The Effect of Various Additives on the Stability of Isoproterenol Hydrochloride Solutions

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Abstract
The effect of various additives on the rate of degradation of eight isoproterenol hydrochloride aqueous formulations was studied. In addition, the reaction was studied at various pH values and temperatures. From the latter data, activation parameters were determined. Rate constants increased from 10 to 100 times over a 25 degree increase in temperature. The activation energy for the reaction averaged approximately 25 kcal/mole. Ascorbic acid and sodium bisulfite appear to be the most efficient antioxidants in the system. Sequestering agents such as EDTA and citric acid do not appear to reduce the rate and, in one instance, EDTA seemed to enhance the degradation process. The reaction appears to be an oxidation of the catechol ring system of isoproterenol similar to that observed with epinephrine. Catecholamines such as isoproterenol and epinephrine are highly subject to degradative oxidation in solutions. A number of antioxidants and other substances are added to formulations containing these substances in an effort to retard this degradation. This study was undertaken to investigate the effect on the stability of the solutions. An attempt was also made to compare the interaction of isoproterenol with bisulfite and boric acid to the analogous interaction of the latter compounds with epinephrine.

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