Long-term Stability of Cocaine Hydrochloride Aqueous Solution 50 mg/mL (5%) at Room Temperature and at 5°C ± 3°C in Glass Bottles.

The objective of this study was to investigate the stability of cocaine hydrochloride 50 mg/mL (5%) aqueous solution stored in glass bottles at 5°C ± 3°C or at room temperature. Ten bottles of cocaine hydrochloride 50 mg/mL were prepared under aseptic conditions. Five were stored at 5°C ± 3°C and five at room temperature. pH measurements, optic density measurements at different wave-lengths, and optic microscopic observations were performed periodically during the storage. A forced-degradation test with hydrochloric acid 12M and NaOH 5M with and without heating at 100°C was also performed. The concentrations were measured by high-pressure liquid chromatography with photodiode-array detection. Stability of the solutions was defined as the period for which the one-sided 95% confidence interval of the common regression line remains superior to 90% of the initial concentration as recommended by the U.S. Food and Drug Administration. The forced-degradation tests did not influence the chromatographic peaks of the studied component. No significant change of optic density was seen and no crystals were observed with the optic microscope during the study. The solutions stored at 5°C ± 3°C or at room temperature maintained 90% of their concentration after 24 days. During this period, the pH of the solution decreased from 5.39 to 4.34 at 5°C ± 3°C and from 5.37 to 3.44 at room temperature. In order to alleviate adverse reactions to the eye with too low pH, we propose a period of validity of 15 days at 5°C ± 3°C and 48 hours at room temperature. During this period, the degradation of the preparation was lower than 10%, and the values of pH were higher than 4.0.