Stability of hydralazine hydrochloride syrup compounded from tablets.

The stability of hydralazine hydrochloride in an oral syrup and with various adjuvants that might be used in a liquid formulation was studied. A syrup containing triturated hydralazine hydrochloride 50-mg tablets, a maltitol-based syrup vehicle, and other additives was prepared; the theoretical initial concentration of hydralazine hydrochloride was 1.25 mg/mL. Three samples were each stored at 5, 40, 50, 60, and 70 degrees C. Drug concentration was measured with high-performance liquid chromatography at times ranging from 2 to 23 days. In a second study, five 50-mL solutions were prepared: (1) hydralazine 1% with no pH adjustment, (2) hydralazine 1% with pH adjusted to 6.33, (3) hydralazine 1% and edetate disodium 1% with no pH adjustment, (4) hydralazine 1% and edetate sodium 1% with no pH adjustment, and (5) hydralazine 1% and sodium bisulfite 1% with no pH adjustment. Drug concentration was determined after storage for one week at 50 degrees C. There was apparent first-order degradation of hydralazine hydrochloride at all temperatures. An Arrhenius plot was used to calculate a shelf life of the syrup of 5.13 days at 25 degrees C. There were no changes in pH or physical appearance. In the second study, hydralazine hydrochloride solution turned yellow immediately after edetate sodium [corrected] was added; at one week the loss of drug was 29%. Addition of sodium bisulfite caused a more intense yellow coloration, and loss of drug at one week was 80%. Changes in pH were minimal. An Arrhenius plot showed that hydralazine hydrochloride was relatively unstable in an oral syrup at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)