The Effects of Anionic, Cationic, and Nonionic Surfactants on Acid-Base Equilibria of ACE Inhibitors

The pK(a) values of ACE inhibitors captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, and zofenopril were determined by potentiometry. Because to the presence of single or several ionizable groups (carboxyl, thiol, primary and secondary amino groups) these substances represent acids and ampholytes. Determinations of pK(a) values were performed at 25 degrees C and constant ionic strength of 0.1 M (NaCl), in the absence and in the presence of surfactants, anionic sodium dodecyl sulfate (SDS), cationic cetyltrimethyl ammonium bromide (CTAB), and nonionic 4-octylphenol polyethoxylate (TX 100). A computer program Hyperquad was used to derive pK(a) values from the data obtained by potentiometric titrations. The observed shift of pK(a) values from +1.90 to -1.54 pK units demonstrated a significant effect of the surfactants on ionization of ACE inhibitors. It has been observed that the carboxyl group was more susceptible to the effect of the above surfactants than the amino group. Also, among the three surfactants employed, SDS expressed the most prominent effect on acidbase equilibria. On the basis of the shifts of pK(a) values in the presence of the applied surfactants different ACE inhibitormicelle interactions were suggested.