INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Jiaquan Li,Yangjia Huang,Qi An,Wenyu Li,Jianting Li,Hongji Liu,Dezhi Yang,Yang Lu,Zhengzheng Zhou
Multi-component pharmaceutical systems such as cocrystal and salt have gained popularity in academia and industry due to their ability to regulate the poor physicochemical properties of active pharmaceutical ingredients (APIs). However, different crystal states, namely polymorphs are becoming a key factor influencing future clinical drug safety. It remains an under explored field, particularly how to hit the polymorphs of multi-components system quickly and effectively. For the first time, a novel drug-drug salt of lamotrigine (LAM)-tolfenamic acid (TOL) with two polymorphs and two solvates were discovered in this study. Forms I and II exist in rhombohedral and block crystal morphologies, whereas methanol and ethanol solvates are crystallized as rods and flakes, respectively. Further physicochemical properties were characterized and compared between parent compounds and the four crystal forms. The apparent solubilities of the new four crystal forms were higher than TOL but lower than LAM. The intrinsic dissolution rates of all crystal forms at 37.0 °C followed a similar trend, and all crystal forms were non-hygroscopic (<1.0%). Two stable polymorphs provide a new choice for the further formulation development.
研究领域:
药学
·
材料科学
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PubMed
高影响因子
CRYSTENGCOMM
·
2019
·Vol. 21
·期 35
·5284-5291
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IF 3.382
Xinyi Wang,Shijie Xu,Lina Jia,Yujia Yang,Yu Liu,Junbo Gong,Songgu Wu
The incorporation of drug–drug salts is known as an attractive strategy to not only improve physicochemical properties but also extend the field of combination drug delivery. Mefenamic acid (MFA) and tolfenamic acid (TFA) belong to effective but poorly soluble anti-inflammatory drugs used for treating both humans and animals. Piperazine (PPZ) has anthelmintic activities with a serious hygroscopic problem. To improve the physicochemical properties of such drugs and seek possible drug combinations, herein, four novel MFA\TFA–piperazine (PPZ) drug–drug salts with different stoichiometry (2 : 1 and 1 : 1) were designed and synthesized. As we expected, the experiments proved that their solubilities and dissolution properties were much better than that of MFA and TFA. Among them, the apparent solubility of the MFA–PPZ salt (1 : 1) improved about 130 times more than that of MFA in a mixture of water and ethanol. Meanwhile, these salts were non-hygroscopic based on dynamic vapor sorption analysis. Moreover, the obtained crystals were fully analyzed by single-crystal X-ray diffraction (SXRD), Hirshfeld surface analysis and a solvent mediated phase transformation study, which provided a better understanding of the crystal structure. The MFA–PPZ salt (2 : 1) and TFA–PPZ salt (2 : 1) possessed a similar crystal structure and their solubilities were also similar. In addition, the incorporation of PPZ in the crystal lattice destroyed the dimer form in the original MFA\TFA crystal and resulted in the formation of salts through a new ionic hydrogen bond. After contact with the solvents, PPZ was more likely to interact with the solvent molecules, which may have led to the acceleration of dissolution.
