Solid state of a new flavonoid derivative DA-6034

DA-6034 is a new synthetic flavonoid known to possess anti-inflammatory activity. The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of DA-6034. Six crystal forms, one hydrate form and five solvates, of DA-6034 have been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and powder X-ray diffractometry (PXRD). From the DSC and TG data it was confirmed that Form 1 is monohydrate; Form 2 is DMSO solvate; Form 3 is 1/2 DMSO solvate; Form 4 is 1/2 methyl ethyl ketone solvate; Form 5 is 1.5 H₂O, 1/2 acetic acid solvate; Form 6 is 1/2 H₂O, 1/4 butanol solvate. The PXRD patterns of the six crystal forms were different respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer at 37 ± 0.5 °C, the solubility of solvates was higher than that of Form 1.     

Polymorphic and Thermodynamic Study of Indomethacin

Indomethacin is known to exhibit polymorphism. As a consequence the various forms have different solubilities and may have different bioavailabilities. This study has been carried out with the following techniques: calorimetry, differential scanning calorimetry (DSC), thermogravimetric analysis (TG), X-ray diffraction and thermomicroscopy. Two solid forms have been prepared and studied: their melting temperature and their enthalpy of fusion are determined. The heat capacity and heat content were measured vs. the temperature for these two solid forms and for the liquid phase. This is fundamental for the determination of the stable form. More of this, with a view to study phase diagrams of indomethacin with another compound (solvent or not), the knowledge of the C _p of the various forms is necessary for calculation of the liquidus curve, this allows to minimize the number of experiments. This revised version was published online in August 2006 with corrections to the Cover Date.     

Thermal analyses (TGA and DSC) of some spironolactone solvates

Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies have been performed on a commercial preparation of spironolactone and on five solvates (acetonitrile, ethyl acetate, ethanol, methanol, and benzene) prepared from it by recrystallization at room temperature. The results of these studies are discussed and compared with those recently reported in the literature for similar preparations. The variable behaviour of these solvates in their release (and partial retention) of solvent before the onset of melting, meant that their stoichiometry had to be measured by elemental microanalyses. Solvent loss from solvate decomposition was followed by thermogravimetric analysis (TGA). Solvate decomposition and spironolactone melting temperatures and enthalpies were determined by differential scanning calorimetry (DSC). The parent substance and two of the solvates (methanol and ethanol) exhibited small exotherms in addition to the expected endotherms.     

Thermoanalytical and spectroscopic studies on different crystal forms of nevirapine

This study is aimed at exploring the utility of thermoanalytical methods in the characterization of various polymorphs and solvates of nevirapine. The different forms obtained by recrystallization of nevirapine from various solvents showed morphological differences in SEM. The presence of polymorphic forms is suggested by single sharp melting endotherm different from original sample in DSC and no mass loss in TG, while appearance of desolvation peak in TG indicated the formation of solvates. The higher desolvation temperatures of all the solvates than their respective boiling point indicate tighter binding of solvent. The changes in the crystal lattice were demonstrated by X-ray powder diffraction studies. The enthalpy of fusion rule indicated the existence of monotropy in polymorphic pairs I/O and II/O, while I/II is enantiotropically related. The enthalpy of solution, an indirect measure of the lattice energy of a solid, was well correlated with the crystallinity of all the solid forms obtained. The magnitude of ΔH _sol was found to be ?14.26  kJ mol^?1 for Form V and ?8.29  kJ mol^?1 for Form O, exhibiting maximum ease of molecular release from the lattice in Form V. The transition temperature was found to be higher than the melting of both the forms except for polymorphic pair I/II providing complementary evidence for the existence of monotropy as well as enantiotropy in these polymorphic pairs.     

Thermodynamic properties of polymorphic forms of theophylline. Part I: DSC,TG, X-ray study

The physicochemical properties of theophylline hydrate and anhydrous polymorphic forms I and II were evaluated using crystallographic and calorimetric method. This study has been carried out with the following techniques: differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and X-ray diffractometry. The X-ray patterns on powder for investigated compounds are presented.     

