Stability of Sunitinib in Oral Suspension

Abstract

Sunitinib is a novel, oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity. No liquid formulation of sunitinib malate is commercially available for pediatric administration. To prepare extemporaneously an oral liquid formulation of sunitinib malate from commercially available capsules and study its chemical and physical stability in suspension at room temperature and under refrigeration at 4 degrees C. Six independent samples were prepared by mixing the contents of 3 sunitinib malate capsules (each equivalent to 50 mg of sunitinib) with 15 mL of a 1:1 mixture of Ora-Plus:Ora-Sweet solution to yield a final concentration of 10 mg/mL. Suspensions were stored in amber plastic bottles with child-resistant caps. Three samples were refrigerated at 4 degrees C and 3 were stored at room temperature. Aliquots from each bottle were obtained on days 1, 2, 3, 5, 7, 14, 21, 30, and 60 and diluted to a final concentration of 300 ng/mL with 500 ng/mL of clozapine in 50% acetonitrile. Sunitinib concentrations were then measured by a liquid chromatography-tandem mass spectrometry assay validated in our laboratory. At room temperature and under refrigeration at 4 degrees C, sunitinib in a 10-mg/mL suspension of sunitinib malate with Ora-Plus:Ora-Sweet 1:1 maintained greater than 96% of its initial concentration for 60 days. Visual appearance (color and consistency) and odor of drug suspension remained unchanged during the study. Sunitinib is stable in an oral suspension prepared from commercially available capsules for at least 60 days at room temperature and refrigeration at 4 degrees C. This liquid formulation is better suited for administration to children and adults with cancer who cannot swallow sunitinib capsules.