CRYSTENGCOMM
·
2021
·Vol. 23
·期 46
·8027-8032
·
IF 3.545
Fenghua Chen,Jie Fan,Xiuzhi Chen,Yanping Li,Chengfeng Liang,Shizhao Ren,Rongrong Xue
Polymorph control of 5-fluorouracil (5-FU) was achieved by ball milling. Form II was synthesized through one-step neat grinding of raw 5-FU (RFU), and Form III (a new polymorph) was obtained by neat grinding RFU twice. Forms II and III of 5-FU were prepared separately through ball milling with different amounts of ethanol as an additive at the same period without influencing each other.
研究领域:
药物化学
·
制药工程
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产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2022
·
IF 4.01
Shuqi Lu,Kaxi Yu,Shuping Wang,Jiyong Liu,Shuna Liu,Xiurong Hu,Guping Tang
Lenvatinib is a cancer treatment drug approved by the U.S. Food and Drug Administration, which is a multitarget tyrosinase inhibitor. The commercially available form is its mesylate. In this work, five lenvatinib mesylate (LEM) solid-state forms, including two polymorphs (LEM-A, LEM-C) and three pseudopolymorphs (a hydrate (LEM-H) and two iso-structural solvates (LEM-H-EA and LEM-H-THF)), were prepared and characterized using various methods. Powder diffractions of LEM-A and LEM-C have been reported, but their crystal structures were reported for the first time by us. Hydrate and two iso-structural solvates were also first prepared and characterized by thermal analysis, X-ray diffraction, and so forth. The mutual transformation of different forms was studied. Two solvates easily lost their solvent and turned into LEM-B, which provided the possibility for the preparation of LEM-B. In addition, thermal stability and solubility of LEM-A, LEM-C, and LEM-H were determined, along with the respective molecular conformation, their inter- and intramolecular interactions, and packing arrangements.
研究领域:
药物化学
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晶体学
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药剂学
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Shuting Li,Binbin Liu,Ziqiao Chen,Xiao Ou,Haowei Rong,Ming Lu
Identification of a thermodynamically stable polymorph is an important step in the early stage of drug development. Ritonavir (RIT) is a well-known case where the most stable polymorph II emerged after being marketed, leading to a loss of $250 million. Herein, we report the findings that routine melt crystallization can reveal the late-appearing polymorph II of RIT at small supercooling, but the probability of nucleation is very low. The addition of 30–50% polyethylene glycol (PEG) promotes the crystallization of Form II as the only phase at low supercooling, making it easier to detect in polymorphism screening. During the course of our research, a new polymorph, denoted Form III, was unexpectedly discovered, crystallizing as the major phase from neat RIT melts. Single crystals of Form III were grown from melt microdroplets. Benefiting from the ability of synchrotron radiation to detect weak diffraction signals that cannot be accessible by a laboratory diffractometer, a reasonable structure of Form III was solved with slight disorder relative to thiazole groups (P1 space group and Z′ = 4). The thermodynamic stability ranking of the three true polymorphs is Form II > Form I > Form III, as opposed to the order of solubility. The capacity to efficiently reveal rich polymorphs, especially the kinetically hindered polymorph, and rapidly grow single crystals of a new phase for structure determination together highlights the necessity of incorporating melt crystallization into routine methods for pharmaceutical polymorphism screening.
研究领域:
药学
·
材料科学
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晶体学
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产品关联
DOI
PubMed
高影响因子
AICHE JOURNAL
·
2023
·
IF 3.7
Tuo Yao,Jian Liu,Xuxing Wan,Beibei Li,Sohrab Rohani,Zhenguo Gao,Junbo Gong
In situ monitoring and closed-loop control of the solution crystallization process are the modern trends for pharmaceutical development, in which the critical process parameters (CPPs) as well as the product critical quality attributes (CQAs) can be regulated and guaranteed during the manufacturing process. In this study, an in situ image monitoring methodology based on a state-of-the-art deep-learning model was developed to track the CQAs such as polymorph ratio, two-dimensional crystal size, and crystal shape in a solvent-mediated polymorphic transformation (SMPT) process. Coupled with the multidimensional process information, a 2D population balance model (PBM) was developed and validated using the results of the in situ image-based CQAs analysis. The 2D-PBM was solved using a high-resolution finite volume method (HR-FVM) which could provide a high dimensional particle-size distribution. Through the validation between the process image analysis and the 2D-PBM, the accuracy of image analysis was discussed, and the potential and challenges of in situ image analysis were proposed. This work aims to integrate the crystal polymorphism and two-dimensional crystal size distribution (2D-CSD) information in the SMPT process using intelligent microscopic image analysis and then to validate the results of neural network processing by solving the numerical solution of the multidimensional PBM.