研究领域:
药学
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材料科学
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兽医学
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高影响因子
Theranostics
·
2024
·
IF 12.4
Kai Ni,Bo Che,Rong Gu,Chunhong Wang,Hongyang Xu,Huiduo Li,Shiyan Cen,Mingzhi Luo,Linhong Deng
Rationale: Bitter taste receptors (TAS2Rs) are abundantly expressed in airway smooth muscle cells (ASMCs), which have been recognized as promising targets for bitter agonists to initiate relaxation and thereby prevent excessive airway constriction as the main characteristic of asthma. However, due to the current lack of tested safe and potent agonists functioning at low effective concentrations, there has been no clinically approved TAS2R-based drug for bronchodilation in asthma therapy. This study thus aimed at exploring TAS2R agonists with bronchodilator potential by BitterDB database analysis and cell stiffness screening. Methods: Bitter compounds in the BitterDB database were retrieved and analyzed for their working subtype of TAS2R and effective concentration. Compounds activating TAS2R5, 10, and 14 at < 100 μM effective concentration were identified and subsequently screened by cell stiffness assay using optical magnetic twisting cytometry (OMTC) to identify the most potent to relax ASMCs. Then the compound identified was further characterized for efficacy on various aspects related to relaxation of ASMCs, incl. but not limited to traction force by Fourier transform traction force microscopy (FTTFM), [Ca 2+ ] i signaling by Fluo-4/AM intensity, cell migration by scratch wound healing, mRNA expression by qPCR, and protein expressing by ELISA. The compound identified was also compared to conventional β-agonist (isoproterenol and salbutamol) for efficacy in reducing cell stiffness of cultured ASMCs and airway resistance of ovalbumin-treated mice. Results: BitterDB analysis found 18 compounds activating TAS2R5, 10, and 14 at < 100 μM effective concentration. Cell stiffness screening of these compounds eventually identified flufenamic acid (FFA) as the most potent compound to rapidly reduce cell stiffness at 1 μM. The efficacy of FFA to relax ASMCs in vitro and abrogate airway resistance in vivo was equivalent to that of conventional β-agonists. The FFA-induced effect on ASMCs was mediated by TAS2R14 activation, endoplasmic reticulum Ca 2+ release, and large-conductance Ca 2+ -activated K + (BK Ca ) channel opening. FFA also attenuated lipopolysaccharide-induced inflammatory response in cultured ASMCs. Conclusions: FFA as a potent TAS2R14 agonist to relax ASMCs while suppressing cytokine release might be a favorite drug agent for further development of TAS2R-based novel dual functional medication for bronchodilation and anti-inflammation in asthma therapy.
研究领域:
药理学
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呼吸病学
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分子生物学
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Zhiyong Wu,Xinhao Wang,Lin Wang,Na Sun,Zihui Yang,Jianguo Zeng
Allocryptopine (ALL), a principal active component of the novel veterinary medicine Bopu Powder®, has gained widespread application in the poultry farming sector for the effective management of Escherichia coli ( E. coli ) diarrhea. In order to explore the metabolites and the pivotal enzymes associated with ALL, this study was conducted employing an in vitro chicken liver microsomal incubation. The metabolites of ALL were analyzed and identified by combining isotope tracing technology with the application of mass spectrometry fragmentation patterns. The key metabolic enzymes involved in the biotransformation of ALL were explored using the CYP450 recombinant enzyme method, which facilitated the identification of the enzymes contributing to ALL's metabolic pathway. The liver microsomal metabolism investigation revealed a total of five metabolites, with the predominant being M2 (harmol or 3-hydroxy-4-methoxy-6-methyl-5,7,8,15-tetrahydro-[1,3]dioxolo[4',5':4,5]benzo[1,2-g]benzo[c]azecin-14(6H)-one). The recombinant enzyme analysis conclusively identified CYP2D6 as the pivotal CYP450 isoenzyme that plays a central role in the metabolic pathway of the principal ALL metabolite, M2. This research not only expands our comprehension of the biotransformation process of ALL but also provides significant scientific evidence for the clinical safety of ALL, which was of great importance for guiding the application of ALL in the field of veterinary medicine.
研究领域:
兽医学
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药代动力学
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生物化学
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PubMed
高影响因子
ACS Sensors
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2025
·
IF 9.1
Lian Xu,Yan Xiao,Kun Yu,Hongshuo Pan,Jiayi Xu,Yiyun Guan,Mengke Wang,Xiangyu Xu,Hao Wang
The improper application of nonsteroidal anti-inflammatory drugs (NSAIDs) presents significant health hazards via vector food contamination. A critical limitation of these traditional existing approaches is their inability to concurrently discern and distinguish among diverse NSAIDs, presenting a notable gap in the analytical capabilities within this domain. Herein, a creative dual-channel fluorescence sensor array was developed for the rapid discrimination and determination of NSAIDs, utilizing complexes of cucurbit[8]uril (CB[8]) with three distinct modified poly(ethylenimines) (PEIs) to address this challenge. The array successfully differentiated and identified 19 NSAIDs with 97% accuracy at a concentration of 1 mM. In addition, it also achieved analyses of individual NSAIDs across a range of concentrations, NSAID mixtures, and impurities of aspirin using statistical analysis methods. More importantly, the approach effectively detected NSAIDs in complex matrices, such as milk and urine, demonstrating its potential for real-world applications.
