Crystals
·
2022
·Vol. 12
·期 12
·1722
·
IF 2.67
Yujiang Xie,Genpei Shi,Jie Sun,Si Li,Wei Gao,Yimin Hu,Chang Zu,Weiwei Tang,Junbo Gong
Developing multicomponent crystal forms, especially cocrystals and salts, is becoming a promising pathway to improve the solubility and bioavailability of drugs. Herein, new multicomponent crystals of SHR0302, a new generation of Janus Kinase (JAK) inhibitor that suffers from poor solubility, were developed based on a cooperative approach of computational and experimental coformer screenings. Virtual screening methods, including the conductor-like screening model for realistic solvents (COSMO-RS) and molecular complementary (MC) analysis, were employed to predict the binding affinity between SHR0302 and selected coformers. The developed screening method was capable of reducing the screening database to 30 coformers from a total of 42 proposed coformers. The proof-of-concept experimental screening study was performed to demonstrate the efficiency of computational screening, wherein three new multicomponent crystalline forms were found and fully characterized by powder X-ray diffraction, thermal analysis, and IR and1H-NMR spectroscopy. Further, the measurements of the solubility property of these new multicomponent crystal forms reveal an apparent promotion compared with the drug alone. Finally, the receiver operator characteristic (ROC) curve was used to assess the prediction performance of the COSMO-RS model. It was found that the established screening model can effectively shorten the experimental screening time and efforts.Keywords:multicomponent crystals;cocrystals;COSMO-RS;cocrystal prediction;solubility enhancement
研究领域:
药物化学
·
计算化学
✓ 已验证
产品关联
DOI
高影响因子
IUCrJ
·
2021
·
IF 4.769
Yanming Xia,Yuanfeng Wei,Hui Chen,Shuai Qian,Jianjun Zhang,Yuan Gao
Recently, cocrystallization has been widely employed to tailor physicochemical properties of drugs in the pharmaceutical field. In this study, cocrystallization was applied to separate natural compounds with similar structures. Three flavonoids [baicalein (BAI), quercetin (QUE) and myricetin (MYR)] were used as model compounds. The coformer caffeine (CAF) could form cocrystals with all three flavonoids, namely BAI-CAF (cocrystal 1), QUE-CAF (cocrystal 2) and MYR-CAF (cocrystal 3). After adding CAF to methanol solution containing MYR and QUE (or QUE and BAI), cocrystal 3 (or cocrystal 2) preferentially formed rather than cocrystal 2 (or cocrystal 1), indicating that flavonoid separation could be achieved by competitive cocrystallization. After co-mixing the slurry of two flavonoids with CAF followed by centrifugation, the resolution ratio that could be achieved was 70-80% with purity >90%. Among the three cocrystals, cocrystal 3 showed the lowest formation constant with a negative Gibbs free energy of nucleation and the highest energy gap. Hirshfeld surface analysis and density of states analysis found that cocrystal 3 had the highest strong interaction contribution and the closest electronic density, respectively, followed by cocrystal 2 and cocrystal 1, suggesting CAF could competitively form a cocrystal with MYR much more easily than QUE and BAI. Cocrystallization is a promising approach for green and effective separation of natural products with similar chemical structures.
研究领域:
药物化学
·
天然产物化学
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DOI
PubMed
高影响因子
THIN SOLID FILMS
·
2019
·
IF 1.888
Jian He,Aisen Li,Yanchun Tao,Ning Chu,Zhixiang Wang,Shuping Xu,Jing Wang,Houyu Zhang,Jingsheng Yu,Weiqing Xu
A two-dimensional (2D) co-crystal composed of 1, 3, 5-trifluoro-2, 4, 6-triiodobenzene and 4, 4′-trimethylenedipyridine via halogen bonding (I···N) was obtained on highly-oriented pyrolytic graphite , and was characterized by scanning tunnelling microscope supplemented by the density functional theory calculation. Its special structure at the interface was further compared with its three-dimensional (3D) co-crystal structure. No orderly structures were observed when Au (111) was applied. The 2D co-crystal grown on the interface is significantly different from the 3D co-crystal. This study is of vital significance in understanding the growth mechanisms of 2D functional co-crystals.
