RESUMEN
SU5416, the first in a new class of anti-angiogenesis agents, is an insoluble and neutral molecule which requires a formulation containing Cremophor EL, ethanol, and polyethylene glycol. SU010382, a prodrug of SU5416, was designed as N-Mannich base to provide a basic handle that could be exploited to increase the compound's solubility. Though an increase in solubility was obtained, the inherent hydrolytic instability of SU010382 presented a major challenge in formulation development. The aim of this study is to design a stable intravenous formulation of SU010382 at 2 mg/mL equivalent to the 1.5 mg/mL clinical formulation of SU5416 without a high surfactant/co-solvent content. A stable formulation of SU010382 was successfully designed using a combination of adjusted pH and complexation with sulfobutyl-ether-beta-cyclodextrin. This formulation was designed as a lyophilized product to further increase stability. The lyophilized formulation was stable for at least 6 months at 40 degrees C/75% relative humidity, reconstituted completely within 1 min, and was stable for at least 24 h at 25 degrees C following reconstitution.