Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35

Abstract

The acid–base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and ramipril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The p K a values were potentiometrically determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the computer program Hyperquad. On the basis of the shift in the p K a values (Δp K a ) determined in micellar media in relation to the p K a values previously determined in “pure” water, the effect of Brij 35 micelles on ACEIs ionization was estimated. The presence of nonionic Brij 35 micelles caused a shift in the p K a values of all ionizable groups of the investigated ACEIs (Δp K a from − 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4–8, which includes biopharmaceutically important pH values. Graphical abstract