Salts of Crizotinib with Dicarboxylic Acids: Structural Characteristic, Stability Analysis, and Solubility Performance

Crizotinib is a well-known anticancer medicine used for the targeted treatment of nonsmall cell lung cancer. The water solubility of crizotinib is quite low and restricts its oral bioavailability. In this work, saturated alkyl dicarboxylic acids were selected as salt formers, and two salts of crizotinib with malonic acid and adipic acid were prepared and comprehensively characterized by different analytical techniques. Both salts exhibited comparable physical and chemical stability in contrast to crizotinib. The most important point was that two salts demonstrated remarkable improved solubility in water, pH 1.2 HCl buffer, and pH 6.8 phosphoric acid buffer. In addition, according to the computation on the ADMETlab Web server, Caco-2 permeability remained on the same level after salt formation. Therefore, both salts are expected to promote further investigations toward the improvement of the crizotinib formulation.