研究领域:
材料科学
·
化学
✓ 已验证
产品关联
DOI
高影响因子
Crystals
·
2019
·Vol. 9
·期 7
·329
·
IF 2.061
Yaohui Huang,Ling Zhou,Wenchao Yang,Yang Li,Yongfan Yang,Zaixiang Zhang,Chang Wang,Xia Zhang,Qiuxiang Yin
Pure theophylline-benzoic acid cocrystal was prepared via slurry and cooling crystallization in solution to overcome the disadvantages of existing preparation methods. The target cocrystal was characterized by powder X-ray diffraction (PXRD), thermalgravimetric analysis (TGA), differential scanning calorimetry (DSC) and Raman spectroscopy. The slurry and cooling cocrystallization process in solution was monitored via on-line Raman spectroscopy. The results obtained from on-line Raman monitoring can exhibit the transformation process from raw materials (theophylline and benzoic acid) to cocrystal and show the cocrystal formation rate. Comparing each transformation process under different conditions in slurry crystallization, we found that suspension density of raw materials and temperature both have an impact on the theophylline-benzoic acid cocrystal formation rate. It could be concluded that the cocrystal formation rate increased with the increase of suspension density of raw materials. Further under the same suspension density, higher temperature will accelerate theophylline-benzoic acid cocrystal formation. Meanwhile, various data from the cocrystallization process in cooling crystallization, including nucleation time, nucleation temperature and suitable cooling ending point can be gained from results of on-line Raman monitoring.Keywords:cocrystal;solution crystallization;Raman spectroscopy;on-line monitoring;cocrystal formation
研究领域:
药学
·
分析化学
✓ 已验证
DOI
高影响因子
Small
·
2025
·
IF 12.1
Xia Wang,Zongwei Guo,Guihua Yang,Xingxiang Ji,Gaojin Lyu
Eutectogels have garnered attractive interest for applications in electrochemistry, environmental science, energy storage, and flexible sensing. Emerging flexible temperature sensors demand materials with high environmental stability, robust adhesion, superior mechanical properties, certain self-healing capacities, and good transparency. Herein, deep eutectic solvent (DES), composed of acrylic acid and guanidine hydrochloride, is combined with catechol and mesoporous molecular sieves to construct a dynamic network of multiple hydrogen bonds, resulting in multifunctional gels. The eutectogel demonstrated exceptional stretchability (1680.4%, 178.12 kPa), compressive strength (70%, 760.9 kPa), fatigue resistance (no significant deviation for 10 cycles), adhesion strength (35.8 kPa), transparency (92.41%), and UV-blocking capabilities. The non-volatile nature of the DES and the formation of hydrogen bonds during crosslinking preserved the DES within the gel, enhancing its moisture retention (weight change ratio of ≈2% after 6 days). Additionally, the freezing point of gel is effectively lowered, improving its environmental stability (−70–50 °C). Based on the aforementioned characteristics, the eutectogel is applied in the field of electrocardiogram detection. This bioelectrode is capable of monitoring changes in human heart rate under extreme conditions and can be assembled with wearable devices to provide a promising solution for the diagnosis and prediction of cardiovascular disease.
研究领域:
生物医学工程
·
柔性电子
·
生物传感
·
材料科学
·
心血管监测
·
可穿戴设备
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Xiangjun Shi,Chao Wang,Qifeng Chen,Shuimei Shen,Shengjie Song,Xiyue Zhou
Ibrutinib(IBR) is an irreversible Bruton's tyrosine kinase inhibitor and has been classified as the Biopharmaceutical Classification System (BCS) class Ⅱ drug. The objective of the current study was to improve the physicochemical properties of IBR by co-crystallization. Based on ΔpKa analysis and structure analysis, we reported seven IBR pharmaceutical cocrystals with different structure types of co-formers such as hydroxy-2-naphthoic acids, mono-hydroxybenzoic acids, and aliphatic acids via the slurry method and ultrasonic method. The seven prepared cocrystals were characterized by powder X-ray diffraction(PXRD), differential scanning calorimetry(DSC), thermogravimetric analysis(TGA) and Fourier transform infrared spectroscopy(FT-IR). The solubility and accumulative dissolution of IBR cocrystals were explored. It was found that the solubility and dissolution were optimally increased up to 6.64 times and 1.85 times than that of IBR Form A, respectively. Moreover, all the IBR cocrystals maintained a stable cocrystal state after 90-d under 40 °C/75% RH condition and after 30-d under 60 °C/0% RH condition. According to the results analysis, there may be hydrogen bond(H-bond) and π-π stacking interactions in the IBR cocrystal system. The current study demonstrated that the co-crystallization of IBR with specific co-formers proposed a prospective technology and optional strategy to modify the physicochemical nature of IBR.