研究领域:
分析化学
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食品安全
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药物检测
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PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2019
·Vol. 17
·期 13
·3409-3415
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IF 3.49
Xinyi Wang,Yifu Chen,Junbo Gong,Jinze Hou
Rare multiple fluorescence properties including aggregation-induced emission and polymorphism/shape/size-dependent emission were found coexisting in a class of typical non-steroidal anti-inflammatory analgesic drugs, fenamates, which could provide a new approach toward future drug evaluation. Different from the complexity and biological incompatibility of the traditional AIE molecular design, this work opens new avenues to the development of new AIE systems.
研究领域:
药理学
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材料科学
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生物医学工程
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PubMed
高影响因子
MICROCHIMICA ACTA
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2015
·Vol. 182
·期 15
·2585-2591
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IF 3.741
Luo Zhi-yuan,Li Zhi-yong,Liu Hai-yan,Tang Min-qiong,Shi Zhi-guo
Magnetic nanoparticles (MNPs), prepared via thiol-ene click chemistry and containing both diol and octadecyl groups, are shown to possess both hydrophobic and hydrophilic functionalities. They display excellent dispersibility in water and also are capable of extracting non-steroidal anti-inflammatory drugs (NSAIDs) from water samples. The MNPs can be magnetically separated, and the NSAIDs eluted with acetonitrile-water (9:1, v:v) and submitted to high performance liquid chromatographic analysis. Extraction variables, such as the kind of ion-pairing reagents, amount of MNPs, pH of sample solution, extraction and desorption time, volume of desorption solvent and salt addition, were optimized. Under optimum conditions, the method has a wide analytical range (from 5 to 800 ng∙mL‾ 1 ), good reproducibility with intra-day and inter-day relative standard deviations of <19.2 % (for n = 6), and low detection limits of 0.32 to 1.44 ng∙mL‾ 1 for water samples. The results demonstrate that the material possesses good water compatibility, thus warranting ease of operation and good reproducibility.
The water-dispersible C18/diol-Fe 3 O 4 MNPs were prepared via “Thiol-ene” click reaction. The material can be used as MSPE sorbent to extract non-steroidal anti-inflammatory drugs from river water. Satisfactory results were obtained with convenient operation and good reproducibility.
研究领域:
分析化学
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材料科学
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药物分析
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DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2017
·Vol. 409
·期 12
·3103-3113
·
IF 3.431
Xue Shu-Wen,Li Jing,Xu Li
Magnetic melamine-formaldehyde resin was prepared via water-in-oil emulsification approach by entrapping Fe 3 O 4 magnetic nanoparticles as the core. The preparation of the magnetic resin was optimized by investigating the amount of polyethylene glycol 20000 and Fe 3 O 4 nanoparticles, the concentration of the catalyst (hydrochloric acid), as well as the mechanical stirring rate. The prepared material was characteristic of excellent anion-exchange capacity, good water wettability, and proper magnetism. Its application was demonstrated by magnetic solid-phase extraction of nonsteroidal anti-inflammatory drugs coupled to high performance liquid chromatography-UV analysis. Under the optimal conditions, the proposed method showed broad linear range of 1–5000 ng mL –1 of milk and urine samples, satisfactory reproducibility with intra-day and inter-day relative standard deviations less than 12.4% and 9.7%, respectively, and low limits of detection of 0.2 ng mL –1 for the studied nonsteroidal anti-inflammatory drugs. The developed method was successfully used for the determination of the nonsteroidal anti-inflammatory drugs in spiked urine and milk samples. The magnetic melamine-formaldehyde resin was promising for the sample pretreatment of acidic analytes via anion-exchange interaction with convenient operation from complex sample matrix.
