The influence of formulation excipients on the stability of the novel antitumor agent carzelesin (U-80,244).

Abstract

The stability of carzelesin in a polyethylene glycol 400 (PEG 400)/absolute ethanol/polysorbate 80 (Tween 80) (6:3:1, v/v/v) formulation (PET formulation) was investigated as a function of the inter-batch variability of the three excipients. Twenty different PET formulations were tested and the stability of carzelesin in the PET formulation was found to be influenced by the type of PEG 400 used. Subsequent investigations showed that the pH of PEG 400, and consequently the pH of the PET formulation, was responsible for the variable stability characteristics of carzelesin in the PET formulation. The higher the pH of the PET formulation, the higher the rate of degradation of carzelesin in PET. The major degradation products were found to be U-76,073 and U-76,074.