Injectable Suspension Formulation of Axitinib

Axitinib, a poorly aqueous-soluble small molecule (0.2 µg/mL at physiological pH) with a molecular weight of 386.5 g/mol, was micronized (D₅₀: <3 µm and D₉₀: <5 µm) and compounded as a stable injectable opaque-white ophthalmic suspension (D₁₀: <3 µm, D₅₀: <7 µm and D₉₀: <10 µm) at physiological pH using polysorbate 80, a wetting agent, before the addition of a phosphate-buffered suspending solution containing sodium carboxymethylcellulose, a viscosity-enhancing agent, and sodium chloride, a tonicity agent, and pH adjusted to neutral pH using either 1N sodium hydroxide or 1N hydrochloric acid. The suspension formulations were prepared at 10 and 40 mg/mL concentrations, and further diluted with the placebo formulation vehicle to achieve the desired lower concentrations (0.3, 1.0, and 4.0 mg/mL). The suspension was then terminally sterilized and the final concentration of axitinib was confirmed via a high-performance liquid chromatography assay. All formulations were stored at room temperature and protected from light. Immediately before dosing, each test article was vortexed for approximately 2 minutes.