Physicochemical properties of inclusion complexes of highly soluble β-cyclodextrins with highly hydrophobic testosterone propionate

Hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CyD) were used to generate
hydrophilic complexes of the poorly water-soluble drug testosterone propionate (TP). The inclusion
complexes were obtained by freeze-drying, and then analyzed at both liquid and solid states. Phase solubility
studies, performed according to the type-AL solubility diagrams of TP in presence of both CyDs, suggested the
formation of water-soluble complexes at 1:1 molar ratio. These results were confirmed by continuous variation
method (Job’s plot). Both CyDs increased water-solubility of TP 100-fold as compared to the native drug. The
host-guest arrangement of CyD complexes in a water solution was further investigated by one- and two-dimensional
NMR spectroscopy, highlighting the insertion of the tetracyclic ring of TP into the CyD cavity, and the
interaction of the pending ester chain of drug with the primary hydroxyl groups of CyDs at the narrow end of the
toroid structure. In solid phase, FTIR-ATR spectroscopy showed that the C]O stretching mode of the TP vibrational
spectrum changed if the complex between the drug and CyDs occurred. This change is temperaturedependent,
and its evolution, accounted for by deconvolution procedures, provided the thermodynamic parameters
explaining the mechanisms involved in the formation of inclusion complexes.