Complexation studies of cyclodextrins with tricyclic antidepressants using ion-selective electrodes

The complexation of six tricyclic antidepressant drugs [amitriptylin (AMN), nortriptylin (NRN), imipramin (IMN), doxepin (DXN), protriptylin (PTN), and maprotilin (MPN)] with alpha- and beta-cyclodextrins (CDs) using ion-selective electrodes (ISEs) as drug ion sensors is described. Binding parameters were calculated by nonlinear fitting of the model described by the Scatchard equation, to the experimental data of a titration of a CD solution with the ion of interest. One binding site (the CD cavity) was found in all cases with both CDs. The calculated association constants at 25 degrees C using CD concentrations in the range of 0.0100-0.0010 M, varied from 4.81 x 10(3) M-1 (MPN) to 23.9 x 10(3) M-1 (AMN) in the case of beta-CD and from 50 M-1 (DXN) to 123 M-1 (MPN) in the case of alpha-CD. The precision for the estimation of the binding parameters was 0.1-5.0% (within-run RSD%) and 8-10% (between-run RSD%; n = 3). The complexation of the drugs with beta-CD was also examined as a function of temperature in the range of 5-37 degrees C; it was found to decrease by increasing temperature. Van't Hoff analysis gave good correlations (r greater than or equal to 0.989) for all drug ions studied. The estimates of the thermodynamic parameters indicate that the formation of inclusion complexes is enthalpy driven. A compensation plot based on the thermodynamic parameters delta H and delta S resulted in a linear relationship, which is indicative of a common type of force involved in the complexation of drugs to beta-CD.