Accelerated Stability Studies with pMDIs of Respitab HFA-152a Propellant Dispersible Salbutamol Tablets

Rachael Kay, Aneta Obirek, Wiktoria Wegrzyn and Cuong Tran

i2c Pharmaceutical Services, Cardiff Medicentre, Cardiff, CF14 4UJ, UK.

Summary

Transition to next-generation low global warming potential propellants for production of pressurised metered dose (pMDIs) presents challenges with process equipment and adapting manufacturing environments to ensure safe working with propellants classified as flammable.  Respitab®, with drug in tablet form dispensed directly into canisters and crimped, avoids the need for pressurised mixing vessels and manipulation of large volumes of propellant in staffed working environments.  Thus, Respitab offers a unique approach to developing formulations in Next Generation propellants such as HFA-152a.

A Respitab salbutamol sulphate (SS) dispersible tablet formulation was prepared in HFA-152a and accelerated storage stability (6 months at 40°C / 75% relative humidity) assessed.  The product was manufactured in plain aluminium canisters and stored unprotected.  Following storage, pMDI canisters were evaluated using Next Generation Impactor (NGI) aerosol characterisation.

Aerosol characterisation of SS dose content uniformity (DCU) and aerodynamic particle size distribution (APSD) showed minimal changes over 6 months storage. DCU showed metered dose of 10 canisters was within acceptable limits with all measurements within ±35% of target and 90% of results within ±25% of target. APSD showed good reproducibility between the 5 pMDIs tested. While some small but statistically significant differences in APSD patterns were observed during storage, fine particle fraction (FPF, % < 5µm) indicated efficient aerosol production, with mean FPF decreasing from 63% to 56%. In comparison with off the shelf Ventolin obtained via pharmacy wholesaler, the beginning of can life, no accelerated storage, performance of Respitab showed a mean FPF of 49% compared with 46% for Ventolin.

Key Message

A Respitab propellant-dispersible SS tablet formulation was used to prepare pMDI in plain aluminium canisters containing HFA-152a.  Samples were stored, without foil overwrap, for 6 months under accelerated stability conditions.  Key performance indicators i.e. delivered dose and fine particle fraction remained efficient throughout the storage period.