Analytical and Bioanalytical Chemistry

, Volume 409, Issue 27, pp 6451–6462 | Cite as

Thermodynamics and molecular insight in guest–host complexes of fluoroquinolones with β-cyclodextrin derivatives, as revealed by ATR-FTIR spectroscopy and molecular modeling experiments

  • Irina M. Le-Deygen
  • Anna A. Skuredina
  • Igor V. Uporov
  • Elena V. Kudryashova
Research Paper

Abstract

β-Сyclodextrin (CD) is a perspective class of excipients used in pharmaceutical formulations to enhance solubility, bioavailability, and pharmacokinetics of various poorly soluble drugs, forming a non-covalent guest–host complex. However, the development of such formulations is usually a very laborious and time-consuming process due to lack of appropriate analytical tools to directly track and study the detailed molecular mechanism of such complex formation. Here, using guest–host complexes of fluoroquinolones (FQ) with CDs, as an example, we demonstrate the utility of ATR-FTIR to determine the thermodynamic stability, as well as structural features associated with complex formation, including involvement of certain functional groups. Furthermore, varying the CD’s side groups, we were able to tailor the CD’s geometry and binding surface to make FQ–CD interactions strong enough to potentially affect its pharmacokinetics and justify development of a new sustained-release drug formulation (dissociation constant decreased from 5 * 10−3 M to 10−5 M). 3D molecular modeling with energy optimization supports the findings and conclusions made on the basis of ATR-FTIR data analysis and explains the observed difference in dissociation constants.

Keywords

Fluoroquinolones β-Cyclodextrin Guest–host complexes ATR-FTIR spectroscopy 

Abbreviations

CD

Cyclodextrin

FQ

Fluoroquinolones

HPCD

2-Hydroxipropyl-β-cyclodextrin

LF

Levofloxacin

MCD

Methyl-β-cyclodextrin

MF

Moxifloxacin

SBECD

Sulphobutyl ether β-cyclodextrin

TB

Tuberculosis

Notes

Acknowledgments

This research is supported by RSF 15-13-00063. The authors thank Dr. Vinogradov A.A. for his comments on an earlier version of the manuscript and fruitful discussions and Dr. Putilin S.N. (Bruker AXS GmbH) for the help in X-ray experiments.

Author contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2017_590_MOESM1_ESM.pdf (160 kb)
ESM 1 (PDF 159 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of ChemistryLomonosov Moscow State UniversityMoscowRussia

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