研究领域:
制药工程
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化学工程
·
人工智能应用
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产品关联
DOI
高影响因子
JOURNAL OF CRYSTAL GROWTH
·
2019
·
IF 1.573
Bo Zhang,Xiaxu Hou,Leping Dang,Hongyuan Wei
A screening method for selective polymorphic crystal growth was proposed using molecular modeling as an assistant tool in this work. Three typical pharmaceutical polymorphic crystals which are theophylline , l -serine and fumaric acid were chosen as case studies to investigate their selective growth on self-assembled monolayer (SAM) prepared by depositing 3-mercaptopropionic acid (MPA) on gold. Molecular modeling was applied to analyze the arrangement of MPA molecules on the surface, as well as to value the binding energy between these three crystal faces with MPA SAM. The simulation results were used to predict the effect of SAM on the two dimensional selective growth of the polymorphic crystals, and crystallization experiments were carried out to verify the modeling prediction. The results indicate that MPA SAM can directionally induce the nucleation of polymorphic crystals by geometric and chemical interactions matching. Molecular modeling can be as an effective assistant tool to reveal the matching degree, which can give valuable suggestions on the polymorphic drug design.
研究领域:
药物结晶学
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分子药剂学
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计算化学
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表面科学
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晶体工程
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药物多晶型
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DOI
高影响因子
JOURNAL OF SOLID STATE CHEMISTRY
·
2023
·
IF 3.3
Jia Luo,Yuqing Luo,Jun Tan,Hongsheng Che,Ting He,Jiugang Hu
The large-scale and controllable production of boehmite has attached much attention due to its extensive application in advanced energy and electronics industries. In this study, a facile vaporthermal (VPH) method was developed for the rapid fabrication of rhombic boehmite microflakes using low-cost commercial gibbsite particles. The evolution behaviors of gibbsite to boehmite under VPH and conventional hydrothermal (LPH) conditions were ex-situ monitored by XRD , Raman, and FT-IR techniques. The boehmite powders from VPH (V-boehmite) and LPH (L-boehmite) have similar crystal structure and bonding vibration information, whereas V-boehmite exhibits rhombic morphology and L-boehmite presents cubic morphology. Moreover, the formation time of boehmite can be shortened from 16 h of LPH to 6 h of VPH at 180 °C, which significantly contributes to its scalable production. These differences of V-boehmite are attributed to the direct contact between high-temperature saturated water steam and gibbsite, which can induce the rapid formation of rhombic boehmite microflakes through dissolution-recrystallization mechanism. Therefore, the vaporthermal technology has great potential for efficient, sustainable, and large-scale production of boehmite powders.
研究领域:
材料科学
·
能源技术
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产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2025
·
IF 3.4
Guiyu Chen,Pengpeng Yang,Mengyang Cai,Keke Zhang
Strategically modifying functional groups on pore surfaces of confined materials offers an effective approach to regulating crystal nucleation and growth, which is significant for polymorphic pharmaceuticals. Using isonicotinamide (INA) as a model polymorphic compound, this study systematically investigates the effects of pore surface chemistry─engineered with –CH3, –OH, –COOH, and –NH2 groups─on polymorph selection under nanoconfinement. The results reveal distinct pathways: hydroxyl-functionalized pores exclusively yield metastable form VI, methyl-functionalized pores predominantly yield form II, while amine- and carboxyl-functionalized pores yield mixed form II/VI. The OH-modified system demonstrates selectivity for form VI, attributed to specific OH···INA hydrogen-bonding interactions that significantly reduce its nucleation activation energy. This study aims to establish a selective synthesis methodology for polymorphic control of isonicotinamide through spatial confinement and surface chemistry modulation, ultimately achieving high-purity form VI and form II. These findings establish a novel approach for controlling polymorphic outcomes via the rational design of confinement surface chemistry.
研究领域:
药物晶体学
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材料化学
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纳米材料
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物理化学
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多晶现象
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产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Tingyu Yang,Jilagamazhi Fu,Liang Ma,Hong Du,Xiaoqing Yue,Bosheng Zhao,Cuiyan Wang
In biomineralization, organisms have the abilities to produce biominerals with superior properties. One of the most attractive features of biominerals is the presence of the proteins consisting of different contents of amino acids in crystals. In the present work, L-phenylalanine (Phe) was used as an additive for the controllable crystallization of calcium carbonate (CaCO 3 ). The obtained CaCO 3 crystals were characterized by field emission scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), elemental analysis and high-resolution transmission electron microscopy (HRTEM). The experimental results suggest that single calcite crystals are formed at low Phe concentrations. High concentrations of Phe inhibit the nucleation and growth of calcite, and promote the formation of vaterite crystals with solid or hollow structures. The morphology and crystal form of CaCO 3 are also significantly affected by the flow rate of CO 2 . After that, a possible mechanism (competition mechanism) action of Phe in the formation of CaCO 3 is proposed. Finally, the effects of temperature on the formation of vaterite were determined to explore the growth mechanism of hexagonal vaterite. The work of controlling the preparation of CaCO 3 crystals in the presence of Phe will help us to imitate and learn nature, and bring new insights into understanding bionics. Meanwhile, it provides a new method for the synthesis of CaCO 3 biomaterials with different crystal forms and morphologies.
