| Резюме: |
Low aqueous solubility is one of the major problems in oral drug delivery, as it leads to very low or highly variable oral drug bioavailability. The dissertation provides a systematic study of one of the classical approaches for drug solubility enhancement: solubilization in micellar surfactant solutions. The aims of the dissertation are to clarify how the surfactant and drug molecular structures determine the micellar solubilization capacity and to provide mechanistic physicochemical interpretation of the observed effects. Three hydrophobic drugs (progesterone, danazol and fenofibrate) were studied, as well as a wide range of surfactants (more than 20 species). It was found that (1) the solubilization of hydrophobic drugs increases linearly with the increase of the surfactant hydrophobic chain length, regardless of the charge and type of the surfactant hydrophilic head group, (2) ion-dipole interactions contribute significantly to the solubilization of steroidal drugs in ionic surfactant micelles (3) the ethoxylation of sodium dodecyl sulfate decreases drug solubilization, most likely due to more difficult packing of the molecules in the micelles and (4) fenofibrate is solubilized in the hydrophobic core of nonionic surfactant micelles and in the palisade layer of ionic surfactant micelles, as determined via UV-spectroscopy.
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