%0 Journal Article
%T Combined in Vitro-in Silico Approach to Predict Deposition and Pharmacokinetics of Budesonide Dry Powder Inhalers.
%A Ruzycki CA
%A Murphy B
%A Nathoo H
%A Finlay WH
%A Martin AR
%J Pharm Res
%V 37
%N 10
%D Sep 2020 29
%M 32995953
%F 4.58
%R 10.1007/s11095-020-02924-7
%X <B>OBJECTIVE: </B>A combined in vitro - in silico methodology was designed to estimate pharmacokinetics of budesonide delivered via dry powder inhaler.<BR><B>METHODS: </B>Particle size distributions from three budesonide DPIs, measured with a Next Generation Impactor and Alberta Idealized Throat, were input into a lung deposition model to predict regional deposition. Subsequent systemic exposure was estimated using a pharmacokinetic model that incorporated Nernst-Brunner dissolution in the conducting airways to predict the net influence of dissolution, mucociliary clearance, and absorption.<BR><B>RESULTS: </B>DPIs demonstrated significant in vitro differences in deposition, resulting in large differences in simulated regional deposition in the central conducting airways and the alveolar region. Similar but low deposition in the small conducting airways was observed with each DPI. Pharmacokinetic predictions showed good agreement with in vivo data from the literature. Peak systemic concentration was tied primarily to the alveolar dose, while the area under the curve was more dependent on the total lung dose. Tracheobronchial deposition was poorly correlated with pharmacokinetic data.<BR><B>CONCLUSIONS: </B>Combination of realistic in vitro experiments, lung deposition modeling, and pharmacokinetic modeling was shown to provide reasonable estimation of in vivo systemic exposure from DPIs. Such combined approaches are useful in the development of orally inhaled drug products.