ISBN 9783843957120

978-3-8439-5712-0, Reihe Thermodynamik

Christopher Espen Fritschka
Influence of pH and Electrolytes on Solubility and Partitioning of Pharmaceuticals

142 Seiten, Dissertation Technische Universität Dortmund (2026), Softcover, A5

Zusammenfassung / Abstract

This thesis presents a robust framework based on the ePC-SAFT equation of state that unifies the description of ionization for weak acids and bases using thermodynamically consistent quantities. Using thermodynamic activities allowed a straightforward integration of external influences of pH and various electrolytes on ionization. This was essential for an accurate description of solubility and distribution.

The solubility of pharmaceutical compounds in water could be quantitatively predicted with this model as a function of pH and electrolytes. Additionally, the formation of API salts was seamlessly incorporated, representing a significant advancement in predicting API solubilities in biorelevant media.

A second key focus of this thesis was developing a reproducible method for determining distribution and partition coefficients of dissolved ionizable substances between an organic and an aqueous phase. The proposed approach was robust and delivered reproducible results even under the influence of electrolytes and across various organic solvents.

Additionally, distribution and partition coefficients of ionizable APIs could be qualitatively and even quantitatively predicted with the developed framework in ePC SAFT.