Study of the forced degradation of isoconazole nitrate in bulk drug and cream formulations

摘要

Bulk drug and cream formulations of isoconazole were subjected to the following ICH-recommended stress conditions: hydrochloric acid (0.1 M), sodium hydroxide (0.1 and 1 M), and hydrogen peroxide (3%). Photostability was monitored for 60 h in a UV chamber. Analysis of drug degradation was performed using an HPLC method that had been validated for linearity, range, precision, accuracy, limits of detection and quantification, and selectivity and robustness in accordance with the criteria established by Resolution 899 of the Brazilian National Health Surveillance Agency (ANVISA). When isoconazole cream was exposed to a light source, the isoconazole content decreased slightly, but no degradation products were formed as indicated by the absence of additional peaks in the HPLC chromatogram. The drug was found to be unstable in both the bulk form and in the cream formulation when subjected to alkaline hydrolysis conditions, exhibiting reductions of ca. 43 and 70% of the initial content, respectively. Different sample solutions that had been subjected to alkaline degradation indicated, through subsequent pH adjustments and UV analysis, the presence of an isbsbestic point at 275 nm, suggestive of a reversible phenomenon in alkaline media. Reversibility by bringing the pH back to the initial value may be a valuable tool for identifying real degradation processes. In contrast to the drug's instability under alkaline conditions, isoconazole was found to be stable under both acid hydrolysis and oxidative conditions.