Physicochemical characterization of tamoxifen citrate pseudopolymorphs, methanolate and ethanolate

Two novel pseudopolymorphs, methanolate and ethanolate of tamoxifen [(Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine]citrate, were prepared in addition to forms A and B reported previously. Their crystalline forms were identified and characterized by powder and single crystal X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, scanning electron microscopy and diffuse reflectance infrared Fourier-transform spectroscopy, and their physicochemical stability was also evaluated. The results of single crystal X-ray analysis and thermogravimetric analysis of methanolate and ethanolate suggested that the stoichiometry of tamoxifen citrate : methanol and tamoxifen citrate : ethanol could be composed of a 1 : 1 molecular ratio for both solvates. The results of physicochemical stability evaluations at 75 and 97% RH at 40 and 60 degrees C indicated that the metastable form A was quite stable for at least 2 months even under severe storage conditions, whereas methanolate immediately transformed to a crystalline mixture of forms A and B, and subsequently changed to the stable form B.     

Preparation and Solid-State Characterization of Eltrombopag Crystal Phases

Eltrombopag, of C₂₅H₂₂N₄O₄ chemical formula, is a drug used against thrombocytopenia, marketed worldwide under different tradenames in the form of its bis-olamine salt. The free acid (CAS no. 496775-61-2) is an intermediate species used for the final drug isolation and is reported to crystallize in more than 20 distinct crystal forms, including a large number of hydrates and solvates. Their identification, and, ultimately, their quantification in industrial lots require the usage of accurately measured X-ray powder diffraction pattern, as well as the assessment of the metrical features (crystal symmetry and lattice parameters), nowadays accessible by powerful crystallographic software. Here, the complete indexing of 13 monophasic samples, prepared using literature or newly tailored crystallization methods, jointly to simultaneous thermogravimetric and calorimetric analyses and to variable temperature X-ray diffraction studies, provide a clear picture of the stability fields of the different crystal phases and their mutual interconversion processes, leading, in a few cases, to new and unexpected crystalline polymorphs or solvates of the pristine unsolvated Form I.     

Thermochemical Investigation of Some Selected Solvates of Calix[4]resorcinarene

Lipophilic calix[4]resorcinarene derived from lauryl aldehyde forms stable crystalline solvates with a range of organic solvents: acetone, 1,4-dioxane, methylethylvketone, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, butyronitrile, methanol, 1,2-dimethoxybenzene and acetonitrile. The composition and thermal stability of these solvates was followed by thermogravimetric method, indicating a stoichiometry ranging from 1 to 3 (calixresorcinarene/solvent). The activation energy was evaluated for the selected solvates. Molecular modelling, using Hyperchem 5.0 software, was applied to the selected solvates. This revised version was published online in August 2006 with corrections to the Cover Date.     

Crystal solvates of porphyrins and metalloporphyrins

The published data on the crystal solvates with nonpolar aromatic and electron-donor compounds obtained using different research methods as well as our own experimental results obtained by thermogravimetric analysis of the porphyrins and metalloporphyrins of natural and synthetic origin are generalized. The influence of the molecular structure of the porphyrins and metalloporphyrins on the composition, structural parameters, thermal and energy stability of crystal solvates formed through specific ??-and ??-complexes with molecular ligands are considered.     

Crystal forms of a capsaicin derivative analgesic DA-5018

DA-5018 is a new capsaicin derivative and has analgesic effect. The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of DA-5018 and the transformation of crystal forms. Eight crystal forms of DA-5018 have been isolated by recrystallization and characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). The PXRD and DSC patterns of the eight crystal forms were different respectively. In the dissolution studies in simulated intestinal fluid at 37±0.5°C, the solubility of Form 2 was the highest. And the solubility in water decreased in rank order: Form 2>Form 3>Form 1>Form 5>Form 7>Form 4>Form 6>Form 8. Eight crystal forms were shown to have a good physical stability at room temperature for 60 days.     

