JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2021
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IF 3.981
Hongji Liu,Hongqing Lin,Zhengzheng Zhou,Liang Li
Bergenin ( BER ) is a bioactive compound used for the treatment of chronic bronchitis in China. However, its low solubility and permeation limits its oral bioavailability. In this study, a new BER : isonicotinamide ( ISN ) cocrystal (1: 1, molar ratio) was reported for the first time. BER-ISN shows better solubility and intrinsic dissolution rates (IDRs) in aqueous medias such as water, buffer solutions with pH = 1.2, 4.5, and 6.8 in comparison to BER monohydrate. For instance, the solubilities of BER-ISN and BER monohydrate in water were 3.72 ± 0.22 and 1.42 ± 0.006 mg/mL, respectively, showing 2.62 times improvement. IDRs of BER-ISN and BER monohydrate were 29.90 ± 0.04 and 18.64 ± 0.27 mg/min/cm 2 , respectively, which was consistent with the solubility results. To explain the solubility behavior, phase solubility diagrams of BER monohydrate, ISN and BER-ISN in three pure organic solvents (ethanol, isopropanol and ethyl acetate) were performed according to the solubility product ( K sp ) and complexes formation ( K 11 ) theory. The predicted solubilities are consistent with experimental solubilities considering complexation effects. The Hildebrand solubility parameter (HSP) calculations support the results. Thus, BER-ISN cocrystal (1: 1) with improved solubility is a good candidate for further formulation development.
研究领域:
药学
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生物化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Pengfei Wang,Juntong Zhao,Yuman Zhang,Zhongjie Zhu,Liyuan Liu,Hongwei Zhao,Xianchao Yang,Xiaonan Yang,Xiaohong Sun,Mingxia He
Cocrystal is constructed to improve physicochemical properties of active pharmaceutical ingredient and prevent polymorphism via intermolecular interactions. However, recent examples on cocrystal polymorphs display significantly different properties. Even though some analytical techniques have been used to characterize the cocrystal polymorphic system, it remains unclear how intermolecular interactions drive and stabilize the structure. In this work, we study the cocrystal polymorphs of nifedipine (NFD) and isonicotinamide (INA) using terahertz (THz) spectroscopy. Form I and form II of NFD-INA cocrystals show spectral fingerprints in THz region. Temperature-dependent THz spectra display distinguished frequency shifts of each fingerprint. Combined with solid-state density functional theory (DFT) calculations, the experimental fingerprints and their distinct responses to temperature are elucidated by specific collective vibrational modes. The vibrations of hydrogen bonding between dihydropyridine ring of NFD and INA are generally distributed below 1.5 THz, which play important roles in stabilizing cocrystal and preventing the oxidation of NFD. The rotations of methyl group in NFD are widely distributed in the range of 1.5–4.0 THz, which helps the steric recognition. The results demonstrate that THz spectroscopy is a sensitive tool to discriminate cocrystal polymorphs. It has the potential to be used as a non-invasive technique for pharmaceutical screening.
研究领域:
药物化学
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物理化学
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高影响因子
RUSSIAN JOURNAL OF INORGANIC CHEMISTRY
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2026
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IF 1.5
Gao R.,Hong R. Y.,Hong H. L.,Liang C. Z.,Jiao Z. Z.,Jin S. W.,Li Z. Z.,Wang D. Q.
Three novel isonicotinamide(inic)-based Cu(II) complexes [Cu(inic) 2 (cbba) 2 ] (inic is isonicotinamide, cbba is 2-( p -chlorobenzoyl)benzoate) ( 1 ), [Cu(inic) 2 (mpa) 2 ] (mpa is 4-methoxyphenylacetate) ( 2 ), and [Cu(inic) 2 (tmca) 2 (H 2 O)] 2 ⋅CH 2 Cl 2 (tmca is 3,4,5-trimethoxycinnamate) ( 3 ) have been acquired by the injection of the carboxylates as the auxiliary ligands and characterized by using the X-ray crystallography, together with the elemental analysis, FT-IR, and thermogravimetric analysis techniques. In all the complexes, the Cu(II) ions are coordinated through two monodentate carboxylates to the two anions, forming approximately a plane. Each Cu(II) ion is then coordinated with the pyridine N atom of the inic molecules that behave as the monodentate ligands. The amide groups of the inic create the H-bonds with other amide and carboxylate residues, engendering a molecular crystal with the three-dimensional H-bond arrangement of the mononuclear units. The X-ray diffraction studies displayed that these complexes possessed mononuclear structures with the square planar/square-pyramidal coordination modes at the Cu(II) ions. The pair of the complementary N–H···O H-bonds between the amides of the inic molecules were set up in compounds 1 and 3 , making the dimer motif of inic, while there found the catemer motif of the inic molecules through using the intermolecular single N–H···O H-bond between the CONH 2 in 2 . The CH–O contacts derived from the py CH of the inic molecules were built in all the compounds. The intricate intra- and intermolecular classical H-bonds, O–C, O–O, Cl–Cl, CH 3 –CH/CH–CH, CH 3 –C, CH–O/CH 2 –O/CH 3 –O, CH–Cl/CH 3 –Cl, C–π, O–π, CH–π, and π–π associates are elucidated by using the X-ray crystallographic studies, driving the isolated complexes into the high-dimensional ordered supramolecular structures.
