The thermodynamic dissociation constants of ambroxol, antazoline, naphazoline, oxymetazoline and ranitidine by the regression analysis of spectrophotometric data

The mixed dissociation constants of five drug acids—ambroxol, antazoline, naphazoline, oxymetazoline and ranitidine—at various ionic strengths I of range 0.01 and 1.0 and at temperatures of 25 and 37 °C were determined using SQUAD(84) regression analysis of the pH-spectrophotometric titration data. A proposed strategy of efficient experimentation in a protonation constants determination, followed by a computational strategy for the chemical model with a protonation constants determination, is presented on the protonation equilibria of ambroxol. The thermodynamic dissociation constant <F>pKaT</F> was estimated by non-linear regression of {pKa, I} data at 25 and 37 °C: for ambroxol <F>pKa,1T=8.05 (6)</F> and 8.25 (4), log <F>β21T=11.67 (6)</F> and 11.83 (8), for antazoline <F>pKa,1T=7.79 (2)</F> and 7.83 (6), <F>pKa,2T=9.74 (3)</F> and 9.55 (2), for naphazoline <F>pKa,1T=10.81 (1)</F> and 10.63 (1), for oxymethazoline <F>pKa,1T=10.62 (2)</F> and 10.77 (7), <F>pKa,2T=12.03(3)</F> and 11.82 (4) and for ranitidine <F>pKa,1T=1.89 (1)</F> and 1.77 (1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found. [Copyright &y& Elsevier]