SOLUBILITY AND STABILITY CHARACTERIZATION OF ZILEUTON IN A TERNARY SOLVENT SYSTEM

Zileuton (ABT-077) is a 5-lipoxygenase inhibitor with poor aqueous sol ubility. Using an extreme vertices experimental design and an empirica l response surface analysis, both the solubility and pseudo-first-orde r degradation rate constants of zileuton were determined in a ternary solvent system consisting of water, ethanol and propylene glycol. The logarithm of the solubility increased curvilinearly with increasing we ight fraction ethanol or weight fraction propylene glycol in the solve nt system and decreased linearly with increasing dielectric constant o f the medium. The degradation rate increased linearly with increasing weight fraction ethanol or weight fraction propylene glycol and the lo garithm of the degradation rate constant increased linearly with respe ct to the reciprocal of the dielectric constant of the medium. The deg radation products observed were the hydroxylamine, syn- and anti-oxime s of zileuton, implying that a solvolysis reaction at the amide bond o ccurs in all solvent compositions.