Magnetic solid-phase extraction based on melamine-formaldehyde resin
研究领域:
分析化学
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材料科学
·
药物分析
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DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 78
·74654-74661
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IF 3.289
Yuqing Li,Yanhua Sun,Jian Chen,Xiaohong Zhu,Hui Li,Shen Huang,Yuwei Hu,Qi Chen,Shian Zhong
Graphene oxide (GO) was introduced as a sacrificial material, for the first time, to fabricate a hollow molecularly imprinted polymer (HMIP) via Pickering emulsion polymerization. A stable oil-in-water Pickering emulsion was obtained, and the optimum pH values affecting the stability of the emulsion were investigated. After polymerization, GO was peeled off using ammonia solution (pH = 11) via ultrasonication, and substantial specific binding sites were exposed. The physical and chemical properties of the material were characterized and analyzed by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The equilibrium adsorption could be reached rapidly within 5 min, showing excellent adsorption efficiency, and the equilibrium adsorption capacity was 40.76 mg g−1 at 25 °C. The imprinting factor was about 2.62. The selective analysis indicated a high affinity and selectivity of HMIP toward template diclofenac over mefenamic acid and carbamazepine.
研究领域:
材料科学
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环境科学
·
分析化学
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DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2018
·
IF 2.196
Xinyi Wang,Dejiang Zhang,Shiyuan Liu,Yifu Chen,Lina Jia,Songgu Wu
The solubility of imatinib mesylate in nine monosolvents and two binary solvents was determined by the shaken flask method followed by UV composition analysis from 278.15 to 318.15 K at atmospheric pressure. The solubility increases with the increasing of temperature in all solvents we chose. Meanwhile, the dissolving capacity of imatinib mesylate ranks as methyl acetate < 2-propanol < acetonitrile < isobutanol < 1-butanol < tetrahydrofuran < 1-propanol < ethanol < methanol. The Apelblat model, λh equation, and nonrandom two-liquid (NRTL) model described the solubility data of imatinib mesylate in monosolvents; simultaneously, the Apelblat model, combined nearly ideal binary solvent/Redlich-Kister model, and NRTL model were employed in binary solvents. The results show a satisfactory correlation with the experimental data. Additionally, mixing thermodynamic properties of imatinib mesylate were calculated based on the NRTL model, which reveals the mixing process is spontaneous and exothermic.
研究领域:
药学
·
物理化学
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Xueping Quan,Bing Yan
Metal-organic framework (MOF) and covalent-organic framework (COF) hybrid materials can combine the unique properties of MOF and COF components, and their applications in fluorescence sensing have attracted more and more attention. Herein, ZIF-90 is grown on 3D-COF by a simple in situ growing method in which the 7-amino-4-methylcoumarin (AMC) is encapsulated in ZIF-90 to construct a fluorescent sensor. Chloroquine phosphate (CQP) can coordinate with Zn2+ to decompose the ZIF-90 and release AMC. At 365 nm excitation, the ratiometric fluorescence signal AMC/3D-COF (I430/I598) increases linearly with CQP in a linear range of 4 × 10–5 to 4 × 10–4 M in urine. Under 340 nm excitation, quantitative analysis of CQP in the serum (3 × 10–6 to 4 × 10–5 M) is based on the fluorescence intensity of Zn-CQP/3D-COF (I384/I598). In addition, AMC@ZIF-90/3D-COF (1) exhibits high anti-interference and selectivity in sensing of FA with a “turn off” mode, with a correlation range of 1 × 10–5 to 1 × 10–3 M. The fluorescence color changes triggered by CQP under different excitation conditions, and the different fluorescence responses caused by CQP make it a highly secure anticounterfeiting platform. The synthesized dye@MOF/COF hybrids not only provide a new way to integrate multiple emission to design fluorescent probes for differentiation detection but also offer ideas for the design of anticounterfeiting platforms.
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高影响因子
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