STUDIES ON THE STABILITY OF SUPHACETAMIDE AND DEGRADATION PRODUCTS

Abstract

The degradation reactions and metabolic transformation of sulphacetamide and suphanilamide have been reviewed along with the analytical techniques used for detection, identification and assay of these compounds. The various physicochemical and biological factors affecting the formulation of eye-drops have been discussed The photolysis of sulphacetamide and sulphanilamide has been studied at pH 1-13 in buffered and unbuffered solutions using thin layer chromatography and spectrophotometric techniques. Sulphanilamide has been shown to be an early intermediate in the degradation sequence of sulphacetamide in both acid and alkaline solutions. The various degradation products of sulphacetamide have been separated on fluorescent silica gel layers and some of these have been identified as sulphanilamide, sulphanilic acid, azobenzene-4, 4-disulphonamide, azoxybenzene-4, 4-disulphonamide, azobenzene-4, 4-disulphomic acid and blue product. On the basis of partial characterization a skeleton of the possible structure of blue product has been suggested Various methods available for the assay of sulphonamides have been examined and found to be inapplicable to the present work. A multicomponent spectrophotometric method has, therefore, been developed to assay sulphacetamide, sulphanilamide and the major degradation products, i.e. azobenzene-4, 4-disulphonamide and blue product, during photolysis, and to follow the kinetics of degradation. A number of reaction schemes for the degradation pathways of sulphacetamide and sulphanilamide have been proposed The photolysis of sulphacetamide proceeds by a second-order reaction at pH 1-13. The log k-pH profiles for sulphanilamide and sulphacetamide are non-linear, which is most likely to be due to a difference in the state of ionization of the molecules at the reaction pH. The buffer salts (citrate, borate) catalyse the rate of photolysis probably by facilitating singlet to triplet transitions and further conversions to the degradation products Sulphacetamide undergoes hydrolysis of sulphanilamide which may be attacked on the aromatic-NH2 group and/or the –SO2NH2 group leading to the formation of azo and azoxy derivatives and/or the blue product and sulphanilic acid through radical mechanism. The formation of the azo derivative appears to be favored in alkaline solution, whereas that of the blue product in acid solution. The apparent quantum yields for the photolysis of sulphacetamide and sulphanilamide at pH7 (phosphate buffer) and 0.17 and 0.33 respectively Among the antioxidants studied, a combination of sodium metabisulphite or thiourea and sodium edentate appears to be most effective for the photo stabilization of aqueous solutions of sulphacetamide and sulphanilamide