Effect of Electrolytes on Octanol‐Water Partition Coefficients: Calculations with COSMO‐RS

Abstract

In this work, the possibility of the a priori predictive model COSMO‐RS to describe partitioning of pharmaceutically active compounds in the octanol‐water system (P_OW) in the presence of electrolytes is investigated. It is shown that the calculated values of P_OW depend on the pH and the ionic strength of the solution for both dissociated and non‐dissociated solutes. Whereas the partitioning of the non‐dissociated form in the presence of salts or buffers can be explicitly described by COSMO‐RS, the partitioning of the ionized pharmaceuticals is taken into account by their dissociation constants. Overall, reasonable agreement with experimental values is achieved. Principally, these types of calculations can be extended to other two‐phase systems used for extraction and formulations of pharmaceuticals and further organic solutes.