Accelerated Conditions for Stability Assessment of Bulk and Formulated Cefaclor Monohydrate

Abstract

The stability of cefaclor monohydrate drug substance and formulated products was studied under accelerated conditions in order to provide a rapid indication of differences that might result from a change in manufacturing process or source of the sample. The USP stability-indicating related substances assay was used to assess the extent of sample degradation. An Arrhenius study of drug substance stability from 45 to 70 degrees C predicted a degradation rate consistent with that observed in room-temperature studies. Qualitative degradation profiles of samples held at 65 degrees C for 2 weeks were also very similar to those of samples held at room temperature for 2 years. Based on these results, additional studies were conducted at 65 degrees C for 2 weeks on drug substance and formulated product samples. Stability differences were observed among some capsule formulations that had also exhibited real time differences. In some studies, rapid degradation after 5 days was observed at 65 degrees C followed by a slower rate from 5 to 15 days. Similar behavior was observed for cefaclor monohydrate containing high amounts of amorphous cefaclor, suggesting that differences in amorphous content could be an explanation for stability differences observed in various samples. The accelerated conditions were shown to differentiate samples and can provide a rapid indication of relative stability.