Solubility and stability of cediranib maleate

Abstract

Cediranib is a tyrosine kinase inhibitor that is used to treat ovarian cancer. The drug is administered as tablets containing the somewhat water-soluble salt cediranib maleate. However, the oral bioavailability is low and variable due to first-pass elimination. Enhanced solubilization and stabilization of cediranib can allow for alternative route of administration. The purpose of this study was to investigate the aqueous solubility of cediranib and its chemical stability in aqueous solutions. The aqueous solubility of cediranib maleate is strongly dependent on the ionization of both cediranib and the maleate counterion showing maximum at pH where the monovalent cediranib cation can form an ion pair with the monovalent maleate anion. The monovalent cediranib cation also had the highest affinity for the γ-cyclodextrin central cavity resulting in optimum solubilization. Cyclodextrin complexation did enhance the cediranib stability in aqueous solution and addition of small amount of riboflavin increased the stability even further. The degradation pathway of cediranib in acidic aqueous solutions was determined.