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ONCOLOGY

Stability of Sunitinib in Oral Suspension

Assistant Member, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN; Assistant Professor, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis

Robbin Christensen, BSPharm

Clinical Research Pharmacist, Department of Pharmaceutical Services, St. Jude Children's Research Hospital

Patton Minkin, BS

Research Technician, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital

Clinton F Stewart, PharmD

Member, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital

Wayne L Furman, MD

Member, Department of Oncology, St. Jude Children's Research Hospital; Professor, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center

Sharyn Baker, PharmD PhD

Associate Member, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital

Reprints: Dr. Navid, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, TN 38112, fax 901/521-9005, fariba.navid{at}stjude.org

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% acetonitrile. 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 at 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.

Key Words: oral solution, stability, sunitinib

Published Online, June 24, 2008. www.theannals.com, DOI 10.1345/aph.1K654