Determination of the partition coefficients, acid dissociation constants, and intrinsic solubility of carbenoxolone.

Overview

The dissociation constants, partition coefficients, and solubility of carbenoxolone (1) were determined using tritium-labeled drug. The partition and solubility methods were used to assess the dissociation constants of carbenoxolone, while the pKa of the structurally related triterpenoid, enoxolone (2) was determined using a spectrophotometric method. The true partition coefficient (TPC) of carbenoxolone was found to be 643.8 in an n-octanol:aqueous buffer system, while its intrinsic solubility (So) was 1.63 x 10(-5) M. The apparent partition coefficient (APC) was independent of the concentration of carbenoxolone over the pH range of 3 to 7. The values of pk1 and pk2 for carbenoxolone, obtained by the partition and solubility methods, were in reasonably good agreement. The observed pKa value of enoxolone enabled the assignment of pk2 (the weaker acid grouping) to the carboxyl group at C-30.