The acid–base equilibria of
rupatadine fumarate were investigated
in the absence and the presence of differently charged anionic (sodium
dodecyl sulfate), cationic (cetyltrimethylammonium bromide),
and nonionic (4-octylphenol polyethoxylate) surfactants. The pK
a values of rupatadine and fumaric acid were
potentiometrically determined at 25 °C and at a constant ionic
strength (0.1 M NaCl). The obtained potentiometric data were evaluated
with use of the computer program Hyperquad. Ionization in the surfactant-free
media was defined, and the effects of surfactants on protolytic equilibria
of rupatadine were estimated, based on a shift of the apparent ionization
constants determined in micellar solutions against the pK
a values in water. The anionic SDS micelles caused an
increase in the pK
a values of all the
rupatadine ionization centers (ΔpK
a up to +1.44), while the shift of protolytic equilibria in different
directions was observed in the case of the cationic CTAB (ΔpK
a from −1.99 to +0.14) and the nonionic
TX-100 (ΔpK
a from −0.72 to
+0.38) micelles. Distribution diagrams of the equilibrium forms as
a function of pH indicate that the change in distribution is most
strongly expressed in the pH range 4–8 which includes biopharmaceutically
important pH values.