Kinetic Study on Crystallinity Change and Degradation Process of Cefixime Trihydrate during Drying

Abstract

Compounds with hydrated structures can degrade easily. Therefore, investigation of the degradation process of hydrated compounds is imperative from the viewpoint that the hydration status often contributes to the stability and even affects the spatial structure of compounds. Cefixime Trihydrate, a widely used antibiotic, is one of such typical examples, in which the hydrated water molecules have been revealed to contribute significantly to its crystallinity. Previous studies have shown that an over-drying process could cause the hydrolysis decomposition of Cefixime Trihydrate. However, no quantitative analysis has been reported. Herein, we report a systematic evaluation of the influence of over-drying on crystal condition. Analysis of the correlation between the water content and crystallinity indicated the importance of hydrated water molecules toward the stability of Cefixime. The Avrami equation was also employed to fit the correlation data between the increase of degradation ratio and the decrease of crystallinity. For the first time, the crystallinity was quantified to determine the stability of the crystal lattice, which depends on water content. It was confirmed that over-drying process could cause the destruction of the crystal lattice and lead to the acceleration of the degradation rate. We expect our results will deepen the comprehension of the relationships among the degradation rate, the hydration state, and the crystallinity, helping optimize the storage conditions of products in chemical plant scale manufacturing with more convenience.