Instability of digoxin in acid medium using a nonisotopic method.

Abstract

A selective nonisotopic assay was used to investigate the digoxin hydrolysis rates at 37 +/- 0.1 degrees over the pH 1.1--2.2 range. The colorimetric method adopted is based on the use of a xanthydrol reagent after extraction with chloroform. The spectrofluorometric method specified in the dissolution test for digoxin tablets was nonspecific because of digoxigenin interference. Digoxin hydrolysis followed specific acid hydrolysis, and K values of the apparent first-order reaction varied from 0.0357 to 0.0027 min-1 over the pH range used. The effect of the dissolution medium on digoxin stability during the dissolution tests of the tablets also was studied. Water (the BP medium) and 0.6% HCl (the USP medium) were compared using the fluorometric method and the xanthydrol method. In the USP medium (pH 1.3), no hydrolysis was revealed by the fluorometric estimation whereas the xanthydrol method showed about 74% hydrolysis. In water, the two methods revealed no hydrolysis. The extent of hydrolysis after 1 hr in the USP medium was studied using three brands of digoxin tablets of differing dissolution characteristics. The fast dissolving brand showed relatively more hydrolysis than the slow dissolving tablets.