研究领域:
药学
·
化学
✓ 已验证
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2020
·
IF 4.089
Xin Chen,Duanxiu Li,Zongwu Deng,Hailu Zhang
Ketoconazole (KTZ) is an imidazole derivative that is used to treat a wide variety of fungal infections and other human diseases. As a class II compound in the biopharmaceutics classification system, KTZ has low aqueous solubility. To improve this disadvantage, five phenolic acids were employed to form cocrystals with KTZ. The antifungal and anti-inflammatory activity of the phenolic acids may bring an enhanced therapeutic effect and reduce the risk of hepatotoxicity at the same time. The structural information on these five crystalline samples and KTZ were fully disclosed by single-crystal X-ray diffraction. In addition to a previously reported carboxylic acid···imidazole N interaction, hydroxyl···imidazole N hydrogen bonding also appears in the KTZ cocrystals as a main supramolecular heterosynthon. The short strong hydrogen bonds were observed in two cocrystal structures, which contain slightly longer carboxylic O–H length. 15N solid-state NMR also provided valuable clues for the confirmation of the molecular/ionization states. The dissolution tests revealed that all the newly obtained cocrystals exhibit significantly improved solubility compared to KTZ.
研究领域:
药学
·
化学
✓ 已验证
DOI
高影响因子
ACS Sustainable Chemistry & Engineering
·
2022
·
IF 9.224
Jie Cheng,Hao Qin,Hongye Cheng,Zhen Song,Zhiwen Qi,Kai Sundmacher
As traditional methods for retrieving natural vitamin E suffer from harsh operating conditions and poor process performance, seeking more energy-efficient and sustainable alternative approaches is highly desirable. In this work, deep eutectic solvents (DESs) as a class of emerging media are particularly proposed for the extraction of vitamin E (modeled by α-tocopherol) from deodorized distillates under mild operating conditions. To select DESs suitable for this task, a rational screening method is presented which covers the thermodynamic evaluation of individual components and component combinations, the assessment of environment, health, and safety (EHS) impacts of components, and the eutectic behavior estimation of component combinations. Based on experimentally reported DESs from the literature, individual components as well as random combinations of potential hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) are successively prescreened by COSMO-RS predicted thermodynamic properties. Five EHS-related properties of HBDs are assessed by VEGA. The formation of eutectics and the corresponding operating window of different HBA–HBD combinations are estimated by COSMO-RS solid–liquid equilibria prediction. Experiments are finally performed with the top-ranked DESs, which well validates the reliability of the screening method and identifies tetrabutylphosphonium chloride–ethanolamine (2:1) as a suitable DES for the α-tocopherol extraction.
研究领域:
化学工程
·
绿色化学
·
溶剂科学
·
制药技术
✓ 已验证
产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2012
·
IF 4.72
Qian Tao,Jia-Mei Chen,Lei Ma,Tong-Bu Lu
One phenazopyridine monohydrate (1·H2O), one cocrystal of phenazopyridine with phthalimide (2), and three salts of phenazopyridine with benzoic acid (3), 4-hydroxyphenylacetic acid (4), and scaaharin (5) were synthesized, and their structures were determined by single crystal X-ray diffraction. The results of dissolution experiments indicate that the solubility of phenazopyridine can be enhanced after the formations of cocrystal and salts, in which the apparent solubility value of 5is approximately 9 times as large as that of phenazopyridine in water, and the apparent solubility value of 4 is approximately 10 times as large as that of phenazopyridine hydrochloride (1·HCl) in 0.1 M HCl aqueous solution. The results of the stability study demonstrate that 2–5 are less hygroscopic than 1·H2O and 1·HCl at both 85% and 98% RH.
