Solubility and pKa of select pharmaceuticals in water, ethanol, and 1-octanol

Solubilities of six pharmaceuticals, namely nadolol, atenolol, bifonazole, nimesulide, estrone, mefenamic acid at constant pH, were measured over the range of temperature from (240 to 340) K in three important for drug solvents: water, ethanol, and 1-octanol using the dynamic method and spectroscopic UV-Vis method. Dissociation constants and corresponding pK(a) values of the drugs were obtained with the Bates-Schwarzenbach method using UV-Vis Perkin-Elmer Lambda 35 Spectrophotometer at temperature 298.15 K in the buffer solutions. Our experimental pK(a) values for nadolol, bifonazole, nimesulide, and mefenamic acid are 9.3, 5.85, 7.34. and 3.88, respectively. The basic thermal properties of pure drugs i.e. fusion and glass-transition temperatures, as well as the enthalpy of fusion and the molar heat capacity at the glass-transition (at constant pressure) have been measured using the differential scanning micro-calorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The experimental solubility results have been correlated by means of three commonly known G(E) equations: the Wilson, NRTL, and UNIQUAC with the assumption that the systems studied here are simple eutectic mixtures. The activity coefficients of pharmaceuticals in saturated solutions in each correlated binary mixture were calculated from the experimental results. Prediction of solubility in water at T = 298.15 K was made by the group contribution method. (C) 2010 Elsevier Ltd. All rights reserved.