研究领域:
材料科学
·
生物矿化
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DOI
高影响因子
Crystals
·
2019
·Vol. 9
·期 5
·260
·
IF 2.061
Manli Zhu,Yongli Wang,Fei Li,Ying Bao,Xin Huang,Huanhuan Shi,Hongxun Hao
In this work, theophylline was selected as the model compound to study and simulate the solution-mediated polymorphic transformation. The polymorph I and polymorph II of theophylline were prepared and fully characterized. Raman and UV spectra methods were carried out to observe the phase transformation of theophylline from polymorph I to polymorph II at different temperatures. The theoretical models, including dissolution model, nucleation model, and growth model, were established to describe and simulate the transformation processes. By combination of experiments and simulations, the controlling steps of the transformation processes were discussed. The effects of temperature and/or solvent on the transformation processes were evaluated. This work can shed light on the polymorphic transformation processes.Keywords:theophylline;polymorphic transformation;temperature;solvent;mathematical model
研究领域:
药学
·
化学
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DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2013
·
IF 2.206
Chongjun Liu,Leping Dang,Yao Tong,Hongyuan Wei
In this paper, the influence of polymorphs on the transformation water activity that corresponds to the transformation between hydrate and anhydrate of theophylline was investigated. Theophylline is known to exist either as anhydrates or a monohydrate. The transformation water activities of theophylline form II and IV were determined respectively, and the solubility data of these two forms in methanol, ethanol, acetonitrile, and acetone was also determined. The following thermodynamic derivation indicates that the transformation water activity ratio of theophylline forms II to IV can be correlated with the solubility ratio. According to the above study, the stability and intercoversion of theophylline polymorphs is discussed. This work will be useful in understanding the transformation process and benificial for industrial process control.
研究领域:
药学
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物理化学
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DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2024
·
IF 3.2
Ronghua Peng,Xueyou Qin,Jiawei Lin,Lingyu Wang,Songgu Wu,Junbo Gong
We designed a solvent mixture composed of carboxylic acid solvents and water as the crystallization medium for the selective preparation of three distinct γ-aminobutyric acid (GABA) conformational polymorphs (Form-I, Form-II, and the newly discovered Form-IV). By adjusting the carbon chain length and content of carboxylic acid solvents, we were able to finely tune the solvation environment, leading to the formation of the desired polymorphs. Crash-cooling crystallization experiments demonstrated that with the carbon chain length (C1–C6) and content (0–30%) of carboxylic acid increasing, the polymorphic outcomes gradually change from Form-I to Form-II and ultimately to Form-IV. Interestingly, four different conformations were observed within these three polymorphs. DFT calculation indicated that the stability order of these conformations is conformer-IVβ > conformer-IVα > conformer-II > conformer-I. Based on solution FTIR analysis and solvation free energy calculation, the solvation effect on GABA molecules diminishes with an increasing carbon chain length and content of carboxylic acid solvents. A lower solvation effect makes the desolvation process of GABA molecules much easier so that GABA molecules can undergo sufficient conformational rearrangement during the nucleation stage, thereby adopting a more stable conformation during the molecular assembly process. In this crystallization conditions, Form-IV with a more stable conformation in its crystal structure has the potential to replace Form-II and Form-I through preferential crystallization.
研究领域:
化学
·
材料科学
·
药物学
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产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 1
·449
·
IF 4.6
Canran Wang,Shan Jiang,Wenyue Ma,Zhaoyang Liu,Leijing Liu,Yongcun Zou,Bin Xu,Wenjing Tian
Radioactive iodine-capturing materials are urgently needed for the emerging challenges in nuclear waste disposal. The various pore structures of covalent organic frameworks (COFs) render them promising candidates for efficient iodine adsorption. However, the detailed structure–property relationship of COFs in iodine adsorption remains elusive. Herein, two polymorphic COFs with significantly different crystalline structures are obtained based on the same building blocks with varied molecular ratios. The two COFs both have high crystallinity, high specific surface area, and excellent chemical and thermal stability. Compared with the [C4+C4] topology (PyT-2) with an AA stacking form, the [C4+C2] topology (PyT-1) with an AB stacking form has more twisted pore channels and complex ink-bottle pores. At ambient conditions, PyT-1 and PyT-2 both exhibit good adsorption properties for iodine capture either in a gaseous or liquid medium. Remarkably, PyT-1 presents an excellent maximum adsorption capacity (0.635 g g−1), and the adsorption limit of PyT-2 is 0.445 g g−1in ann-hexane solution with an iodine concentration of 400 mg L−1, which is highly comparable to the state-of-the-art iodine absorption performance. This study provides a guide for the future molecular design strategy toward novel iodine adsorbents.Keywords:covalent organic framework;polymorphism;iodine adsorption
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）