Two new nilotinib polymorphs with solubility advantages prepared by the melt crystallization process

Nilotinib, a tyrosine kinase inhibitor of Bcr-Abl, is classified as a BCS IV drug with low solubility. Therefore, it is necessary to screen polymorphs with solubility advantages to enhance nilotinib bioavailability. In this study, two new polymorphs (form X and form Y) of nilotinib were prepared by melt crystallization. Notably, in the phos-phate buffer saline (pH 6.8), the solubility and dissolution rate of form X were increased up to 4.00 and 7.04 fold than form A, and the solubility and dissolution rate of form Y were increased up to 1.07 fold and 1.52 fold than form A, which could provide more options for formulation development of nilotinib. Form X was induced by polymers, and the impact of polymers on polymorphism selectivity and nucleation induction time was investi-gated, which could be related to the effect of carbonyl groups and steric conformation of polymers. Form Y was prepared by two-time melt crystallization. Moreover, the formation of form Y was influenced by the thermal history, which displayed complex behavior concerning the parent melting state. Generally speaking, this study developed two nilotinib polymorphs with advanced solubility and discussed the mechanism of nilotinib melting crystallization, which could be guidance for melt crystallization screening.

Automated summary

In this study, two new polymorphs (form X and form Y) of nilotinib were prepared by melt crystallization. The solubility and dissolution rate of form X were significantly increased compared to form A, and the solubility and dissolution rate of form Y were also improved. These findings provide more options for formulation development of nilotinib.