Association models for an amphiphilic drug in aqueous solutions of high ionic strength from calorimetric studies

Abstract

Theoretical treatments are presented to describe enthalpy changes in solutions of amphiphilic compounds in which primary micelles are formed by continuous association processes below the critical micelle concentration (c.m.c.) and subsequently grow with increase of concentration by the stepwise addition of monomers. The models have been applied to data obtained by heat conduction calorimetry for the association of the amphiphilic phenothiazine drug, promethazine hydrochloride, in the presence of 0.6 mol dm −3 NaCl. The most satisfactory simulation of data was obtained using association models in which a limited association was assumed below the c.m.c. leading to the formation of either trimers (by a cooperative association process) or tetramers (by stepwise association with equilibrium constants of equal magnitude). Subsequent growth of these primary aggregates with increase of concentration in the post-c.m.c. region was by the stepwise addition of monomers according to a cooperative association scheme. The models have permitted the evaluation of molar enthalpy changes and equilibrium constants for the formation and growth of the primary micelles.