Potentiometric and spectroscopic study of isoniazid – an anti-tubercular drug

Abstract

The copper, nickel and zinc complexes of isoniazid (ISO, isonicotinic acid hydrazide), an anti-tubercular drug, have been investigated to determine  whether these metal-ions improve the permeability and bioavailability of the drug. Since such properties of isonazid depend on its solution speciation,  the latter was investigated by determining the equilibrium constants for the reaction of H⁺, Cu(II), Ni(II) and Zn(II) with isonazid in aqueous solution at  25.00 ± 0.01 °C and 0.15 M (NaCl), using glass electrode potentiometry. The structure of the copper complex of isoniazid was investigated using  ultraviolet-visible spectroscopy. The results support the structures postulated from the potentiometric data. This study also considered membrane  permeability using a Franz cell and octanol/water distribution coefficients. Distribution coefficient studies showed that ISO and its metal complexes are  hydrophilic. The incorporation of a metal-ion improves the hydrophilicity of the ligand. The presence of a metal ion greatly enhanced the permeation of  ISO through an artificial membrane in the order Cu(II) > Ni(II) > Zn(II) > ISO at pH 2 and Zn(II) > Ni(II) > ISO > Cu(II) at pH 4.