An evaluation of spectral and statistical parameters of ion pair complexation of Zafirlukast using chromogenic dyes in solid dispersion-based formulations.

ABSTRACT

The purpose of present work was to develop a novel analytical method for orally given leukotriene antagonist Zafirlukast (ZST), present in Meglumine and Eudragit EEPO based solid dispersion formulation. Four simple, extraction-free, fast, and economical methods based on charge transfer complexation among nitrogen of ZST with sulfonyl group comprising chromogenic mediator bromophenol blue (BPB-Method B), bromothymol blue (BTB-Method C) and bromocresol green (BCG-Method D). The first method (A) is based on the analysis using 0.1 M HCl as a solvent at λmax 242 nm while chromogenic methods yield color complex at λmax 415 nm (BPB-Method B), λmax 420 nm (BTB-Method C) and λmax 435 nm (BCG-Method D). The Beer's Law stayed linear in the concentration ranges of 1-10, 10-75, 5-40 and 15-100 µg/ml for methods A, B, C and D, respectively. The spectral and thermodynamic characterization of each method was carried out by the application of Molar Absorptivity, LOD, LOQ, Association Constant and Gibbs free energy (ΔGo). The methods were statistically optimized and evaluated by F-Distribution Value, P-Value, Shapiro-Wilk P-Value, regression analysis, Q-Q plot, prediction interval, residual histogram and plots. Various experimental conditions affecting the complexation and stability of chromogenic complexes are cautiously studied including optimal temperature, chromogenic agent volume, color stability, recovery, precision and accuracy. All the measurements were executed under ICH guidelines. It can be established that proposed would be an appropriate prospective analytical approach for estimation of ZST in pure bulk, solid dispersions and dosage forms.