Curcumin (CUR) is a polyphenolic compound that exhibits potent anti-inflammatory activity. However, only a tiny amount of CUR is absorbed during oral administration, which is because CUR is difficult ...to dissolve in water. The aim of the research was to increase the solubility of CUR through the cocrystallization technique using isonicotinamide coformer (INIC) by solvent evaporation. Cocrystal characterization was carried out using a powder X-ray diffractometer (PXRD), a differential scanning calorimeter (DSC), a Fourier transform infrared spectrometer (FTIR), and a scanning electron microscope (SEM). Solubility was evaluated using the shaking method, while the anti-inflammatory activity test was carried out using the carrageenan induced mouse leg edema method. The resulting CUR-INIC (1:1) cocrystal has a diffractogram with new diffraction peaks of 2theta at 15.00, 16.22, and 22.89◦ compared to the individual diffractograms of CUR and INIC. In the cocrystal, CUR and INIC form intermolecular interactions of hydrogen bonds, resulting in a new solid phase with a melting point of 160.1◦C. The solubility of the CUR-INIC cocrystal in water was 73.1±0.23 ug/mL, which increased 14 times compared to the solubility of initial CUR, which was only 5.05±0.07 ug/mL. The CUR-INIC cocrystal showed a percentage of edema inhibition in mice (5 hours) 130% more potent than that of initial CUR. Therefore, CUR-INIC cocrystals can be used to improve CUR solubility to obtain more excellent anti-inflammatory effects.
In this study, five nicotinamide and isonicotinamide complexes were synthesized with X(CH2COOH)2 dicarboxylic acids (X: –NH–, –O–, –S–). They were structurally characterized by elemental analysis, IR ...spectroscopy and single crystal X-ray diffraction. Complex 1 is 1D polymer while the other complexes have mono-nuclear structures. In all complexes, three dimensional (3D) supramolecular network are generated through the O–H⋯O and N–H⋯O hydrogen bonds. The photoluminescence properties of complexes 3–5 were due to intra-ligand transitions. Moreover, the optical band gap calculated by the Kubelka–Munk function for complex 2 is 3.00eV which indicates the semi-conductive property.
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Five nicotinamide and isonicotinamide complexes with diverse dicarboxylic acids, {Cu(µ2-ida)(na)·H2O}n (1), Cu(oda)(H2O)2(ina) (2), Zn(oda)(H2O)2(na) (3), Zn(oda)(H2O)2(ina)·H2O (4) and Zn(tda)(H2O)2(ina)·2H2O (5), ida: 2,2′-iminodiacetate, NH(CH2COOH)2, oda: 2,2′-oxydiacetate, O(CH2COOH)2, tda: 2,2′-thiodiacetate, S(CH2COOH)2, na: nicotinamide and ina=isonicotinamide were synthesized and characterized by elemental analysis, IR spectroscopy and single crystal X-ray diffraction. In all complexes, ina and na ligands connected to metal centers from pyridyl nitrogen atom. In complex 1, ida ligand acts as a bridging ligand to form 1D chain while in the other complexes, oda and tda act as chelating ligands. In all complexes, three dimensional (3D) supramolecular networks are generated through the O–H⋯O and N–H⋯O hydrogen bonds. Moreover, thermal, photoluminescence and optical absorption properties were studied.
Three polymorphs (forms I, II and V) of isonicotinamide (INA) were mechanically flexible and exhibited one-dimensional (1D) plasticity. Anisotropic intermolecular interactions contribute to the ...plasticity of single crystals: weak dispersive interactions between slip planes such as 1D columns in forms I and II or 2D layers in form V were stabilized by strong hydrogen bonds, allowing the layer or column's surface to glide smoothly without hindrance. The disparity of intermolecular interactions on plastic properties of INA polymorphic crystals was confirmed by energy framework analysis, nanoindentation tests and micro-Raman spectroscopy. The crystal which exhibits plastic property provides a promising application in pharmaceuticals and material sciences.
Three polymorphs (form I, II and V) of isonicotinamide (INA) exhibited super flexibility with one-dimensional (1D) plasticity. The anisotropic intermolecular interactions with weak dispersive interactions between slip planes contribute to the bending performance of INA. Display omitted
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•We prepared ibuprofen-isonicotinamide co-crystal granules.•The granules were produced directly and continuously by a continuous-spray granulator.•The granulation conditions affected ...the particle size and the yield of the granules.•Compared to ibuprofen bulk, the granules improved the circularity and the flowability.•The co-crystallization did not change the solubility of ibuprofen.
