Interaction of indomethacin–cyclodextrins in water by UV–Vis and ITC

Abstract

In this contribution, we analyze indomethacin–cyclodextrin (IMC–CD) inclusion by means of UV–Vis spectrophotometry and isothermal titration calorimetry (ITC) at 25 °C. Experiments were carried out in water at pH 5 and 7, using β-CD and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The study with UV–Vis was made using a molar relation method analyzing the spectra with Stability Quotients from Absorbance Data (SQUAD) to obtain the inclusion constants. In the case of ITC, the study was performed in aqueous-phosphate buffer at pH 7. The values of ΔG, ΔH, − TΔS were determined for the first time for the inclusion of IMC within β-CD and 2-HP-β-CD. Results for logK1:1 obtained by ITC agree reasonably with those determined by UV–Vis, confirming the formation of a complex of stoichiometric ratio IMC:CD of 1:1. Besides the confirmation of formation of the inclusion complex, inclusion is exothermic, and given the sign of entropy it is suggested that IMC inclusion is driven by release of water molecules from the cavity of CD. With the values of logK1:1 we construct the diagrams of species distribution to compare which CD performs better in including IMC.