Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Abstract

In this paper, the flufenamic acid equilibria in aqueous solution and in two-phase organic solvent + aqueous solution are described and presented. The dissociation constants K a1 and K a2 were determined in MDM + water mixtures. The Yashuda-Shedlovsky extrapolation procedure has been used to obtain the values of K a1 and K a2 in aqueous solutions. The distribution ratio D was measured in the toluene + water system over a wide range of pH by the shaking flask method. Based on the results of potentiometric titrations in two-phase organic solvent (benzene, ethylbenzene, toluene, carbon tetrachloride, chloroform, chlorobenzene, and bromobenzene) + aqueous systems, and using models of single and multistep equilibria, the values of distribution constants K D and dimerization constants K dim were calculated. The influences of polarity of the applied solvents and pH of the aqueous phase, on the speciation of the particular forms of flufenamic acid in both phases, were demonstrated.

Chemical speciation of 2,3-dihydroxybenzoic acid complexes with some biologically essential metal ions in 1, 2-propanediol–water mixtures

“…Mixed solvents have been employed in different fields including pharmaceutical and analytical sciences (Zapała, 2011). The knowledge of dielectric constant of mixed solvents is required to predict the drug's solubility and chemical stability in a water-cosolvent mixture and the analyte behaviour in analytical methods (Abolghasem et al, 2004).…”

Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition

“…As FFA is an acidic drug, its solubility will increase in a higher pH solution [ 24 ]. The equilibrium solubility of FFA in PBS pH 6.8 at 37°C was 741.15 ± 6.27 µg/mL.…”

“…1 (b)]. Flufenamic acid is an ampholyte, having a basic group with pKa1 of 2.92 ± 0.01, an acidic group with pKa2 of 4.84 ± 0.04 and isoelectric point pH of 3.88 ± 0.03 [ 24 ]. At pH 4.5, FFA is largely in the neutral form (i.e., more than 75%).…”