The Effect of Ethanol Concentration on pMDI Evaporation Fraction
Linda Liao1, Ameet Sule2, Ben Okorodudu1, Ian Flaherty1, Heli Chauhan1, Andrew Newman2, Sunita Sule2, Richard Turner2. Poster presented at Digital RDD 2020; 2020 April 26 – 30; Digital Conference.
1Proveris® Scientific Corporation, Hudson, Massachusetts, USA
2H&T Presspart, Blackburn, Lancashire, UK
BACKGROUND: For aerosol drug products, traditional in vitro methods often show little correlation with in vivo performance in clinical studies, which tend to be costly and time intensive. In 2012, US FDA started the Generic Drug User Fee Amendments (GDUFA) program, aiming to expedite the delivery of safe and effective generic drugs to the public and improve upon the predictability of the review process.1 In the interim, numerous product-specific guidances were released for orally inhaled and nasal drug products (OINDPs). In May 2019, FDA released a product-specific guidance for beclomethasone dipropionate delivered by MDI that proposed approaches using new, alternative in vitro characterization studies that were more representative and/or predictive of the clinical effect in the deep lung. Measurement of the evaporation rate of the aerosol is among the recommended alternative approaches.
Due to the mechanism of aerosolization of pMDI products, aerodynamic properties—such as evaporation rate—impact drug delivery and lung deposition. However, it is extremely difficult to capture the variable bulk mass of aerosols without interrupting the spray, and limited studies regarding the evaporation rate have been reported.
In this study, we extended the basics of the well-established SprayVIEW technique (which produces calibrated, time-synchronized image sequences of the entire aerosol spray and duration) with a novel measurement method to quantify the evaporation fraction (as a measure of the evaporation rate) from non-commercial pMDI product samples across 3 different ethanol concentrations.