Behavior of tricyclic antidepressants in aqueous solution:: Self-aggregation and association with β-cyclodextrin

Conductivity measurements have been carried out to study the behavior of the aqueous solutions of three tricyclic antidepressant drugs (TCAs), imipramine, desipramine, and amitriptyline hydrochlorides, in the absence and in the presence of beta -cyclodextrin (beta -CD) at 25 degreesC. The TCAs studied herein have been found to show an aggregation behavior in aqueous solution. A model has been proposed to determine the aggregation number of small aggregates from conductivity measurements. Several parameters, such as the aggregation number, Na,, the critical aggregation concentration, cac, and the dissociation degree of the aggregates, beta, have been determined. In the presence of beta -CD, the TCAs form inclusion complexes with 1:1 stoichiometries and binding constants in the range of 1500-3000 M-1. The ionic molar conductivities of the TCA(+)ion, free in solution, lambda (0)(TCA+) associated with the beta -CD, lambda (0)(CD/TCD+), and self-aggregated, lambda (0)(ag) have been calculated as well. The effect of beta -CD on the aggregation behavior of the drugs has been evaluated by determining the apparent critical aggregation concentration, cac* (the cac for the ternary beta -CD/TCA/ H2O systems), and the dissociation degree. Complementary measurements of pH, UV-vis, and fluorescence as well as a preliminary simulation of the complexes from manual docking studies were done to support some evidence.