What is modulating solubility in simulated intestinal fluids?

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Giorgio OttavianiBernard Faller

Abstract

The aim of this study was to understand which parameters are responsible for the selective modulation of compounds solubility in simulated intestinal fluids. The solubility of 25 chemically diverse reference compounds was measured in simulated intestinal fluid (FaSSIF-V2) and in aqueous phosphate and maleate buffers. Electrostatic interactions between compounds and the bio-relevant medium components seem to explain the different solubility behavior observed for acids and bases. The solubility of ionized acids is not increased in FaSSIF-V2 probably due to electrostatic repulsions with the media components. Lipophilicity plays an important role but mainly for charged bases with a logP>4 (or logD(6.5)>1.9). When the aqueous solubility is mainly driven by lipophilicity, the FaSSIF-V2 components seem to improve the solubility of basic compounds to a greater extent than for compounds whose solubility is limited by crystal packing. These results suggest that ionization, lipophilicity and crystal packing play important but peculiar roles in controlling solubility in FaSSIF-V2 compared to that in aqueous buffer and this information could be useful to guide medicinal chemists and formulation scientists.

References

Feb 26, 2004·The Journal of Pharmacy and Pharmacology·Edmund S KostewiczJennifer B Dressman
Apr 22, 2004·The Journal of Pharmacy and Pharmacology·Maria VertzoniChristos Reppas
Jul 22, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christel A S BergströmPer Artursson
Sep 14, 2004·Pharmaceutical Research·Karine AndrieuxCécile Grabielle-Madelmont
Apr 2, 2005·Journal of Medicinal Chemistry·Bernard FallerXavier Briand
Mar 3, 2007·Nature Reviews. Drug Discovery·Christopher J H PorterWilliam N Charman
Jun 26, 2007·Advanced Drug Delivery Reviews·Bernard Faller, Peter Ertl
Jul 3, 2007·Advanced Drug Delivery Reviews·Jochem Alsenz, Manfred Kansy
Jan 22, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Bruno BardPierre-Alain Carrupt
Apr 12, 2008·Pharmaceutical Research·Ekarat JantratidJennifer B Dressman
Nov 11, 2008·Current Drug Metabolism·Edward H KernsGuy T Carter
Apr 18, 2009·Journal of Pharmaceutical Sciences·Joachim BrouwersPatrick Augustijns

❮ Previous
Next ❯

Citations

Oct 15, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Valentina AnutaOctavian Tudorel Olaru
Mar 2, 2016·Advanced Drug Delivery Reviews·Christel A S BergströmChristopher J H Porter
Nov 10, 2015·Journal of Medicinal Chemistry·Renier van der WesthuyzenKelly Chibale
Feb 28, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·M VogtherrC Saal
Jun 19, 2013·Journal of Pharmaceutical and Biomedical Analysis·Krisztina Takács-NovákPiroska Szabó-Révész
Nov 13, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christel A S BergströmAnette Mullertz
Oct 1, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christel A S BergströmAnders Lindahl
Sep 5, 2014·Pharmaceutical Research·Jonas H FagerbergChristel A S Bergström
Jan 29, 2020·The AAPS Journal·Deanna M MudieChristel A S Bergström
Nov 24, 2020·Chemické Zvesti·Helena D Janse van RensburgGisella Terre'Blanche
Dec 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohd SaeedMousa Alreshidi
Jul 14, 2021·Journal of Biomolecular Structure & Dynamics·Vishal K SinghRamendra K Singh
Jun 2, 2012·Molecular Pharmaceutics·Jonas H FagerbergChristel A S Bergström
Aug 17, 2018·Molecular Pharmaceutics·Johannes WiestLorenz Meinel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.

Related Papers

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Sarah ClaryssePatrick Augustijns
Journal of Medicinal Chemistry
Christel A S BergströmIna Hubatsch
© 2021 Meta ULC. All rights reserved