PHARMACEUTICAL DEVELOPMENT OF A PARENTERAL FORMULATION OF THE NOVEL ANTITUMOR AGENT CARZELESIN (U-80,244)

The aim of this study was to design a parenteral dosage form for the i nvestigational cytotoxic drug carzelesin. A stable formulation in PET (Polyethylene glycol 400/absolute ethanol/Tween 80, 6:3:1, v/v/v) was developed. The prototype, containing 0.50 mg carzelesin in 2.0 ml PET formulation, was found to be the optimal formulation in terms of solub ility, stability and dosage requirements in phase I clinical trials. Q uality control of the formulation showed that the pharmaceutical prepa ration of carzelesin in PET is not negatively influenced by the manufa cturing process. Shelf life studies demonstrated that the formulation is stable for at least 1 year, when stored at -30 degrees C in the dar k. In addition, the stability of carzelesin in the PET formulation is discussed as a function of temperature, additives and after dilution i n infusion fluids.