Stability Evaluations of Salbutamol Sulphate Propellant-Dispersible Tablets (Respitab™) for Formulation with HFA-152a.
Simon Warren1, Chen Zheng1, Sylwia Fowler1, Aneta Obirek1, Rachael Kay2 & Cuong Tran3
1i2c Pharmaceutical Services, Cardiff Medicentre, Cardiff CF14 4UJ. UK, current affiliation 2PCI Pharma Services, 3Nanopharm Ltd.
Summary
Respitab™ is a novel approach for manufacturing pressurised metered dose inhalers (pMDIs) using propellant-dispersible tablets. In this production process a tablet is dispensed into the canister, the metering valve crimped and the propellant pressure filled. This innovation circumvents manufacturing challenges associated with flammable gasses e.g. hydrofluoroalkane 152a (HFA-152a) by reducing the number of essential operator interventions associated with production and cleaning during traditional single-stage or two-stage filling. Dispensing propellant-dispersible tablets into canisters and crimping valves, independently of gassing provides greater flexibility in the manufacturing process. For example, active pharmaceutical ingredient (API) handling can be performed separately from propellant filling which as a consequence may be greatly simplified enabling significant savings in terms of investment in manufacturing equipment and modification of production facilities.
In this study Respitab propellant-dispersible tablets containing salbutamol sulphate (SS) were dispensed into plain aluminium canisters and metering valves were crimped to seal. Canisters were subjected to accelerated stability conditions (up to 3 months at 40°C / 75% RH, no foil overwrap) prior to addition of HFA-152a. Following gassing, aerosol characteristics i.e. fine particle fraction (FPF) and dose content uniformity (DCU) through canister life were determined. The moisture level within the formulation was also assessed.
FPF and DCU data were consistent over 3 months’ storage. DCU showed the mean metered dose was within acceptable limits i.e. all within ±35% of target and 90% of results within ±25% of target. FPF indicated consistent and efficient aerosol generation, with mean FPF values ranging from 62% to 66%.