Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin
Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin
复制标题
达格列净-柠檬酸共晶表现出比达格列净更好的固态特性
DOI：
10.1016/j.ejps.2017.04.008
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发表时间：
2017-06-15
影响因子：
4.6
通讯作者：
Chen, Jia-Mei
中科院分区：
文献类型：
--
作者：
Deng, Jun-Hui;Lu, Tong-Bu;Chen, Jia-Mei
达格列净（DAP）是一种有效的和选择性的钠-葡萄糖协同转运蛋白-2抑制剂，用于治疗2型糖尿病。DAP丙二醇一水合物（DAP-PDO-H2O，1：1：1）是当前片剂产品中使用的固体形式，用于解决DAP游离形式的严重吸湿性问题。然而，DAP-PDO-H2O在暴露于高温时存在不稳定的问题，这使其成为非晶态。在这项工作中，我们报告了一个新的1：1之间的DAP和柠檬酸（DAP-CA）共晶的制备和评价。DAP-CA共晶体对高温和高相对湿度表现出上级稳定性，而不损害溶解和压片性能。因此，DAP-CA是开发具有改进性能的下一代DAP片剂产品的有前景的固体形式。
Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.