In Vitro – Ex Vivo Correlation of Fluticasone Propionate Pharmacokinetic Profiles

Maria Börjel, Ewa Selg, Per Gerde

Background: Today there are no available in vitro methods predicting the in vivo pharmacokinetics of inhalation drugs in development. Such methods are needed in both the pharma industry and in academic research. The aim of this work was to compare pharmacokinetic data generated by the promising in vitro dissolution/absorption method DissolvIt® and the ex vivo isolated perfused and ventilated lung of the rat (IPL), which is a well- established experimental model for studying lung pharmacokinetics.
Methods: The PreciseInhale® aerosol system was used to generate and dispense respirable powder aerosols of two formulations containing fluticasone propionate (FP): Flixotide and Flutiform, in pMDI canisters. Aerosols from identically actuated inhalers were either deposited on the small circular cover slip glasses used in DissolvIt® or precisely dosed to the IPL perfused in single-pass mode. Analytical quantitation of FP in the samples was performed by LC/MS/MS.
Results: The slight differences in pharmacokinetic profiles of FP in the two pMDI formulations were similarly detected both in the DissolvIt® and IPL systems.
Conclusions: By generating in vivo-like pharmacokinetic profiles with Cmax and tmax, DissolvIt® may provide a useful tool for predicting the in vivo pharmacokinetic behavior of different inhalation formulations in development, and be a valuable in vitro dissolution/absorption method for in vitro – in vivo correlation (IV-IVC).

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