6,7 deposition which can be corrected by adjusting the particle size of the micronized SS. The PG matched well to that of Ventolin® but the SP, i.e. Damax, Dmin and area were slightly smaller which can be rectified by modifying the actuator. Two novel valves showed a lower leak rate compared to the generic one used in the current propellent. The formulation containing 2% ethanol had a higher moisture content. No impurities were detected and SS assay values were close to the input. The formulations are being evaluated for stability.