Study of the polymorphic behaviour of some local anesthetic drugs

The local anesthetic drug tetracaine hydrochloride is described in the Europ. Pharmacopea with a melting point of 148°C or with a range of 134 to 147°C due to the melting points of two other forms. The polymorphic behaviour of tetracaine hydrochloride has been studied by using thermal treatments, storage at 92% r.h., crystallizations and equilibrations with saturated solutions. Samples were characterized by X-ray diffraction, IR, thermal analysis and elemental analysis. Since some findings were difficult to interpret, temperature resolved X-ray diffraction was used additionally for the understanding of the thermal behaviour of tetracaine hydrochloride. In this study the polymorphic behaviour of some other local anesthetic drugs is compared. Ten different forms of tetracaine hydrochloride: six anhydrous crystalline forms, an amorphous form, a hemihydrate, a monohydrate and a tetrahydrate were identified. The relationships between all forms are given. The heating curve of the commercial form 1 is very dependent on the heating rate. This anhydrous form 1 is the thermodynamic stable modification at ambient temperature. The form 2 is reversibly enantiotrope to form 1. The four other modifications called 3, 4, 5 and 6 are monotropes of form 1. Only forms 1 and 5 are stable at ambient temperature. Form 1 is hygroscopic only at high humidity level of 92% r.h., form 5 is hygroscopic at 61% r.h. Both transform into the monohy-drate. No polymorphic forms of tetracaine base, dibucaine hydrochloride, procaine hydrochloride or prilocaine hydrochloride were found. The commercial form of bupivacaine hydrochloride is a monohydrate. Thermal treatment at 200°C gives one anhydrous form. As demonstrated by temperature resolved X-ray diffraction two other forms are detected by heating and cooling processes between 100 and 170°C. Equilibrations and crystallization experiments show that solvates are easily obtained in different solvents. Temperature resolved X-ray diffraction is a very efficient tool as a support to DSC for the identification of the transition processes and interpretation of thermal events and thermodynamic relationships. Equilibration experiments are very adequate to find out the thermodynamically stable form at ambient temperature (solvent mediated transitions).     

Polymorphic Characterization,Pharmacokinetics, and Anti-Inflammatory Activity of Ginsenoside Compound K Polymorphs

Polymorphism exhibits different physicochemical properties, which can impact the bioavailability and bioactivity of solid drugs. This study focused on identifying the polymorphs of ginsenoside compound K (CK) and studying their different behaviors in pharmacokinetics (PK) and pharmacodynamics (PD). Four CK polymorphs (form I, II, III, and IV) from organic solvents were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD). A feasible LC-MS/MS method was exploited to determine the PK parameters. Form II displayed the most exposure, followed by form I, III, and IV. Notably, all forms showed sex dimorphism, and the bioavailability in the female group was about two-fold higher than in the male group. The PD properties were investigated in carrageenan-induced acute paw inflammation, and form II at 20 mg/kg showed significant inhibition of edema by 42.7%. This study clarified the polymorphic, PK, and PD characters of four crystal forms of CK, and the data suggested that form II had the best efficacy for drug development.     

Preparation and properties of calcium silicate hydrate-poly(vinyl alcohol) nanocomposite materials

Summary A series of calcium silicate hydrate (C-S-H)-polymer nanocomposite (C-S-HPN) materials were prepared by incorporating poly(vinyl alcohol) (PVA) into the inorganic layers of C-S-H during precipitation of quasicrystalline C-S-H from aqueous solution. The as synthesized C-S-HPN materials were characterized by Fourier-transform infrared photoacoustic (FTIRPAS) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy/energy dispersed spectroscopy (SEM/EDS), thermogravimetric analysis (TG), differential thermogravimetry (DTG) and differential scanning calorimetry (DSC). The XRD peaks of C-S-HPN materials suggest the intermediate organizations presenting both intercalation of PVA and exfoliation of C-S-H. The SEM micrographs of C-S-H, PVA and C-S-HPN materials with different PVA contents exhibit the significant differences in their morphologies. Effects of the material compositions on the thermal stability of a series of C-S-HPN materials along with PVA and C-S-H were studied by TG, DTG and DSC. Three significant decomposition temperature ranges were observed in the TG curves of all C-S-HPN materials.     

Physicochemical characterization of nicergoline and cabergoline in its amorphous state

Formulation of poorly water-soluble crystalline drugs into their more soluble amorphous form is a common approach for improving their bioavailability. In this study, the amorphous forms of nicergoline (NIC) and cabergoline (CAB) were obtained by different methods (melting and precipitation under solvent evaporation). The physicochemical characteristics of the samples were determined by HPLC, differential scanning calorimetry (DSC), thermogravimetry, and X-ray powder diffractometry. The physical stability of the amorphous forms was investigated by DSC by considering how the onset temperature and the enthalpy content at the glass transition vary with aging time and temperature. Using the Kohlrausch–Williams–Watts equation on the data obtained from the experiments, the “mean molecular relaxation time constant” (τ) was estimated. This parameter was used to understand the stability of NIC and CAB in their glassy state at different temperatures, and results showed that their stability is adequate to enable the formulation of these drugs into solid dosage forms.     

