Intestinal solubility and absorption of poorly water soluble compounds: predictions, challenges and solutions

Therapeutic Delivery
Jonas H Fagerberg, Christel As Bergström

Abstract

We have explored for which type of compounds biorelevant dissolution profiling in simulated intestinal fluids would accurately predict solubility in human intestinal fluid. In total, 474 solubility values in simulated and aspirated human intestinal fluid for 78 drugs were compiled and analyzed. Significant solubilization in the colloidal structures was obtained in fasted and fed state fluids for drug compounds with a logD(oct)>3. Highly lipophilic compounds with high melting points (Tm > 200 °C) could also be significantly solubilized, but typically such compounds had solubility values in the lower µg/ml range also in the presence of the colloidal structures. On the basis of our analysis, compounds with a logD(oct)>3 should be explored in biorelevant dissolution media to better predict in vivo performance after oral dosing.

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Citations

Mar 2, 2016·Advanced Drug Delivery Reviews·Christel A S BergströmChristopher J H Porter
Sep 1, 2016·Molecular Pharmaceutics·Danny RiethorstPatrick Augustijns
Jun 22, 2017·International Journal of Pharmaceutics·Toshiyuki NiwaKeita Kondo
Jan 29, 2020·The AAPS Journal·Deanna M MudieChristel A S Bergström
Mar 11, 2020·International Journal of Pharmaceutics: X·Deanna M MudieDavid T Vodak
Mar 2, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Harriet Bennett-LenaneBrendan T Griffin
Apr 20, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·D DahlgrenH Lennernäs
Dec 10, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Michael HolmboeChristel A S Bergström
Nov 2, 2017·The Journal of Physical Chemistry. B·Andrew J ClulowBen J Boyd
Oct 2, 2021·AAPS PharmSciTech·Gayathri Ramachandran, M S Sudheesh

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Methods Mentioned

BETA
profiler

Software Mentioned

OrBiTo
FaSSIF
GATS4s
FeSSIF
ADMET Predictor

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