The importance of granulation is paramount for tablet manufacturing, and is based on the fact that granulated powders are characterized by improved flowability, compressibility, segregation, and dust reduction. The aim of this study was to prepare and characterize continuous granules of high drug content by using a continuous-spray granulator (CTS-SGR). Ibuprofen (IBU), a drug of low-flowability, was selected as the model drug. As IBU has a low melting point and cannot easily granulate on its own, we employed isonicotinamide (INA) as a coformer that would allow us to prepare co-crystal granules containing 60 % IBU. The results of the undertaken differential scanning calorimetry and powder X-ray diffraction revealed that the IBU and the INA in the granules formed co-crystals. The granulation conditions affected the particle size and the yield of the granules; in fact, a low air supply temperature, a low atomizing air rate, and a high solution flow rate ensured a high granulation efficiency. Moreover, continuous granulation increased the yields of the formulations compared to those obtained through a short-run granulation, and high yields were obtained after applying a low atomizing air rate. The circularity of the granules exceeded 90 %, and their flowability improved when compared to that of the IBU bulk. The undertaking of dissolution studies revealed no change in the elution amount of IBU as a result of the co-crystallization. Our study shows that it is possible to produce high-content IBU granules in a direct and continuous manner through the co-crystallization of IBU and the use of a CTS-SGR.
Praseodymium (III) and dysprosium (III) isonicotinamide (INA) complexes grafted onto modified mesoporous MCM-41 with 3-chloropropyltriethoxysilane (CPTES)), as two novel catalysts, were synthesized. ...The catalysts were determined using SEM, Mapping, EDX, FT-IR, TGA, XRD, ICP, and BET analysis. The catalysts (MCM-41-INA-Pr and MCM-41-INA-Dy) were further studied for the oxidation reaction of sulfur-containing compounds. Catalytic results displayed that the MCM-41-INA-Pr and MCM-41-INA-Dy show high effectiveness for promoting the oxidation reaction of sulfur-containing compounds. The catalysts could be recycled for seven runs with negligible destruction of catalytic performance.
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•Two novel, and eco-friendly (MCM-41-INA-Pr and MCM-41-INA-Dy) catalysts were prepared and characterized.•These catalysts can be used for oxidation of sulfides and oxidative coupling of thiols.•The products were obtained in high to excellent yields in a short reaction time.•MCM-41-INA-Pr and MCM-41-INA-Dy catalysts could be reused several cycles without significant loss in activity.
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/cm2, 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 (Ksp) and complexes formation (K11) 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.
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The dehydration behavior of pharmaceutical hydrates has a great influence on its physiochemical properties such as stability, dissolution rate and bioavailability. However, how the ...intermolecular interactions vary during dehydration process remains elusive. In this work, we employed terahertz time-domain spectroscopy (THz-TDS) to probe the low-frequency vibrations and the dehydration process of isonicotinamide hydrate I (INA-H I). Theoretical solid-state DFT calculation was conducted to reveal its mechanism. Vibrational modes which are responsible for the THz absorption peaks were decomposed for better understanding the characters of these low-frequency modes. The result suggests translational motion is the dominant component for water molecules in THz region. Evolution of the THz spectrum of INA-H I during dehydration provides direct evidence of the variations of crystal structure. Based on the THz measurements, a two-step kinetics mode including first-rate reaction and three-dimensional nuclei growth is proposed. And we figure that the low-frequency vibrations of water molecules are the origin of dehydration process of hydrate.
•Five solid forms have been prepared and characterized.•The interactions were investigated by SCXRD.•The synthons have been analyzed.
Cocrystallization of the commonly available isonicotinamide, with ...a series of carboxylic acids gave a total of five new anhydrous and hydrous multicomponent solid forms: (isonicotinamide)2: (suberic acid) (L)2 · (H2sub), H2sub = suberic acid (1), (isonicotinamide)2: (α-ketoglutaric acid): H2O (HL+)2 · (kga2−) · H2O, kga2− = α-ketoglutarate (2), (isonicotinamide): (1,2-phenylenediacetic acid) (L) · (H2pda), H2pda = 1,2-phenylenediacetic acid (3), (isonicotinamide): (4-nitrophthalic acid) (HL+) · (Hnpta−), Hnpta− = 4-nitrohydrogenphthalate (4) and (isonicotinamide)4: (butane-1,2,3,4-tetracarboxylic acid) (L)4 · (H4bta), H4bta = butane-1,2,3,4-tetracarboxylic acid (5). The five solid forms have been characterised by XRD, IR and EA and their melting points were also reported. Their structural and supramolecular aspects are fully analyzed.
The result shows that 2 and 4 are organic salts with only the aryl N in L protonated, 1, 3 and 5 are co-crystals. The crystal packing is interpreted by the strong N-H···O, O-H···N and O-H···O hydrogen bonds. The carboxamide dimers were existed in all solid forms by a pair of N-H···O hydrogen bonds. Further inspection of the crystal packing told that a different set of additional CH-O/CH2-O, CH-N, O-C, O-O, O-N, O-π and π-π associations contribute to the stabilization and expansion of the total high-dimensional (2D-3D) structures. For the delicate balance of the various weak nonbonding interactions these structures adopted homo/hetero supramolecular synthons or both and the common R21(7) and R22(8) graph sets have been observed in all solid forms due to the interplay of hydrogen bonds and non-covalent associations.
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Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new ...challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal T m, low melt viscosity, and rapid solidification upon cooling.
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