Study of thermal decomposition of silver acetate

Thermal decomposition of silver acetate was studied (TG, DSC, mass-spectrometry, X-ray analysis, electron microscopy). Non-isothermal thermogravimetric data (obtained at two different rates of linear heating) were used for kinetic studies. Kinetic parameters were calculated only for the chosen decomposition step.     

Cryomodification of drugs: Micronization and crystalline structures of 1-(aminomethyl)-cyclohexaneacetic acid

Cryochemical modification is a method of micronization and changing of the crystalline structure of organic substances that in application with drug substances may lead to the improvement of their biopharmacological properties. This method was successfully developed for a chemically labile compound named gabapentin [1-(aminomethyl)-cyclohexaneacetic acid]. According to the data obtained by X-ray diffraction, FTIR spectroscopy, and differential scanning calorimetry (DSC), the formation of two kinetically stable polymorphic modifications of gabapentin (forms with melting points of 157°C and 163°C), which are different from the initial commercial one (with a melting point of 153°C) was observed. These two forms are well known, but the advantage of this work is in developing a new method of their production that excludes the use of any solvents, which is very important for environmental safety.     

环丙沙星水合物与无水合物晶型的相互转变(英文)

化合物的水合状态有赖于结晶溶媒中水的活度(aH2O).通过制备不同体积比水-有机溶媒的潜溶剂来控制aH2O,用粉末X射线衍射(PXRD)、热重分析(TGA)和差示扫描热量(DSC)等方法表征在具有不同aH2O的水-甲醇中平衡一段时间后的过剩环丙沙星固体的结晶状态.同时采用高效液相色谱测定环丙沙星水合物、无水合物以及它们的混合物在具有不同aH2O的水-甲醇混合溶液中的溶解度.结果表明溶解度变化规律与在相应aH2O的水-甲醇中多余固体的晶型变化规律基本一致.利用实验所得数据构建了环丙沙星无水合物/水合物相稳定性与aH2O的关系图.将该图像与放置于室温以及一定相对湿度条件下时间长达十二周的样品的PXRD数据对比,表明本实验所用的研究方法能够快速、精确地预测无水合物与水合物之间的相互转变过程以及水-有机溶媒的aH2O对它们的相对稳定性的影响.     

Synthesis, spectroscopic characterization and X-ray structure of [1,2a]benzimidazol-2-yl amidine

[1,2a]Benzimidazol-2-yl amidine was synthesized by adding cyclopentanamine to iminoester in ethanol. The structure of amidine 1 was characterized by IR, 1H NMR, 1H-1H NOESY, 13C NMR, DEPT, XHCOR spectra, thermogravimetric analysis (TGA), differential thermal analysis (DTA), differential scanning calorimetry thermograms (DSC), elementary analysis as well as by X-ray diffraction. The single crystals suitable for X-ray measurement were obtained by recrystallization at room temperature. The amidine group of a model was found to have Z configuration in the crystal. This compound crystallizes in a P2(1)/n monoclinic unit cell with parameters a=12.679(2) ?, b=8.468(3) ?, c=13.108(2) ?, β=96.538(2)°, V=1398.2 ?3 and Z=4.     

Rapid synthesis of tin (IV) oxide nanoparticles by microwave induced thermohydrolysis

Tin oxide nanopowders, with an average size of 5 nm, were prepared by microwave flash synthesis. Flash synthesis was performed in aqueous solutions of tin tetrachloride and hydrochloric acid using a microwave autoclave (RAMO system) specially designed by the authors. Energy dispersive X-ray analysis (EDX), X-ray powder diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area analysis, nitrogen adsorption isotherm analysis, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM), were used to characterize these nanoparticles. Compared with conventional synthesis, nanopowders can be produced in a short period (e.g. 60 s). In addition, high purity and high specific surface area are obtained. These characteristics are fundamental for gas sensing applications.     

Influence of solid corrodents on high-temperature oxidation of cobalt powder

Complexes between members of a homologous series of alkylparabens and b-cyclodextrin (b-CD) have been prepared by both kneading and co-precipitation methods and their behaviour studied by differential scanning calorimetry (DSC), thermogravimetric (TG), infrared (IR) and powder X-ray diffraction (PXRD) techniques. PXRD revealed that complexation did occur by both the kneading and co-precipitation methods. DSC and IR techniques confirmed these results and TG indicated the presence and number of water molecules in each complex. This revised version was published online in July 2006 with corrections to the Cover Date.