Summary

Purpose: Formulation work is crucial in the development process of new drugs for inhalation. A full understanding of how the formulation, with its excipients, behaves in vivo and impacts the bioavailability of a drug candidate is important. Both in vitro and in vivo characterization are vital activities to gain this knowledge. Methods: In this study a physiologically based biopharmaceutical prediction tool for inhaled products called Lung-Sim was used to predict systemic exposure of two different formulations of beclomethasone dipropionate (with or without glycerol) when administered to rats. Before exploring whether the dissolution-retarding effects of glycerol observed in vitro translate to pharmacokinetic differences in an in vivo setting, the Lung-Sim simulations were conducted to help design the study to optimize the read out. Lung-Sim was informed of the general physiochemical properties of BDP as well as the formulation specific properties. Results: The predictions indicated that early time samplings were critical to be able to capture the impact of glycerol on BDP pharmacokinetics. Data from a small in vivo pilot study concorded with these findings. Conclusion: In silico models, such as Lung-Sim, are powerful research tools supporting the drug development of inhaled medicines. As a complement to traditional in vitro and in vivo characterization, the physiologically based biopharmaceutical prediction tools expand the drug development tool box and can save time, money and reduce the use of laboratory animals.

Key Message

In silico mechanistic modelling can be a helpful tool in the design of in vivo studies to optimize the read out when exploring new candidate drugs, formulations and devices. Through prediction-informed tailoring of the studies, the costs, the time and the number of experimental animals can be reduced.