Spectrophotometric and thermodynamic studies of the charge-transfer complexation of tranexamic acid with chloranilic acid

Abstract

Background: Tranexamic acid is a synthetic analogue of lysine that is clinically useful as an antifibrinolytic agent. Due to its lack of chromophores and aromaticity, chemical derivatization is necessitated and outcomes are often poor and/or associated with low sensitivity and poor stability.

Objective: To develop a colorimetric method for the determination of tranexamic acid (TXA) following the optimization and parameterization of the charge-transfer (CT) complexation of the drug with chloranilic acid (CAA).

Method: The method involved the utilization of TXA as n-electron donor and CAA as π-acceptor in methanol to generate a CT complex. Factors contributory to the formation and stabilization of the complex were optimized. The Benesi-Hilderbrand equation was used to estimate the molar absorptivity and formation constant of the CT band before its application to dosage form analysis.

Results: The CT band which absorbed maximally at 520 nm was associated with molar absorptivity of 807 Lmol^-1cm^-1 and a large formation constant (1.14x10⁴). The calculated physicochemical properties including transition energy (2.303eV), oscillator strength (0.267), transition dipole moment (5.455 Debye), resonance energy (1.159 eV), ionization potential (8.679 eV) and dissociation energy (5.276 eV) as well as the thermodynamic parameters were indicative of a highly stable charge-transfer complex. Under optimal conditions, the assays of the drug were linear over the range 10-100 μg/mL and the method was accurate and reproducible (inter-day relative errors and standard deviations not greater than 2.92% and 3.40% respectively). When applied to dosage forms, there was no statistical difference in the mean recoveries of the new method when compared to reference method.

Conclusion: The new method is rapid, accurate and precise. It can serve as alternative to the routine analysis of tranexamic acid in bulk and dosage forms.

Keywords: Tranexamic acid, Chloranilic acid, Charge-transfer complexation, Physico-chemical studies, Thermodynamic studies