Investigation on the endothermic event of cephalexin monohydrate in differential scanning calorimetric curve

Cephalexin BP, USP an orally active, semisynthetic cephalosporin antibiotic is made into different dosage forms. However, its melting point and decomposition temperature, two important formulation parameters, have not been clearly defined. Melt temperature at 196–198, 321–326.8 °C or unknown has been as reported in the literature. Furthermore, the study differential scanning calorimetry published by El-Shattawy et al. exhibited an exotherm with a maximum peak of transition at 195 °C. Five approaches, one- and two-step DSC, MEL-TEMP apparatus, visual inspection of powder before and after heat stress to simulate an industrial operation procedure, UV and HPLC assays, were used in this study. A sample was heated to one of the several predetermined temperatures; the calorimeter chamber was next quench-cooled to room temperature, while the sample remained inside doubly covered. It was then reheated to 250 °C to explore the endotherm at approximately 80 °C and the exotherm at 190 °C that we found in the one-step DSC study. From the integrated results of these five studies, we concluded that the melting of cephalexin is atypical and cephalexin monohydrate absorbs energy from 31.5 to 121.9 °C (with dip temperature at 69.5 ± 7.6 °C, n = 6) to allow both bound and free water to evaporate. If insisted on removing the bound water from the cephalexin monohydrate powder, the added enthalpy may endanger drug stability as the degradation starts much earlier than its actively decomposed temperature ranging from 176.2 to 200.3 °C (with apex temperature at 196.9 ± 0.3 °C, n = 6). The data also disclosed that the hydrate of cephalexin exhibits interaction with crystal structure.