Enhanced dissolution and eliminated gelation of lenvatinib mesylate by coamorphous system

VernacularTitle:共无定形体系提高甲磺酸乐伐替尼的溶出度及消除其凝胶化研究
Author: Yan LU ¹ ; Feng CONG ; Shuai QIAN ; Yuanfeng WEI ; Jianjun Yuanfeng ; Yining LIN ; Yuan GAO
Author Information

1. 中国药科大学中药学院
Publication Type:Journal Article
Keywords: lenvatinib mesylate; baicalein; coamorphous; gelation; dissolution; stability
From: Journal of China Pharmaceutical University 2021;52(1):44-51
CountryChina
Language:Chinese
Abstract: Lenvatinib mesylate (LF), a multi-target tyrosinase inhibitor mainly used in the treatment of a variety of cancers, has low oral bioavailability mainly due to its gelation during the dissolution process. In the current study, in order to enhance dissolution and eliminate gelation of LF, a supramolecular coamorphous system of LF-baicalein (BAI) (molar ratio, 1∶1) was prepared by rotary evaporation and characterized by PLM, PXRD, DSC and FTIR. Results indicated the formation of coamorphous system with a single Tg of 118 °C. Different from original LF crystal, no gelation phenomenon was observed during the dissolution of coamorphous LF-BAI. In addition, the dissolution rate of LF was increased by 2.2-fold after coamorphization. Meanwhile, the dissolution rate of the co-former BAI was also enhanced by more than 25.4-fold. Stability test showed that the prepared coamorphous system had a good physical stability for at least 90 days under 25 °C/ 60%RH and 40 °C /75%RH conditions.