Temperature effect on the complex formation between tricyclic antidepressant drugs (amitriptyline or imipramine) and hydroxypropyl-β-cyclodextrin in water

Abstract

The molecular encapsulation of two tricyclic antidepressants (TCA) drugs, amitriptyline and imipramine, by a glycosidic receptor, 6-hydroxypropyl-β-cyclodextrin (HPBCD), has been carried out in water solution by means of conductometric studies at different temperatures ranging from 15 °C to 45 °C. Conductivity measurements of aqueous solutions of the drug were performed: (i) in the absence of HPBCD, as a function of drug concentration; and (ii) in the presence of HPBCD, as a function of HPBCD concentration. Both drugs, amitriptyline and imipramine, form inclusion complexes characterized by a 1:1 stoichiometry and an association constant (\(K_{\rm HPBCD:TCAH^+}\)) in the range of 500–1200 M−1. The ionic molar conductivities at infinite dilution of the free (\(\lambda_{\rm TCAH^+}^0\)) and complexed (\(\lambda_{\rm HPBCD:TCAH^+}^0\)) drugs have been calculated from these conductivity data as well. From the dependency of the association constant on temperature, changes on the enthalpy, ΔH0, entropy, ΔS0, and heat capacity at constant pressure, \(\Delta C_{\rm p}^{0}\) , have been determined. This thermodynamic information, which reveals that the complexes formed by HPBCD and the antidepressant drugs, AMYTPH+ and IPRH+, are enthalpy driven at T ≥ 25 °C but entropy driven at T < 25 °C, points to the contribution of van der Waals interactions, hydrophobic effect and solvent reorganization, as the main driven forces promoting the interaction. The analysis of these association processes was also used to elucidate the potential viability of using HPBCD as a vector of these antidepressant drugs.