Membrane-water partitioning – tackling the challenges of poorly soluble drugs using chaotropic co-solvents

Abstract: Many newly developed drugs suffer from poor water solubility and low bioavailability and hence, need special formulation vehicles like vesicular or micellar drug delivery systems. The knowledge of their membrane-water partition coefficient K becomes critical as is governs drug loading and release from the vehicle, as well as absorption into the body. The dilemma is that measuring K is particularly challenging for these very compounds. Here we establish a strategy to resolve this problem. We added DMSO to shift K and solubility into a convenient range and extrapolated these results back to zero-DMSO. Isothermal titration calorimetry revealed that logK of the kinase inhibitor Lapatinib decreased proportionally to DMSO content (2.5 – 20v%) with a slope of −1/20v% (m value = 28 kJ/mol). This implies a K of 84 mM−1 in DMSO-free buffer. This strategy should be transferable to other poorly soluble drugs and further detection methods

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Biophysical chemistry. - 277 (2021) , 106654, ISSN: 0301-4622

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2021
• Creator: Naßwetter, Leonie C. ; Fischer, Markus ; Scheidt, Holger ; Heerklotz, Heiko

Further information

• DOI: 10.1016/j.bpc.2021.106654
• URN: urn:nbn:de:bsz:25-freidok-2230029
• Rights: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:30 AM CEST