Beclomethasone dipropionate Transport and Metabolism in EpiAirway^TM Cell Layers

Precious Akhuemokhan, Chris Grainger & Ben Forbes

Institute of Pharmaceutical Science, King’s College London, SE1 9NH, UK

Summary

The biopharmaceutics of BDP has been evaluated previously by studying drug transport and metabolism across air-interfaced epithelial cell layers formed by the human airway cell line Calu-3 ^[1]. The influence of orally inhaled drug product characteristics has been demonstrated by observing differences in epithelial transport and metabolism after the application of aerosols from non-bioequivalent solution metered dose inhalers, QVAR  and Sanasthmax, which differ in formulation composition and particle size of the aerosols they generate.  In this study, experiments performed in the continuous Calu-3 cell line were replicated using primary human epithelial cells EpiAirway^TM with the aim of determining whether similar results are obtained quantitatively and qualitatively in a cell model more representative of the lung epithelium in vivo. Using the EpiAirway^TM model, absorptive transport of BDP was faster when delivered by QVAR versus Sanasthmax and the accumulation of metabolite in the receiver chamber was greater.  Clear quantitative differences were apparent between data derived from EpiAirway^TM layers compared to Calu-3 layers, with transcellular flux of BDP transport approximately 2-fold higher and metabolism to 17-BMP increased by 5 to 10-fold.  One impact of the greater metabolic capability of the primary cells in contrast to Calu-3 cells is that the amount of metabolite in the receiver well of the diffusion chamber exceeded that of the parent drug when EpiAirway^TM was used. These observations demonstrate differences that will need to be considered when designing future transport and metabolism studies, investigating the role of the formulation excipient glycerol in BDP disposition when delivered by QVAR versus Sanasthmax.