Thermodynamics and mathematical modeling of the partitioning of chlorpromazine between n-octanol and aqueous buffer.

The distribution of chlorpromazine (CPZ) between aqueous buffer solutions and 1-octanol was studied over a wide range of pH, buffer concentration, and temperature. A mathematical model was developed to simulate the distribution profiles. It is assumed that only monomers of CPZ exist in the organic phase, whereas in the aqueous phase, association equilibria were assumed to occur. The model predicted the formation of dimers and no higher aggregates over most of the concentration range covered in this study. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Positive values of delta H and delta S were obtained for the transfer of CPZ from the aqueous to the organic phase. The process is entropy controlled indicative of a hydrophobic interaction between CPZ and the aqueous solvent.