Stability and stabilization studies of TAK-599 (ceftaroline fosamil), a novel N-phosphono type prodrug of anti-methicillin resistant Staphylococcus aureus cephalosporin T-91825

TAK-599 (known as ceftaroline fosamil) is a novel N-phosphono type prodrug of a cephalosporin compound, T-91825, (hat exhibits strong activity against methicillin resistant Staphylococcus aureus (MRSA). The stability and stabilization of TAK-599 were investigated by kinetic analysis focused oil crystallinity and moisture content. Initially if was planned to develop TAK-599 as an injectable formulation using the amorphous solid powder prepared by lyophilization. However, amorphous of TAK-599 free form was found to be chemically unstable even when stored at VC, and thus development was focused oil the crystalline material. After exhaustive screening of crystallization condition, the monoacetic acid solvate was found to yield TAK-599 in a crystalline form. Physico-chemical properties were studied to identify the key factors affecting the stabilization of TAK-599 in order to improve long-term stability, and the results indicated that the crystallinity of TAK-599 correlated with stability. Furthermore, moisture content was also identified in our studies as all important factor in stabilizing TAK-599. TAK-599 containing about 3%, moisture was found to be the most stable form. It was concluded that both sufficient crystallinity and strict moisture control of TAK-599 were essential to maintain long-term stability at 25 degrees C.