Characterisation of Drug Delivery in a Pressurised Metered-dose Inhaler

Poster presentation: The anticipated phasing out of hydrofluoroalkane (HFA) propellants in pressurised metered-dose inhalers (pMDI) is motivated by the need for a more sustainable solution with a smaller equivalent carbon (CO2e) footprint. In the UK, inhalers are estimated to contribute to 3.9% of the total carbon footprint of the National Health Service; estimates range from 17 to 439 kg CO2e per patient depending upon drug type [1, 2]. The search for low Global Warming Potential (GWP) ‘green’ alternatives (at a lower cost) is principally governed by the requirement for an efficient and reliable method of drug administration, suitable for a wide range of patients with asthma and chronic obstructive pulmonary disease (COPD). The efficacy of drug delivery is dependent upon the particle size distribution and the flow required to disperse and augment the transport of the drug to the required locations in the lungs. These processes are influenced by the formulation (drug and excipients), drug and propellant mixture properties, the mechanical design of the device and the method of flow generation and particle delivery, as well as patient practice and perception. Fundamental knowledge of the particle size distribution of the dispersed phase following flash atomisation of the carrier phase is critical in controlling the prescribed dose, which can be as low as 10-15% in practice. Computational Fluid Dynamics (CFD) modelling techniques are routinely used in the design phase of new devices to study the efficacy in drug delivery [3], where generally particle size is determined from mean data collected in-vitro from staged Impactor devices. In the present work in progress, experimental data required for model validation were collected directly within the spray plume atomised in a commercially available Ventolin inhaler with propellent, HFA134a. A repeatable spray event was initiated using a piston plunger and programable linear actuator. Observations of the characteristics of the evolution of the evaporating spray plume, larger droplets and ligament structures were recorded using high-speed microscopic imaging with LED backlit illumination (with minimum resolution of 4.6 μm/pixel, field of view of 2.23 × 5.95 mm2 and frame rates greater than 5 kHz). Phase Doppler Anemometry was used to measure the particle size and axial and radial velocity distributions at a series of grid points in the jet at the nozzle exit (modified inhaler) and further from the nozzle, at a distance representative of the start of the mouth-throat (MT) region. For comparison, the particle size distribution was evaluated using a 6-stage, pharmaceutical Cascade Impactor. The complementary experimental results relating to the atomisation and particle generation processes were used to develop statistical distributions for particle size and velocities, with a view to providing data for the optimisation of modelling approaches that inform future inhaler designs and drug formulations.