Cocrystals of Lenvatinib with Sulfamerazine and Salicylic Acid: Crystal Structure, Equilibrium Solubility, Stability Study, and Anti-Hepatoma Activity

共晶 化学 溶解度 差示扫描量热法 热重分析 核化学 有机化学 结晶学 氢键 分子 物理 热力学
作者
Minghuang Hong,Shijia Li,Weijie Ji,Ming‐Hui Qi,Guobin Ren
出处
期刊:Crystal Growth & Design [American Chemical Society]
卷期号:21 (7): 3714-3727 被引量:12
标识
DOI:10.1021/acs.cgd.1c00022
摘要

The purpose of this study was to investigate the effect of cocrystal formation of lenvatinib on the drug’s properties, including solubility, stability, and anti-hepatoma activity. Lenvatinib (LEN) is a multitargeted tyrosine kinase inhibitor with poor aqueous solubility. In this work, cocrystals of LEN with sulfamerazine and salicylic acid were synthesized via slurry reactive crystallization. The corresponding single crystals were obtained by a slow evaporation method. The crystal structures and intermolecular interactions were characterized by single-crystal X-ray diffraction techniques, Hirshfeld surface analysis, and molecular electrostatic potential analysis. These two cocrystals crystallized in the monoclinic space group, and the structures are maintained by hydrogen-bonding interactions. The synthesized cocrystals were further characterized by powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and proton nuclear magnetic resonance spectrometer techniques. The solubility of LEN cocrystals was determined in four dissolution media. The results demonstrated that both LEN cocrystals showed improved solubility compared to LEN free base. Stability studies through dynamic vapor sorption analysis, stress testing, and accelerated testing corroborated that the synthesized LEN cocrystals were stable and exhibited lower hygroscopicity than LEN free base and commercially available LEN mesylate. Moreover, the in vitro cytotoxicity assay showed a decreased IC50 value of the LEN–SMR cocrystal, suggesting improved anti-hepatoma activity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
乔哥儿发布了新的文献求助10
1秒前
王几几完成签到,获得积分10
1秒前
淡淡代玉发布了新的文献求助10
1秒前
yu发布了新的文献求助10
1秒前
1秒前
3秒前
3秒前
joseph应助半糖糖采纳,获得10
4秒前
席松发布了新的文献求助10
4秒前
乐乐应助欧欧拉格朗日采纳,获得10
4秒前
小L发布了新的文献求助10
5秒前
王几几发布了新的文献求助10
6秒前
zhouz完成签到,获得积分10
6秒前
星渊完成签到,获得积分10
8秒前
9秒前
10秒前
慢羊羊发布了新的文献求助10
10秒前
CipherSage应助yuany采纳,获得10
11秒前
Janisa完成签到,获得积分10
12秒前
cczltdy完成签到,获得积分10
13秒前
宋66发布了新的文献求助20
15秒前
hiyuz完成签到,获得积分10
15秒前
hhh完成签到 ,获得积分10
16秒前
归尘应助欧欧拉格朗日采纳,获得10
17秒前
席松完成签到,获得积分10
18秒前
卡卡西应助失忆的蝴蝶采纳,获得20
18秒前
water应助zheng能量采纳,获得10
20秒前
23秒前
英俊的铭应助hiyuz采纳,获得10
24秒前
25秒前
yuany发布了新的文献求助10
26秒前
乔乔兔应助严艾采纳,获得20
27秒前
abc发布了新的文献求助10
27秒前
干饭大王应助liuzhen采纳,获得10
29秒前
香蕉觅云应助吃吃采纳,获得10
29秒前
30秒前
30秒前
情怀应助叶叶叶采纳,获得10
32秒前
33秒前
33秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969917
求助须知:如何正确求助?哪些是违规求助? 3514626
关于积分的说明 11175060
捐赠科研通 3249928
什么是DOI,文献DOI怎么找? 1795165
邀请新用户注册赠送积分活动 875617
科研通“疑难数据库(出版商)”最低求助积分说明 804891