Evaluation of the Cefalexin Drug Degradation Profile in Pharmaceutical Capsule Forms Based on Forced Degradation Studies

Abstract

Different forced degradation conditions were tested to evaluate the degradation profile of cephalexin (CEF). Samples of the active pharmaceutical ingredient and the corresponding finished product in capsule form were exposed to stress conditions, namely acid hydrolysis (1 M HCl), basic hydrolysis (0.04 M NaOH), oxidation (H₂O₂ 0.3% and the presence of metal ions (50 mM FeCl₃)), thermal treatment at 60 °C, photolytic treatment (2.4 klux h and 400 W h/m²) and controlled humidity (25 °C and 75% relative humidity). The generation of potential degradation products was evaluated. This study allowed for the development of a stability-indicating method using ultrahigh-pressure liquid chromatography coupled with diode array detection and high-resolution mass spectrometry techniques, as well as providing information about possible degradation routes and detection of unknown compounds. The results obtained under forced degradation conditions showed that CEF is generally stable when exposed to temperatures up to 60 °C, ultraviolet light or visible light in the 300–800 nm wavelength range and 75% relative humidity. However, under acidic, basic, hydrogen peroxide and metal ion oxidative conditions, CEF showed degradation susceptibility, as demonstrated by the decrease in content and the formation of degradation products. The results obtained during forced degradation highlight the need for careful evaluation during studies of accelerated stability and the long-term duration of the product, with emphasis on the formation of a degradation product that was observed under all applied stress conditions. This study indicates that caution should be taken regarding hydrolysis of the active pharmaceutical ingredient (API).