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高影响因子
CRYSTAL GROWTH & DESIGN
·
2025
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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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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
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2023
·Vol. 47
·期 28
·13279-13285
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IF 3.3
Junling Guo,Zhongyi Cheng,Lukasz Peplowski,Zhemin Zhou
Isonicotinamide has important roles and application prospects in pharmaceutical, medical, and materials sciences. The biosynthesis of isonicotinamide has great advantages over chemical methods, but the biosynthesis of isonicotinamide has been reported for three decades and has not been industrialized yet. In this study, a thermophilic NHase from Carbonactinospora thermoautotrophicus was selected and then its activity was substantially improved by a “toolbox” screening strategy. The specific activity of the βL48D mutant towards 4-cyanopyridine was 307.02 ± 3.50 U mg−1, which was 13.9 times higher than that of the WT C.t NHase (22.01 ± 1.30 U mg−1). The structural analysis demonstrated that introduction of Asp into the βLeu48 site resulted in a larger catalytic cavity and better substrate orientations. Finally, a recombinant strain E. coli BL21 of the βL48D mutant was cultured at high cell density in a 5 L fermenter for high-level isonicotinamide production, developing a powerful process for isonicotinamide bio-production. The yield of isonicotinamide reached 2.89 M (352 g L−1), the substrate (4-cyanopyridine) was exhausted and the conversion was 100%. These results prove that C.t NHase is a promising competitor for future industrial production of biosynthetic isonicotinamide.
研究领域:
生物化学
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工业微生物学
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药物化学
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高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2014
·Vol. 131
·期 17
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IF 1.64
Hongming Yuan,Zaochuan Ge,Shaojun Chen,Shiguo Chen,Haipeng Yang,Haitao Zhuo
This article demonstrates a comparative investigation about the effect of diisocyanate on pyridine containing shape memory polyurethanes (Py-SMPUs), which are synthesized with N , N -bis(2-hydroxylethyl)isonicotinamide (BINA) and four different diisocyanates: 1,6-hexanediisocyante (HDI), isophorone diisocyanate (IPDI), methylene diphenyl diisocyanate (MDI), and tolylene diisocyanate (TDI). Results show that all BINA–SMPU systems have amorphous reversible phase. Comparatively, the MDI–BINA and TDI–BINA systems show higher T g ; and the HDI–BINA and IPDI–BINA systems show better thermal stability. In addition, the HDI–BINA and the IPDI–BINA systems exhibit good thermal-induced shape memory effect and good moisture-sensitive shape memory effect due to their better moisture absorption properties. Particularly, the HDI–BINA system has better response speed and better shape recovery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40721.
研究领域:
材料科学
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高分子化学
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DOI
高影响因子
Inorganic and Nano-Metal Chemistry
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2021
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IF 1.716
Weiqiang Xu,KaiKai Hu,Shouwen Jin,Yuting Zhang,Daqi Wang
Transition metal carboxylates with O- and N-donor ligands are interesting for their structural features. Seven novel isonicotinamide(inic)-based metal complexes of [Cd(inic)2(L1)2(H2O)2] · 2H2O (1) (L1 = 2-chloronicotinate), [Cd(inic)2(L2)2(H2O)2] (2) (L2 = 2,4-dichlorobenzoate), [Cu(inic)2(L3)2] (3) (L3 = 4-chlorophenoxyacetate), [Cu3(inic)6(L4)2(HL4)2(H2O)2] · 2H2O (4) (L4 = azelate), [Zn(inic)2(L1)2(H2O)2] · (inic) · H2O (5), [Zn(inic)(L5)(H2O)4] (6) (L5 = 3-nitrophthalate) and [Zn2(inic)2(L6)2] · 5H2O (7) (L6 = 1,4-cyclohexanedicarboxylate) have been obtained by the introduction of the carboxylates by the common solution method and are structurally featured by different techniques of EA, IR spectra, TG and SCXRD analysis. The X-ray studies told that these complexes display mononuclear to trinuclear structures with octahedral/square-pyramidal geometry around the Zn2+, trigonal bipyramidal/octahedral at the Cu2+ and octahedral for the Cd2+. The inic in 1–7 are coordinated only in monodentate fashion with its ring N, while 5 has the lattice inic. The carboxylates coordinated to the metal in monodentate, chelating bidentate and bridging bidentate fashions. The pair of complementary N-H···O H-bonds from the CONH2 of the inic were found in all compounds except 7. Except 1 and 2, all other compounds bear the CH-O contacts from the pyridine CH of the inic. The intricate intra- and intermolecular classical H-bonds, CH-N, CH-O, CH-Cl, CH2-O, O-N, O-O, Cl-O, Cl-Cl, CH-π, CH2-π, C-π, N-π, Cl-π and π-π associations are elucidated by the X-ray crystallographic studies, which push the discrete complexes into high-dimensional ordered supramolecular structures.
研究领域:
化学
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材料科学
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晶体学
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DOI
高影响因子
Analytical Methods
·
2013
·Vol. 5
·期 20
·5615-5621
·
IF 1.855
Hongli Sun,Yiwei Wu
A new micellar electrokinetic capillary chromatography (MEKC) method combined with field-amplified sample injection (FASI) has been developed for the analysis of isonicotinamide and nicotinamide in whitening cosmetics and supplemented foodstuffs. Parameters affecting FASI preconcentration and MEKC separation were optimized systematically. Compared with direct MEKC, the sensitivity of FASI-MEKC was improved by 12.8- and 9.8-fold for isonicotinamide and nicotinamide, respectively. The detection limits (LODs) of isonicotinamide and nicotinamide were 0.051 μg mL−1 and 0.069 μg mL−1, respectively, with RSD (intraday) < 4.9% (n = 7, c = 0.5 μg mL−1) and RSD (interday) < 6.4% (n = 5, c = 0.5 μg mL−1). The proposed method was successfully applied in determination of isonicotinamide and nicotinamide in whitening cosmetics and supplemented foodstuffs with acceptable recoveries of 84.7–108.4%.
研究领域:
分析化学
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药物分析
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化妆品科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）