Stability of Sunitinib in Oral Suspension

Abstract

Background:

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.

Objective:

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 °C.

Methods:

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 °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% acetonttrile. Sunitinib concentrations were then measured by a liquid chromatography–tandem mass spectrometry assay validated in our laboratory.

Results:

At room temperature and under refrigeration at 4 °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.

Conclusions:

Sunitinib is stable in an oral suspension prepared from commercially available capsules for at least 60 days al room temperature and refrigeration at 4 °C. This liquid formulation is better suited for administration to children and adults with cancer who cannot swallow sunitinib capsules.