Characterization of autoxidation products of the antifungal compounds econazole nitrate and miconazole nitrate

Oxidative degradation of pharmaceuticals: Theory, mechanisms and inhibition

“…The primary products of ether oxidations are α‐hydroperoxides, which may further degrade to aldehydes, ketones, alcohols, and carboxylic acids. The AIBN‐induced oxidation (77°C; 90% ethanol) of econazole and miconazole nitrate (Figure 6), which differ in structure by one chloride substitution, occurred at both benzylic hydrogen positions, which, incidentally, are also in an α‐position to the ether moiety 104. Interestingly, only miconazole nitrate produced appreciable imidazole oxidation.…”

Evaluation of Solution Oxygenation Requirements for Azonitrile-Based Oxidative Forced Degradation Studies of Pharmaceutical Compounds

“…The practice of using pressurized oxygen headspace4,8 during the azonitrile‐initiated stress experiment has presumably arisen from a desire to maximize the formation of alkyl hydroperoxy radicals in the belief that such species provide the most representative model of autoxidiation. Indeed, this is a reasonable procedure and is consistent with the current understanding of peroxy radicals as the central species involved in solid‐state oxidative degradation in pharmaceutical formulations 11.…”

“…, only a minority of companies are currently routinely utilizing peroxy radical‐based oxidative forced stress procedures 3. The most widely used peroxy radical‐based method is the use of azonitrile‐type radical initiators such as 2,2′‐azobisisobutyronitrile (AIBN)5–10 and 4,4′‐azobis‐4‐cyanovaleric acid (ACVA)4,6 solutions to create the peroxy radical oxidation environment 11. These azonitrile radical initiators, which have been used for many years in polymer chemistry,12–14 thermally decompose to expell nitrogen, leaving two cyanoalkyl radicals that can rapidly react with oxygen to form peroxy radicals (Scheme ).…”

“…Despite a small body of literature suggesting that such radical initiators are successful models of autoxidation in pharmaceutical formulations, there is not yet a consensus on the appropriate experimental conditions for the stress experiment. For example, different solvents and reagent concentrations are used, and some investigators advocate that azonitrile stress be conducted in a pressurized oxygen environment4,8 while others conduct experiments under ambient atmosphere 5,6,9,10,16. The adequate oxygenation of the stress solutions is a particularly important experimental variable.…”

Design, Characterization, and In Vitro Evaluation of Antifungal Polymeric Films

“…3. Figure 3a shows the TG curves of the starting materials: there was no weight loss until ECN melting (162-166°C), while the loss of ECN mass at 168°C could be attributed to the decomposition of drug after melt (44). The CH powder presents a characteristic chain degradation around 300°C and CB shows two peaks at 80°C (water evaporation) and at 250-350°C, referred to a thermal degradation at which CB melts and decomposes sequentially (45).…”