Advanced In Silico Modeling of the Performance of Inhalation Products

Sharareh Salar-Behzadi, Shengqian Wu, Claudia Meindl, Sandra Stranzinger, Annalisa Mercuri, Stephan Mohr, Massimo Bresciani, Johannes Khinast, Eleonore Fröhlich

In vivo Cmax values and pulmonary absorption of budesonide delivered by Turbuhaler® were predicted with GastroPlusTM software, using either default pulmonary permeability data or in vitro experimental one. The experimental permeability data were gained using Calu-3 cells cultured on polycarbonate membranes (transwells) in submersion (SC) or under air-liquid interface (AIC) conditions to produce mucin. Calu-3 cells in AIC showed lower transepithelial electrical resistance (TEER) and higher permeability to budesonide than cells in SC. The produced mucin in AIC cell cultures did not reduce the transport rate of budesonide.
The experimental permeability data were lower than the calculated pulmonary permeability values predicted by the software. The software was able to predict in vivo performance reasonably well and the use of experimental permeability data further improved this prediction.
This work shows the supportive impact of combining advanced in vitro and in silico methods on the efficient modeling of pharmaceutical products in vivo performance. Development of such strong tools is the requirement for promoting safe and fast drug development.

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