Characterization of the hydrochlorothiazide: b-cyclodextrin inclusion complex. Experimental and theoretical methods

ONNAINTY, R; SCHENFELD, E.M.; QUEVEDO, M.A.; FERNANDEZ, M.A; LONGHI, M.R.; GRANERO, G.E.

AMER CHEMICAL SOC

Lugar: Washington; Año: 2013 vol. 117 p. 206 - 206

ydrochlorothiazide (HCT) is one of the most commonly prescribed antihypertensive drugs. In an attempt to gain an insight into the physicochemical and molecular aspects controlling the complex architecture of native β-cyclodextrin (β-CD) with HCT, we performed multiple-temperature−pH isothermal titration calorimetric measurements of the HCT:β-CD system, together with proton nuclear magnetic resonance spectroscopy (1H NMR), phase solubility analysis, and molecular modeling methods. The AL-type diagrams, obtained at different pH values and temperatures, suggested the formation of soluble 1:1 inclusion complexes of β-CD with HCT. The corresponding stability constants (K1:1) were determined by phase solubility studies and compared with those obtained by ITC, with good agreement between these two techniques being found. The three-dimensional array of the complex was studied by 1H NMR and molecular modeling methods. Both techniques confirmed the formation of the i