Abstract
Sodium bisulfite, which is frequently added as an antioxidant to ascorbic acid injections, was found to react with ascorbic acid and to effect the reduction of the vitamin concentration under anaerobic conditions. The rate of disappearance of ascorbic acid by sodium bisulfite in solution was pseudo first-order. In the pH range of 4 to 8 the dominating degradation process may be a reaction between monohydrogen ascorbate ion and bisulfite ion. The accompanying degradation of sodium bisulfite also followed the pseudo first-order. From the observed reaction rate constants of sodium bisulfite, the following Arrhenius equation was obtained. [numerical formula] k'obs at 25° was calculated as 2.30×10-4 hr-1. Assuming the average ambient temperature to be 25°, sodium bisulfite added to ascorbic acid injection will remain for as long a period as 300 to 400 days during its shelf-life. It was also found that cyanocobalamin was degraded by sodium bisulfite at considerably high velocity ; i.e., the half life of cyanocobalamin in aqueous solution of pH 5.3 at 25° was shortened to 180 and 38 minutes by the addition of 10 and 100 times moles of sodium bisulfite respectively. Therefore, cyanocobalamin injection is incompatible with commercially available ascorbic acid injections which generally contain sodium bisulfite. In conclusion, utilizing such an intra- and inter-formula reactive substance as sodium bisulfite seems not to be reasonable in the formulation of parenteral preparations.
