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Isothermal titration calorimetry (ITC) study of natural cyclodextrins inclusion complexes with drugs

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Abstract

Isothermal titration calorimetry (ITC) was used to characterize inclusion complex formation of natural cyclodextrins (α- and β-cyclodextrin) with three drugs ((+)brompheniramine, (±)brompheniramine, cyclopentolate) in aqueous solutions. ITC measurements were carried out at 298.15 K on a Microcal OMEGA ultrasensitive titration calorimeter (MicroCal Inc.). The experimental data were analyzed on the basis of the model of a single set of identical sites (ITC tutorial guide). β-CD forms inclusion complexes of stoichiometry 1:1 with the all investigated drugs. In turn, smaller molecule of α-CD forms inclusion complexes of two different stoichiometry: with bigger molecules ((+)brompheniramine and (±)brompheniramine) of a stoichiometry 2:1 and with smaller molecules (cyclopentolate) of a stoichiometry 1:2. Based on the experimental values of equilibrium constant (K) and enthalpy of complex formation (ΔH), the Gibbs energy of complex formation (ΔG), and the entropy of complex formation (ΔS), have been calculated, for all the investigated systems. Obtained results showed that complex formation of β-CD (bigger molecule with wider cavity compared to β-CD) with both (+)brompheniramine, (±)brompheniramine, and cyclopentolate is enthalpy driven while complexes of α-CD with the all investigated drugs are enthalpy-entropy stabilized. This indicated that the difference in the cavity dimensions is reflecting in different driving forces of complex formation and binding modes what resulted in different stoichiometry of the obtained inclusion complexes.

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Acknowledgements

This study was partially supported by the European Union within European Regional Development Fund, through grant Innovative Economy (POIG.01.01.02-14-102/09).

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Authors and Affiliations

  1. Institute of Physical Chemistry of Polish Academy of Science, Kasprzaka44/52, 01-224, Warsaw, Poland

    Małgorzata Wszelaka-Rylik & Paweł Gierycz

  2. Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warynskiego 1, 00-645, Warsaw, Poland

    Paweł Gierycz

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  1. Małgorzata Wszelaka-Rylik
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  2. Paweł Gierycz
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Correspondence to Paweł Gierycz.

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Wszelaka-Rylik, M., Gierycz, P. Isothermal titration calorimetry (ITC) study of natural cyclodextrins inclusion complexes with drugs. J Therm Anal Calorim 111, 2029–2035 (2013). https://doi.org/10.1007/s10973-012-2251-4

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  • DOI: https://doi.org/10.1007/s10973-012-2251-4

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