The dissolution (buffer solutions pH 2.0, pH 7.4, 1-octanol and n-hexane), distribution (1-octanol/buffer pH 7.4 system, n-hexane/buffer pH 7.4 system) and permeation (buffer pH 7.4, PermeaPad barrier) of nadolol (NDL) - a beta-blocker BCS Class III drug with antianxiety potential - were studied at different temperatures. The apparent thermodynamic parameters of the outlined processes were derived from the temperature dependences of the experimental solubilities, distribution and permeability coefficients. Comparative analysis of the driving forces was used to disclosing the behavior of the compound in different biologic media. Estimation of the influence of experimental temperature on the permeability of nadolol allowed to evaluate the energy of activation and the permeability enhancement factor equaling to EF = 2.16 upon 15 °C temperature rise. A good linear correlation (R = 0.9988, F = 831.66) between the distribution and permeability coefficients has been derived and would be applied to the prediction of the permeability from the distribution at a specific temperature. Comparison of the enthalpy contributions to the transferring from buffer pH 7.4 to 1-octanol and to the permeability through the lipophilic PermeaPad barrier showed the similar trends in these two processes. The present study has the perspectives for the application in the design of the drug formulations for the complex therapy of cardiovascular and depressive-like disorders.
