Nanosuspension Formulation and Optimized Pharmacokinetics of Anti-Neoplastic IFT-156

摘要

The insoluble anti-neoplastic agent IFT-156 wasformulated as a crystalline nanosuspension using acombined process of microprecipitation, followed byhomogenization in the presence of stabilizingsurfactants. IV pharmacokinetics were studied inrats. In comparison with a conventional organicsolution formulation, the nanosuspension permittedconsiderably higher dosing (15 vs. 0.25 mg/kg), andgave a prolonged plasma concentration level. Basedupon the mechanism of action of cell-cycle sensitiveoncolytics, this sustained activity is expected to behighly efficacious, as indicated in preliminary efficacystudies. Tissue distribution studies were consistentwith an IV depot effect, indicated by thepharmacokinetics.