Protolytic Equilibria of Cetirizine in the Presence of Micelle-Forming Surfactants

The acid–base equilibria of cetirizine were investigated with and without the presence of differently charged micelle-forming surfactants (anionic, cationic, nonionic). The pKa values were potentiometrically determined at 25 °C and at a constant ionic strength (0.1 M NaCl). Experimental data were analyzed by applying the computer program Hyperquad 5.2.15. Based on a shift in the ionization constants (∆pKa) in micellar solutions against the pKa values determined in “pure” water under the same conditions, the effects of micelles on the protolytic equilibria of cetirizine were estimated. Applied micelles caused a shift in the protolytic equilibria of all cetirizine ionizable centers, with the piperazine function connected to aliphatic side moiety (∆pKa1 from −0.47 to +1.42), carboxyl group (∆pKa2 from −0.92 to +2.02), and piperazine nitrogen connected to phenyl rings (∆pKa3 from −2.01 to +2.19). Anionic SDS and nonionic Brij 35 micelles caused an increase in the pKa values of the ionizable centers of cetirizine, while a decrease in the pKa values was detected under the influence of cationic CTAB and nonionic TX-100 micelles. The change in the ionization pattern by micelles at pH values with biopharmaceutical significance provides indications of possible interactions of cetirizine with biomolecules of different charge and polarity under physiological conditions.