Stability studies of hydralazine hydrochloride in aqueous solutions.

The hydrolysis kinetics of hydralazine hydrochloride was studied at pH 1 to 12 at 35 degrees, 50 degrees, and 70 degrees C. The hydrolysis takes place by water attack on the dicationic and the cationic forms of the drug. In addition there is hydroxyl attack on the cationic and the neutral forms of the drug. The drug is not subject to attack by acetate and carbonate buffers, but its decomposition is catalyzed by HPO4 = of the H2PO4-, HPO4 = buffer system. The hydrolysis rate follows first order kinetics under nitrogen, at constant pH, temperature, and buffer concentration. The pH profile indicates that hydralazine has maximum stability near pH 3.5. The drug decomposes to phthalazine and other products. The Arrhenius activation energy was found to be 17.9 kcal/mol at pH 3.5 and the time required for 10% loss (t0.9) was estimated from the Arrhenius parameters to be 1.56 years at 25 degrees C.