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Thermodynamic study of sublimation, solubility, solvation, and distribution processes of atenolol and pindolol.

Temperature dependency of saturated vapor pressure, thermochemical, and thermodynamic characteristics of sublimation, as well as fusion and vaporization processes, for atenolol and pindolol was studied. Specific and nonspecific energetic terms in the crystal lattices were estimated. Temperature dependencies of solubility in buffer (pH 7.4), in n-octanol, and in n-hexane were measured. Thermodynamic functions of solubility, solvation, and transfer processes were deduced. It was found that transfer processes for the drugs moving from water into n-octanol are determined mainly by the entropy term. Distribution coefficients of the compounds in the water/n-octanol system were derived and compared with analogous coefficients calculated from saturation solubility data in the individual solvents. The impact of mutual dissolution of water and n-octanol molecules in the water/n-octanol system on distribution coefficients is discussed.