Preparation, in vitro dissolution, and in vivo pharmacokinetic evaluations of pazopanib tablets

Pazopanib is an important agent in the era of targeted cancer therapy, particularly for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. In this study, we evaluated the quality of two different formulations using in vitro and in vivo methods. The wet granulation method was used to prepare 240402S-1 and 240402S-2 tablets. In vitro dissolution profiles of 240402S-1 and 240402S-2 tablets were determined using the paddle method, and their in vivo pharmacokinetic characteristics were assessed by establishing a beagle dog model. Two batches of pazopanib tablets (240402S-1 and 240402S-2) were successfully prepared. Based on the in vitro cumulative dissolution profiles, 240402S-2 tablet exhibited superior dissolution in a pH 3.0 medium, whereas 240402S-1 tablet was higher in media with pH 4.5 with 0.75% sodium dodecyl sulfate (SDS), and pH 6.8 with 1.0% SDS. In vivo pharmacokinetic study revealed that the 240402S-1 tablet exhibited significantly different terminal half-life ( t 1/2z ) and maximum plasma concentration ( C max ) values compared with the reference tablet, with a statistically significant difference (P < 0.05). In contrast, the 240402S-2 tablet demonstrated population bioequivalence with respect to the reference tablet. In summary, the 240402S-2 tablet is recommended for further development. The analytical method established in this study can be applied in subsequent optimization studies, thereby improving efficiency and costs. • Two batches of pazopanib tablets have been successfully prepared and are ready for further optimization for clinical use. • The combination of in vivo pharmacokinetics and in vitro dissolution experiment was used to comprehensively evaluate the quality of pazopanib. • UHPLC-MS/MS method can provide an important tool for preclinical and clinical studies of pazopanib in biological samples.