Christian Jede, Laura J. Henze, Kirstin Meiners, Malte Bogdahn, Marcel Wedel, Valeria van Axel

• A variety of in vitro dissolution and gastrointestinal transfer models have been developed aiming to predict drug supersaturation and precipitation. Further, biphasic, one-vessel in vitro systems are increasingly applied to simulate drug absorption in vitro. However, to date, there is a lack of combining the two approaches. Therefore, the first aim of this study was to develop a dissolution-transfer-partitioning system (DTPS) and, secondly, to assess its biopredictive power. In the DTPS, simulated gastric and intestinal dissolution vessels areA variety of in vitro dissolution and gastrointestinal transfer models have been developed aiming to predict drug supersaturation and precipitation. Further, biphasic, one-vessel in vitro systems are increasingly applied to simulate drug absorption in vitro. However, to date, there is a lack of combining the two approaches. Therefore, the first aim of this study was to develop a dissolution-transfer-partitioning system (DTPS) and, secondly, to assess its biopredictive power. In the DTPS, simulated gastric and intestinal dissolution vessels are connected via a peristaltic pump. An organic layer is added on top of the intestinal phase, serving as an absorptive compartment. The predictive power of the novel DTPS was assessed to a classical USP II transfer model using a BCS class II weak base with poor aqueous solubility, MSC-A. The classical USP II transfer model overestimated simulated intestinal drug precipitation, especially at higher doses. By applying the DTPS, a clearly improved estimation of drug supersaturation and precipitation and an accurate prediction of the in vivo dose linearity of MSC-A were observed. The DTPS provides a useful tool taking both dissolution and absorption into account. This advanced in vitro tool offers the advantage of streamlining the development process of challenging compounds.…