Wiktoria Wegrzyn1,Rachael Kay & Cuong Hoa Tran
1i2c Pharmaceutical Services, Cardiff Medicentre, Cardiff. CF14 4UJ. UK.
Summary
Introduction The current drive to produce the next generation pressurised metered dose inhalers (pMDIs) using low global warming potential (GWP) propellants presents ongoing challenges for the pharma industry. Respitab® is a propellant dispersible tablet technology, consisting of one or more jet-milled micronized active pharmaceutical ingredients (APIs) and approved inhalation excipients e.g. lactose and menthol. It is designed to overcome manufacturing challenges such as drug loss and suspension inhomogeneity, and offers flexibility in separating drug dispensing from propellant filling, which will provide advantages when utilising flammable propellants. Propellant dispersible tablets provide consistent delivered dose and efficient aerosol properties.
Research Hypothesis To investigate the application of Respitab pMDI technology to formulate a salmeterol xinafoate (SX) & fluticasone propionate (FP) combination pMDI using the low-GWP propellant HFC 152a.
Methods SX/FP combination product was prepared with menthol and lactose (Lac) and dispensed into plain aluminium 14 ml canisters. After crimping with metering valves, propellant HFC 152a was pressured filled into the canisters. Standard pharmacopoeial tests were conducted to determine delivered dose uniformity and aerodynamic particle size distribution (APSD).
Results and Discussion SX/FP pMDI containing HFC 152a produced high fine particle fraction (FPF, %<5.0 µm) values and uniform delivered dose throughout product life. This development formulation was non-optimised in terms of API particle size, and excipient properties. Nevertheless, APSD profiles compared favourably with a marketed reference product i.e. Seretide.
Conclusion Respitab SX/FP pMDI produces a consistent, uniform and high quality aerosol utilising the next generation low-GWP propellant HFC 152a.
Key Message
Respitab SX/FP combination pMDI exemplifies a novel approach to pMDI manufacture, reducing the challenges and complexities of using HFC 152a, while producing high performance pMDIs. The use of a propellant dispersible tablet enables flexible manufacturing and separation of drug dispensing from propellant filling, a significant advantage when using flammable propellants.