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
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天然产物化学
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DOI
PubMed
高影响因子
Crystals
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2020
·Vol. 10
·期 10
·922
·
IF 2.404
Xiao Juan Liu,Yang Zhang,Xue Zhong Wang
In situ ATR-FTIR spectroscopy and imaging and image analysis were applied to the study of the multicomponent co-crystallization process involvingS-valsartan and sacubitril in which LCZ696 crystals were formed. LCZ696 is a combination drug for use in heart failure that was approved by the FDA in 2015 following development by Novartis Pharmaceuticals. Though much work was reported on LCZ696 about its pharmacokinetic and pharmacodynamic effects in the evaluation and clinical testing, less attention was paid to study on the co-crystallization process. LCZ696 crystals have shown difficulties in filtration mainly due to the small particle size. In this work, LCZ696 crystals were prepared successfully byS-valsartan and sacubitril, and characterized by SEM, XRPD, TG-DSC and ATR-FTIR. ATR-FTIR and imaging and image analysis were used to monitoring solution concentration and investigating the co-crystallization mechanism. It revealed that the nucleation process was very slow compared with the transformation process, which is indication that the co-crystallization was controlled by nucleation. LCZ696 crystals are composed of very thin hexagonal plates, which seems indicating that LCZ696 crystals grow mainly in two size dimensions. Stirrer speed and crystal seeds were found to have noticeable effect on the induction time, transformation time and crystal size distribution. The Johnson-Mehl-Avrami equation was found to be able to describe the co-crystallization process.Keywords:S-valsartan and sacubitril co-crystallization;LCZ696;ATR-FTIR;On-line process imaging
研究领域:
药学
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材料科学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF STRUCTURAL CHEMISTRY
·
2023
·
IF 2.2
Shunye Yu,Yi Shui,Shuo Liu,Gan Huang,Canxiao Huang,Chunhui Geng,Lili Liu,Hongming Liu
Two co-crystalline compounds containing telluric acid and iodate, namely AIO 3 ·H 6 TeO 6 (A = Rb + , NH 4 + ), were investigated as potential nonlinear optical materials. They crystallize into isostructural and consist of isolated [IO 3 ] group and [H 6 TeO 6 ] molecule linked by hydrogen bonds and charge interactions of Rb + /NH 4 + . They show phase-matching second harmonic generation responses with moderate intensity of 1.2 × KDP (Rb + ) and 1.1 × KDP (NH 4 + ). They also possess large optical band gaps over 4.25 eV and can be easily grown from aqueous solutions. The local dipole moment calculations based on the structures of AIO 3 ·H 6 TeO 6 (A = K + , Rb + , NH 4 + ) series of compounds indicate that the change of A + cation in their structural frame causes a slight change in the arrangement directions of [IO 3 ] and [Te(OH) 6 ] groups, and further induces their SHG responses of different intensities at the macroscopic level.
研究领域:
材料科学
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光学
·
晶体学
✓ 已验证
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Su-Su Meng,Yue-Ming Yu,Fan-Zhi Bu,Cui-Wei Yan,Zhi-Yong Wu,Yan-Tuan Li
The current research leverages the structural features and property superiorities along with benefits in protecting cardiovascular system of gallic acid (GLC) and gentisic acid (HGA) to optimize in vitro/vivo peculiarities of cardiotonic drug milrinone (MIL) through developing a stratagem of cocrystallization-driven double-optimized ternary salt cocrystal. This strategy assembles MIL ternary salt cocrystal by shaping a cocrystallization moiety relying on noncovalent interplays with GLC to obtain permeability advancement and molding a salt segment via the salification of proton transfer between HGA and MIL molecules to facilitate solubility enhancement. While the ameliorative in vitro properties further modulate the in vivo pharmacokinetic behaviors, thus fulfilling a dual optimization of MIL’s biopharmaceutical characteristics on both in vitro and in vivo aspects. Along this line, the first MIL ternary salt cocrystal, viz., [HMIL+-GA–]-MIL-GLC-H2O (denoted as MTSC hereinafter), has been satisfactorily constructed and precisely structurally identified by diversified techniques. The single-crystal X-ray diffraction experiment validates that a molecular salt [HMIL+-GA–] species cocrystallizes with one neutral MIL, two GLC, and five solvent water molecules, among which the organic constituents compose laminated hydrogen bond networks, and then are self-assembled by water molecules to a 3D supramolecular structure. The unique structural feature and stacking pattern of MTSC make both the permeability and solubility be respectively enhanced by 9.69 times and 5.17- to 6.03-fold compared with the parent drug per se. The experimental outcomes are powerfully supported by associated calculations based on density functional theory. Intriguingly, these optimal in vitro physicochemical natures of MTSC have been potently converted into strengths of in vivo pharmacokinetics, showcasing the elevated drug plasma concentration, elongated half-life, alongside advanced bioavailability. Consequently, this presentation not just contributes a brand-new crystalline form with utility values, but ushers in a new dimension of ternary salt cocrystals for improving in vitro/vivo limitations of poor drug bioavailability.
