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INTRODUCTIONUnderstanding the mechanism of passive transport is one of the most important issues in the design of new drugs. Since penetration of drugs through biological barriers is in many cases a major prerequisite for the biological effect, numerous attempts have been made to describe this process adequately. To cover the variability in biophysical characteristics of different membrane types, a set of 4 solvent systems has been used, sometimes called the "critical quartet" 1 : octanol-water (amphiphilic, aprotic solvent); propylenglycoldipelargonatwater (hydrogen bond acceptor); chloroform-water (hydrogen bond donor); and cyclohexane-water (purely hydrophobic).Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, ǻ , as well as the entropies of sublimation, ǻ , and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, ǻ , and the transfer Gibbs energy from water to octanol, ǻ . Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropycompensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed. ). This demonstrates once more that differently sized aggregates (subunits) take part in the elementary steps of diffusion, and that these subunits determine the diffusion mechanism (activation volume, activation thermodynamic parameters of the diffusion, and so on).

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