Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution

doi:10.1021/acs.cgd.8b00684

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物质量控制与固体化学研究中心

	Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution
	Zhu, Bin 2; Wang, Jian-Rong3 ; Zhang, Qi 3; Li, Meiqi 3,4; Guo, Chunyang 2; Ren, Guobin 1,2; Mei, Xuefeng3
刊名	CRYSTAL GROWTH & DESIGN
	2018-08
卷号	18 期号:8 页码:4701-4714
ISSN号	1528-7483
DOI	10.1021/acs.cgd.8b00684
文献子类	Article
英文摘要	Apatinib (APA) belongs to the targeted antineoplastic family of drugs by inhibiting the vascular endothelial cell growth factor receptor (VEGFR-2) of tyrosine kinase. APA encounters poor aqueous solubility problems, and its therapeutic dosage form, apatinib mesylate (ATM), is unstable and dissociates completely to APA in aqueous solution. Here, we synthesized and evaluated three new cocrystals of APA with adipic acid (APA + ADA), sebacic acid (APA + SEA), and D/L-mandelic acid (APA + D/L-MA), and four new salts with succinic acid (APA + SUA-H2O), salicylic acid (APA + SA), 1-hydroxy-2-naphthoic acid (APA + HNA), and saccharin (APA + SAC). All the solid forms were characterized by powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and dynamic vapor sorption. The molecular components and structures were confirmed by single crystal X-ray diffraction. APA + SEA is able to overcome the instability problem and has improved solubility compared with ATM. Hence, APA + SEA has the potential to be a superior candidate for this important drug.
资助项目	National Natural Science Foundation of China[21576080] ; National Natural Science Foundation of China[21776073] ; Youth Innovation Promotion Association of CAS[2016257] ; CAS Key Technology Talent Program[00000000] ; SANOFI-SIBS Scholarship[00000000]
WOS关键词	ACTIVE PHARMACEUTICAL INGREDIENTS ; PHYSICOCHEMICAL PROPERTIES ; CO-CRYSTALS ; SOLID-STATE ; DOSAGE FORM ; DISSOLUTION ; DESIGN ; BIOAVAILABILITY ; POLYMORPHISM ; ADVANTAGE
WOS研究方向	Chemistry ; Crystallography ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000440956100060
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279643]
专题	药物质量控制与固体化学研究中心
通讯作者	Ren, Guobin; Mei, Xuefeng
作者单位	1.East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China; 2.East China Univ Sci & Technol, Lab Pharmaceut Crystal Engn & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 3.Chinese Acad Sci, Pharmaceut Analyt & Solid State Chem Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Bin,Wang, Jian-Rong,Zhang, Qi,et al. Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution[J]. CRYSTAL GROWTH & DESIGN,2018,18(8):4701-4714.
APA	Zhu, Bin.,Wang, Jian-Rong.,Zhang, Qi.,Li, Meiqi.,Guo, Chunyang.,...&Mei, Xuefeng.(2018).Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution.CRYSTAL GROWTH & DESIGN,18(8),4701-4714.
MLA	Zhu, Bin,et al."Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution".CRYSTAL GROWTH & DESIGN 18.8(2018):4701-4714.