研究领域:
药剂学
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药物化学
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药物递送
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生物药剂学
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材料科学
✓ 已验证
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
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2013
·
IF 4.689
Na Geng,Jia-Mei Chen,Zi-Jian Li,Long Jiang,Tong-Bu Lu
The cocrystals and salts of an antiallergic drug, tranilast, were synthesized to improve its solubility and photostability. Two tranilast cocrystals with urea (1) and nicotinamide (2), as well as two salts with cytosine (3) and sodium ion (4), were obtained and characterized by infrared spectra, thermogravimetric analyses, differential scanning calorimetry, and powder and single crystal X-ray diffractions. The results of single crystal structure analyses of 1–3 indicate that tranilast combines amide groups in coformers via R22(8) synthon, resulting in a 1:1 stoichiometry. The complexes showed advantages in terms of solubility and photostability in comparison to pure tranilast. The maximum solubility values of 1–3 in phosphate buffer of pH 6.8 are approximately 1.6, 1.9, and 2.0 times as large as that of tranilast, and the residual of tranilast is 79.5, 92.9, 88.5, 86.2, and 87.4% for tranilast and 1–4, respectively, under the fluorescent lamp irradiation for 96 h.
研究领域:
药物化学
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材料科学
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分析化学
✓ 已验证
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2019
·
IF 4.153
Zhen Li,Meiqi Li,Bo Peng,Bingqing Zhu,Jian-rong Wang,Xuefeng Mei
Diethylstilbestrol (DES), a synthetic nonsteroidal estrogen, has been prescribed for advanced breast cancer and prostate cancer. However, its poor compliance, reactive metabolite toxicity and hydrophobicity-induced drug accumulation has limited its applications. In this study, we aimed to modulate its dissolution rate and reduce reactive metabolites and drug accumulation through cocrystallization. Cocrystals of DES with isonicotinamide (INA), picolinamide (PIN), nicotinamide (NIA), urea (UREA), sarcosine (SAR), and flavone (FLA) were obtained. Different crystallization strategies result in cocrystal polymorphs for DES with INA and FLA. Intrinsic dissolution rate (IDR) characterizations in pH 2.0 buffer solution were conducted. Two assumptions (enhancing Cmax or prolonging Tmax) with the aim of improving compliance were put forward. On the basis of the IDR results (DES-NIA with a 1.5-fold increase in IDR and DES-2FLA-B with a 5.5-fold decrease in IDR) and the pharmacological activities of coformers (NIA and FLA with CYPs inhibition and UGTs stimulation effects), the pharmacokinetic behaviors of these two cocrystals were further researched. The 2-fold prolongation of Tmax in the PK profile DES-2FLA-B facilitated an improvement in compliance. In addition, the higher clearance rates and the potential to reduce oxidative metabolites in DES-2FLA-B help to decrease the drug accumulation and reduce the adverse effects of DES.
研究领域:
药学
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药理学
·
化学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 11
·2478
·
IF 6.525
Yihua Jiang,Yinxiang Cheng,Mengyuan Xia,Bingrui Zhang,Qiaoce Ding,Liye Lu,Jian-Rong Wang,Xuefeng Mei
Dehydroepiandrosterone (DHEA) is an FDA-approved food supplement used as an assisted reproductive sex hormone. The bioavailability is severely limited by its poor solubility (23 µg/mL). Herein, we aimed to modulate its solubility through cocrystallization. Eight cocrystals of DHEA with pyrocatechol (CAT), hydroquinone (HQ), resorcinol (RES), phloroglucinol (PG), 1,5-dihydroxy naphthalene (DHN), p-hydroxybenzoic acid (PHBA), gallic acid (GA), and 5-hydroxyisophthalic acid (5HIPA) were designed and synthesized. Some basic characterization tools, including powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and Fourier transform infrared spectroscopy, were also applied in our work for basic analyses of cocrystals. It is indicated that DHEA-GA exhibits its superiority in dissolution and pharmacokinetic behaviors. While the area under the curve values of DHEA-GA is improved at the ratio of 2.2, the corresponding bioavailability of DHEA is expected to be accordingly increased.Keywords:DHEA;cocrystallization;crystal structure;solubility;bioavailability
研究领域:
药学
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材料科学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2022
·
IF 4.01
Yuehua Deng,Yuchen Chen,Fang Xie,Jingwen Tang,Rui Zhang,Huaiyu Yang,Yanbin Jiang,Shiyuan Liu
Screening of co-formers for a specific active pharmaceutical ingredient is challenging during the development of multi-component crystals. Taking minoxidil (MIN) as a model drug, this study aims to examine the predictivity of the Cambridge Structural Database (CSD), Hansen solubility parameter (HSP), and the conductor-like screening model for real solvents (COSMO-RS) methods. First, CSD analysis based on a supramolecular approach was employed. Then, HSP and COSMO-RS methods were used to predict the cocrystallization possibility between MIN and 27 co-formers, where 10 candidate cases were reported. Based on the predicted results, eight aromatic carboxylic acids formed new solid forms with MIN experimentally, which met the criteria of Δδt < 7 MPa0.5 and ΔHex < −2.00 kcal mol–1, respectively, and four single crystals of these were successfully obtained. Single-crystal X-ray diffraction and Hirshfeld surface analysis indicated that the proton transferred from co-formers to MIN, and seven new MIN multi-component crystals showed rapid release in the first 30 min (1.52- to 2.91-fold) with improved solubility. This study confirms the efficiency of the CSD method and demonstrates that the COSMO-RS method performs much better than the HSP method.
研究领域:
药学
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晶体学
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材料科学
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）