研究领域:
药学
·
化学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2016
·
IF 1.78
Yanlei Kang,Jianming Gu,Xiurong Hu
Febuxostat was investigated due to its significant effect in the treatment of gout. However, its poor water solubility hinder its potential applications. In recent years, cocrystals have increasingly being applied to enhance the drug solubility . To improve the solubility, two cocrystals of Febuxostat were synthesized through the method of cooling crystallization. The prepared cocrystals febuxostat-isonicotinamide(FEB-INA) and febuxostat-arginine(FEB-Arg) were studied by microscopical observation, Powder X-Ray Diffraction(PXRD), Single Crystal X-ray Diffraction, Differential Scanning Calorimetry(DSC), and infrared spectrometry . At the same time, the cocrystals' solubility and dissolution rate were explored. Both the cocrystals showed higher solubility compared to the pure drug. The FEB-Arg cocrystal enhanced about 900 times of solubility compared to the pure drug. The current study proved that cocrystallization can be a better way to enhance the solubility of the poorly water-soluble drug.
研究领域:
药物化学
·
材料科学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 10
·4091
·
IF 4.6
Jia-Yao Chen,Xue-Wen Zhang,Tian-Yu Wu,Hai-Mu Ye
Crystalline/crystalline blends of polymer have shown advantages in the preparation of new polymeric materials. However, the regulation of co-crystallization in a blend is still full of challenges due to the preferential self-crystallization driven by thermodynamics. Here, an inclusion complex approach is proposed to facilitate the co-crystallization between crystalline polymers, because the crystallization process displays a prominent kinetics advantage when polymer chains are released from the inclusion complex. Poly(butylene succinate) (PBS), poly(butylene adipate) (PBA) and urea are chosen to form co-inclusion complexes, where PBS and PBA chains play as isolated guest molecules and urea molecules construct the host channel framework. The coalesced PBS/PBA blends are obtained by fast removing the urea framework and systematically investigated by differential scanning calorimetry, X-ray diffraction, proton nuclear magnetic resonance and Fourier transformation infrared spectrometry. It is demonstrated that PBA chains are co-crystallized into PBS extended-chain crystals in the coalesced blends, while such a phenomenon has not been detected in simply co-solution-blended samples. Though PBA chains could not be totally accommodated in the PBS extended-chain crystals, their co-crystallized content increases with the initial feeding ratio of PBA. Consequently, the melting point of the PBS extended-chain crystal gradually declines from 134.3 °C to 124.2 °C with an increasing PBA content. The PBA chains playing as defects mainly induce lattice expansion along thea-axis. In addition, when the co-crystals are soaked in tetrahydrofuran, some of the PBA chains are extracted out, leading to damage to the correlative PBS extended-chain crystals. This study shows that co-inclusion complexation with small molecules could be an effective way to promote co-crystallization behavior in polymer blends.Keywords:co-crystal;polyester;blend;inclusion complex;thermal property
研究领域:
材料科学
·
高分子化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2012
·
IF 4.72
Yan Yan,Jia-Mei Chen,Na Geng,Tong-Bu Lu
Four cocrystals of agomelatine with urea (1), glycolic acid (2), isonicotinamide (3), and methyl4-hydroxybenzoate (4) in 1:1 stoichiometry were successfully synthesized via six kinds of synthons. The structures of 1–4 were determined by the single crystal X-ray diffraction, in which 1–3 form two-dimensional hydrogen bonded frameworks between agomelatine and coformers, while 4 displays a one-dimensional chain structure. The results of differential scanning calorimetry measurements indicate that the melting points of 1–3 are between those of agomelatine and coformers, while the melting point of 4 is below those of agomelatine and coformer. After the formations of cocrystals, the solubility of agomelatine is much improved, and the solubility values of 1–4 in phosphate buffer of pH 6.8 are approximately 2.2, 2.9, 4.7, and 3.5 times as large as that of agomelatine Form II, and 1.6, 2.1, 3.4, and 2.5 times as large as that of agomelatine Form I. The solids of 1–4 can keep their crystalline forms in phosphate buffer of pH 6.8 for 3.5, 2.0, 6.0, and 15.0 h, respectively.
研究领域:
药学
·
晶体化学
·
药物化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）