Transitioning pMDIs to SMIs: salbutamol as a case study
Dylan Antoniak1, Philippe Rogueda1, Adam Stuart1 & Graham Purkins1
1Merxin Ltd, 1 Innovation Drive, King’s Lynn, Norfolk, PE30 5BY, United Kingdom
Summary
There is significant potential benefit in moving from pressurised metered dose inhalers (pMDIs) to soft mist inhalers (SMIs); SMIs are easy to use, may deliver a higher dose to the deep lung and do not require propellant. This paper examines the delivery of salbutamol as a case study to demonstrate how a pMDI can be transitioned to an SMI. It compares the pMDIs Ventolin® (GSK) and Salamol® (Teva) with an SMI – MRX004 (Merxin Ltd) loaded with a commercial 5 mg/mL aqueous salbutamol nebule solution (Aliud). Aerodynamic particle size distribution (APSD) by next generation impactor (NGI), delivered dose (DD), and droplet size distribution (DSD) by laser diffraction were analysed and compared. The results show that the slower plume velocity of MRX004 compensates for its higher median mass aerodynamic diameter (MMAD) – 3.2 µm compared with 2.4 µm for Ventolin® and 2.1 µm for Salamol® – leading to MRX004 to have lower throat deposition, higher fine particle fraction (FPF) and a fine particle dose (FPD) close to that of the pMDIs, despite a much lower total DD than the pMDIs. The FPF was 63.2% for MRX004, 33.6% for Ventolin® and 40.7% for Salamol®; the DD was 56 µg for MRX004, 128 µg for Ventolin® and 108 µg for Salamol®; and the FPD was 35.1 µg for MRX004, 41.4 µg for Ventolin® and 44 µg for Salamol®. MRX004 has a much smaller metering chamber than the pMDIs. MRX004 has a significantly lower deposition in the throat than the pMDIs. When compared to the DSD results, the Dv(50) measurements were 4.7 µm, 2.1 µm and 4.1 µm for MRX004, Ventolin® and Salamol® respectively. This shows that the high-velocity spray of a pMDI in comparison to the slow mist produced by MRX004 results in impaction that reduces the efficiency of the delivery to the deeper parts of the lungs. These results suggest that MRX004, an SMI, can potentially match or better the performance of pMDIs with additional tuning of the device and formulation. This performance match linked with the lack of propellant makes an SMI option preferable for a low carbon footprint future.