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Equilibrium and structural characterization of ofloxacin–cyclodextrin complexation

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Abstract

The enantiomer-specific characterization of ofloxacin–cyclodextrin complexes was carried out by a set of complementary analytical techniques. The apparent stability constants of the ofloxacin enantiomers with 20 different cyclodextrins at two different pH values were determined to achieve good resolution capillary electrophoresis enantioseparation either to establish enantioselective drug analysis assay, or to interpret and design improved host–guest interactions at the molecular level. The cyclodextrins studied differed in the nature of substituents, degree of substitution (DS), charge and purity, allowing a systematic test of these properties on the complexation. The seven-membered beta-cyclodextrin and its derivatives were found to be the most suitable hosts. Highest stability and best enantioseparation were observed for the carboxymethylated-beta-cyclodextrin (DS ~ 3.5). The effect of substitution pattern (SP) was investigated by molecular modeling, verifying that SP greatly affects the complex stability. Induced circular dichroism was observed and found especially significant on carboxymethylated-beta-cyclodextrin. The complex stoichiometry and the geometry of the inclusion complexes were determined by 1H NMR spectroscopy, including 2D ROESY techniques. Irrespective of the kind of cyclodextrin, the complexation ratio was found to be 1:1. The alfa-cyclodextrin cavity can accommodate the oxazine ring only, whereas the whole tricyclic moiety can enter the beta- and gamma-cyclodextrin cavities. These equilibrium and structural information offer molecular basis for improved drug formulation.

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Acknowledgments

This work was supported by the National Scientific Research Fund of Hungary, OTKA K73804 and TÁMOP 4.2.1.B-09/1/KMR. This paper was also supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (Sz. B.).

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Semmelweis University and Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes Endre u. 9, Budapest, 1092, Hungary

    Gergő Tóth, Réka Mohácsi, Ákos Rácz, Péter Horváth, Szabolcs Béni & Béla Noszál

  2. Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy, Targu Mures, 38 Gh, 540139, Marinescu, Romania

    Aura Rusu

  3. Cyclolab Ltd., Illatos út 7, Budapest, 1097, Hungary

    Lajos Szente

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  1. Gergő Tóth
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Correspondence to Gergő Tóth.

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Tóth, G., Mohácsi, R., Rácz, Á. et al. Equilibrium and structural characterization of ofloxacin–cyclodextrin complexation. J Incl Phenom Macrocycl Chem 77, 291–300 (2013). https://doi.org/10.1007/s10847-012-0245-2

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