Passive transport properties of drug molecules are of utmost importance for their pharmacological and biopharmaceutical effectiveness. Diffusion in different media and through lipid bilayers is in many cases the ratedetermining step for the distribution in the body. In the present review an attempt is made to demonstrate the importance of solvation of drug molecules for the diffusion and partition / distribution in phases of different lipophilicity. Different approaches known in the literature to describe solvation of compounds with flexible conformation are discussed as well as the experimental methods to directly measure the energy of solvation. NSAIDs are chosen as an example of a class of drugs of different molecular structures that have already been studied thoroughly in many aspects, and a set of aliphatic alcohols can be used as a model for compartments of different lipophilic / hydrophilic properties. Thermodynamic characteristics of solvation of the drug molecules yielded by independent classical experimental methods (Gibbs energy, enthalpic and entropic terms of Gibbs energy) are studied in order to better understand diffusion and distribution properties. Correlations between in-vitro-data (partition coefficient, enthalpy of solvation) with biopharmaceutically relevant characteristics (plasma half-life) are also discussed.
Keywords: nsaid, sublimation, solvation, isothermal calorimetry, plasma half-life, solubility, passive transport, partitioning
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