TY  - JOUR
A1  - Jede, Christian
A1  - Henze, Laura J.
A1  - Meiners, Kirstin
A1  - Bogdahn, Malte
A1  - Wedel, Marcel
A1  - van Axel, Valeria
T1  - Development and application of a dissolution-transfer-partitioning system (DTPS) for biopharmaceutical drug characterization
JF  - Pharmaceutics
N2  - 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 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.
KW  - in vitro dissolution testing
KW  - in vitro dissolution methods
KW  - in vivo dissolution
KW  - oral drug absorption
KW  - oral bioavailability
KW  - gastrointestinal
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311149
SN  - 1999-4923
VL  - 15
IS  - 4
ER  -