In a recent FDA guidance document[[i]], characterization of the emitted aerosol spray velocity profiles (spray velocity) was proposed as an alternative approach to comparative clinical endpoint bioequivalence (BE) studies. The spray velocity has been reported as an important parameter for drug-device combination products such as pMDIs and SMIs[[ii]]. This paper describes a clear methodology for measuring the spray velocity with the leading edge of the plume and presents results from four (4) US approved inhalation products. In this study, we extended the well-established SprayVIEW® technique for providing time-synchronized plume characterization in a novel way to determine the spray velocity from pMDI and SMI test samples available in the USA.
The test products were selected to demonstrate the new measurement methodology and investigate the effects of product type (pMDI/SMI), propellant type (HFA-134a/HFA-227a), formulation type (suspension/solution) and number of excipients on the performance. General conclusions are as follows for the products tested: 1) the emitted aerosol spray velocity from the SMI (average of 1.55 m/s) was significantly lower than all of the pMDI products (average of 4.31 – 9.47 m/s); 2) pMDIs with HFA-227a propellant had higher spray velocities (average of 9.47 m/s) compared to those with HFA-134a propellant (average of 4.31 m/s and 5.41 m/s respectively); 3) Products with higher spray velocity have shorter spray durations, which is another parameter that could affect the pulmonary delivery efficiency; and 4) the formulation type and number of excipients had minimal effects on the spray velocity.
A novel characterization method for determining the emitted aerosol velocity profiles from pMDI and SMI products was introduced with sufficient sensitivity to distinguish between different types of products, propellants and formulations.