Chemical instability of cefaclor in simple suspensions alkalinized with magnesium oxide and the structural elucidation of the degradation products.

A simple suspension method, where solid formulations are soaked in water (55 °C) and suspended followed by tube administration, has been widely used in Japan for patients with dysphagia. However, information on the chemical stability of drugs concomitantly suspended with acidic or basic ones is insufficient. Cefaclor, a β-lactam antibiotic, is commonly used to treat various infectious diseases. This drug has been reported to be unstable depending on pH and temperature. Also, magnesium oxide (MgO) is a typical alkaline drug frequently prescribed as a laxative. These drugs are occasionally taken together, particularly by older patients. In this study, we have investigated the chemical stability of cefaclor in a concomitant simple suspension with MgO. A cefaclor capsule with or without an MgO tablet was subjected to the simple suspension method, and the suspensions were analyzed by high-performance liquid chromatography. No degradation was observed for the suspension of cefaclor alone, whereas when concomitantly suspended with MgO, the peak intensity of cefaclor considerably decreased, and two degradation peaks appeared. The results showed that co-suspensions with MgO should be avoided. The degradation products were isolated and spectroscopically identified to be piperazine derivatives including a novel one. Their plausible formation mechanisms have also been proposed.