期刊
MOLECULES
卷 26, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/molecules26092677
关键词
drug– drug cocrystal; apixaban; quercetin; solubility; bioavailability
资金
- National Key R&D Program of China [2016YFC1000900]
- CAMS Innovation Fund for Medical Sciences [2017-I2M-1-010]
- National Science and Technology Major Project of China [2020-I2M-1-003]
Novel cocrystals composed of two antithrombotic drugs with poor solubility were developed in this study to improve their solubility, bioavailability, and stability. Compared to physical mixtures and individual drugs, the cocrystals showed significantly enhanced dissolution behavior and increased bioavailability. The study provides a novel approach to overcome the limitations of drug combinations.
Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx-Que (1:1) and Apx-Que-2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx-Que-2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx-Que was increased compared with the physical mixture and Apx, and Apx-Que remained stable in high temperature and illumination conditions. Therefore, a drug-drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据