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

卢燕; 丛逢; 钱帅; 魏元锋; 张建军; 林以宁; 高缘

doi:10.11665/j.issn.1000-5048.20210106

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

1.
中国药科大学中药学院，南京 211198
2.
中国药科大学药学院，南京 211198

基金项目: 国家自然科学基金资助项目(No.81703712，No.81773675，No.81873012)；中国药科大学“双一流”建设资助项目(No.CPU2018GY11，No.CPU2018GY27)

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出版历程
- 收稿日期: 2020-08-09
- 修回日期: 2020-12-07
- 刊出日期: 2021-02-24

Enhanced dissolution and eliminated gelation of lenvatinib mesylate by coamorphous system

1.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198
2.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81703712, No.81773675, No.81873012) and the Double First-Class Project of China Pharmaceutical University (No.CPU2018GY11, No.CPU2018GY27)

摘要

摘要: 甲磺酸乐伐替尼（LF）是一种多靶点酪氨酸酶抑制剂，主要用于治疗多种肿瘤。因其溶出过程中发生凝胶化而导致溶出度下降，生物利用度低。本研究通过旋蒸法制得甲磺酸乐伐替尼-黄芩素（LF-BAI）共无定形物（物质的量比为1∶1），以提高LF溶出度的同时消除其凝胶化。利用偏光显微观察、粉末X射线衍射法、差示扫描量热法、傅里叶变换红外光谱等手段进行表征，结果表明，共旋蒸产物为单相的共无定形物（T_g=118 ℃）。溶出试验发现LF-BAI共无定形可有效地消除LF在溶出过程中的凝胶化，且与LF晶体、BAI晶体相比，LF和BAI的溶出速率分别提高了2.2倍和25.4倍。稳定性试验表明，LF-BAI共无定形物在25 ℃/60%RH和40 ℃/75%RH条件下稳定至少90 d，表现出良好的物理稳定性。
- 甲磺酸乐伐替尼 /
- 黄芩素 /
- 共无定形 /
- 凝胶化 /
- 溶出度 /
- 稳定性
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 T_g 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.
- lenvatinib mesylate /
- baicalein /
- coamorphous /
- gelation /
- dissolution /
- stability

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