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

Conductivity measurements have been carried out to study the behavior of th e aqueous solutions of three tricyclic antidepressant drugs (TCAs), imipram ine, desipramine, and amitriptyline hydrochlorides, in the absence and in t he presence of beta -cyclodextrin (beta -CD) at 25 degreesC. The TCAs studi ed herein have been found to show an aggregation behavior in aqueous soluti on. 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 t he dissociation degree of the aggregates, beta, have been determined. In th e presence of beta -CD, the TCAs form inclusion complexes with 1:1 stoichio metries and binding constants in the range of 1500-3000 M-1. The ionic mola r conductivities of the TCA(+)ion, free in solution, lambda (0)(TCA+) assoc iated 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 aggregat ion behavior of the drugs has been evaluated by determining the apparent cr itical aggregation concentration, cac* (the cac for the ternary beta -CD/TC A/ H2O systems), and the dissociation degree. Complementary measurements of pH, UV-vis, and fluorescence as well as a preliminary simulation of the co mplexes from manual docking studies were done to support some evidence.