The Thermodynamic Dissociation Constants of Clotrimazole, Terbinafine HCL, Acetylsalicylic Acid, Salicylic Acid, and Galanthamine by the Nonlinear Regression of Multiwavelength Spectrophotometric pH-Titration Data

Abstract

The mixed dissociation constants of five drugs—clotrimazole, terbinafine HCl, acetylsalicylic acid, salicylic acid, and galanthamine—at various ionic strengths I and at temperatures of 25 ° C and 37 ° C were determined with the use of multiwavelength and multivariate treatments of spectral data SPECFIT/32 nonlinear regression analysis and INDICES factor analysis. The factor analysis in the INDICES program predicts the number of components, when the data quality is high and the instrumental error is known. The thermodynamic dissociation constant p K a T was estimated by nonlinear regression of { p K a , I } data at 25 ° C and 37 ° C: for clotrimazole p K a , 1 T = 4.38(1) and 4.16(3); for terbinafine HCl p K a , 1 T = 4.19(3) and 4.12(5); for acetylsalicylic acid p K a , 1 T = 3.49(25) and 3.41(15); for salicylic acid p K a , 1 T = 3.01(1) and 3.00(1) and for galanthamine p K a , 1 T = 8.21(1) and 7.99(2) where in brackets the standard deviation is in the last significant digits. Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates found to be proven. Pharma Algorithms predicts p K a being based on the structural formulae of drug compounds.