Multi-equilibrium system based on sertraline and β-cyclodextrin supramolecular complex in aqueous solution

Sertraline (SRT) is a widely used antidepressant whose poor solubility in water limits its oral applicability. Thus, the aim of this work was the evaluation of a multi-equilibrium system based on beta-cyclodextrin (beta CD) and SRT. The inclusion compounds (ICs) were investigated by infrared spectroscopy, isothermal titration calorimetry (ITC) and H-1 and 2D ROESY nuclear magnetic resonance experiments. SRT solubility was predicted in vitro in water and biomimetic fluids. The SRT in presence of beta CD at 1:1 and 1:2 molar ratios was more soluble than free SRT in all biomimetics media investigated. The FTIR-HATR showed that beta CD nu C-O-C stretching band was reduced in presence of SRT, suggesting the interactions between them. Additionally, titration process and Job's plot provided information on the ICs stoichiometry and evidenced the multi-equilibrium coexistence in aqueous solution. According to the ITC, SRT:beta CD interaction process was spontaneous and exothermic with a high affinity binding constant (K = 14,726 M-1). Additionally, the stoichiometry coefficient (n) was 1.63, which was comparable to that found by FITR-HATR. The H-1 and 2D ROESY verified multiple SRT sites included into the host cavity. Theoretical calculations depicted the relative energy of different proposed ICs structures, in which the 1:2 IC was the most stable. (C) 2011 Elsevier B.V. All rights reserved.