A study of supramolecular host-guest interaction of dothiepin and doxepin drugs with cyclodextrin macrocycles

Inclusion complexation behavior of dothiepin (DOT) and doxepin (DOX) with two cyclodextrins (alpha-CD and beta-CD) were studied by absorption, fluorescence, time resolved fluorescence, scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transformation infrared spectroscopy (FT-IR), differential scanning colorimetry (DSC), powder X-ray diffraction (PXRD), proton nuclear magnetic resonance (H-1 NMR) and molecular modeling methods. Absorption and fluorescence spectral studies reveal that both drugs form different types of inclusion complexes with alpha-CD and beta-CD. DOT and DOX exhibit short life time in aqueous medium (DOT similar to 2.29 ns, DOX similar to 1.89 ns) and higher in CD medium (DOT:alpha-CD similar to 3.45 ns, DOT:beta-CD similar to 4.84 ns, DOX:alpha-CD similar to 3.55 ns and DOT:beta-CD similar to 4.33 ns). The supramolecular structure of the nano-sized sphere and agglomerate was established by TEM. Alkyl chain and aromatic ring protons of the drug molecule are entrapped in the CD nanocavities. The significant proton chemical shifts give evidence for expected inclusion complex formation. PM3 calculations suggest that the alkyl chain encapsulation is most energetically favored in alpha-CD. The positive free energy and entropy changes indicated that both inclusion complexation processes are non-spontaneous and entropy driven. (C) 2014 Elsevier B.V. All rights reserved.