Integration of gastric supersaturation and precipitation into predictive in vitro/in silico tools based on intraluminal formulation characterization in humans.

Currently, many promising drug candidates fail during costly and time-consuming clinical trials. In addition, authorized drugs often suffer from suboptimal performance in clinical practice. An important underlying reason for these mediocre scenarios is a poor prediction of drug absorption in the body based on nonclinical experiments. While the pharmaceutical industry expresses an urgent need for more predictive absorption tools, their development requires a fundamental, in-depth understanding of the underlying processes. One of the processes that may seriously compromise absorption following oral administration, but has never been characterized properly, is the precipitation of drugs in the stomach. To fill this current gap in our understanding, the present research proposal comprises a unique approach to evaluate gastric precipitation of selected model drugs in healthy volunteers. This will generate novel insights into the mechanisms of drug precipitation in vivo and its importance for drug absorption. Subsequently, these new insights will be integrated into innovative tools for the in vitro and/or computational evaluation of drug candidates, enabling the adequate prediction of the risk on gastric drug precipitation in vivo. As such, the research project will significantly contribute to an increasingly efficient drug development process leading to failure reduction in clinical trials and better performing drugs