High Impurity Levels Research Articles

Screening methods for impurities in multi-sourced fluoxetine hydrochloride drug substances and formulations

Gradient high-performance liquid chromatography (HPLC) and gas chromatography were applied as screening methods for determination of impurities in fluoxetine hydrochloride drug substances and formulated products from multiple sources. Nuclear magnetic resonance spectroscopy was also used for identification of excipients and some residual solvents. Thirty potential impurities and excipients were investigated. Several impurities were observed in generic products using gradient HPLC that were not detected with isocratic pharmacopeial methods for fluoxetine hydrochloride. Analysis of drug substance samples and capsule formulations from many different suppliers showed a wide variation in quality which, in many cases, would go undetected using isocratic methods. The quality of the innovator's product and some generic samples was high, but many generic samples contained high levels of impurities. A new impurity, N-benzyl fluoxetine, was observed in some generic samples at levels as high as 0.9%. The gradient HPLC method was also used for stability studies and established that generic capsules formulated with lactose were less stable under accelerated conditions than those formulated without lactose.

Analysis of impurities of isopropyl myristate by gas-liquid chromatography

Isopropyl myristate (tetradecanoic acid isopropyl ester) is commercially available in different qualities with specifications for content as low as 90%. Analysis by gas-liquid chromatography with flame ionization detection revealed up to four impurities exceeding the 0.1% level. Impurities identified by gas chromatography-mass spectrometry were the isopropyl esters of C 12 and C 16 fatty acids (dodecanoic acid and hexadecanoic acid, respectively) and the respective ethyl and methyl ester of C 14 fatty acid (tetradecanoic acid). A relatively high level of impurities was also found in the standard material specified by German pharmacopoeia DAB 10 for calibration of response factors for internal standard quantitation. Therefore, results of quantitative analysis were found to be significantly different depending on the method used for quantitation.

Preparation and Properties of High-Purity β-FeSi2 Single Crystals

High-purity single crystals are necessary to investigate the intrinsic properties of undoped β-FeSi2 in dependence on the deviation from the stoichiometric composition. Therefore, iron was prepared with high purity with respect to metallic as well as non-metallic impurities and used as initial material for growing β-FeSi2 single crystals by chemical vapour transport in a closed system. By the optimization of the whole preparation process a single crystal purity of about 99.996% by weight could be achieved. The content of the main electrically active elements was lowered to about 20 wt ppm. Starting from a certain purity only n-type single crystals were obtained in equilibrium with FeSi as well as with Si. It is concluded that the p-type conductivity of undoped single crystals reported in literature results from non-intentional doping by the high impurity level of the source material used. Differences were found in the physical properties between crystals prepared at the upper and the lower phase boundaries of β-FeSi2, indicating that the single crystal properties were significantly influenced by intrinsic defects caused by deviations from the strictly stoichiometric composition and not by extrinsic factors. In contrast to the crystals grown from FeSi/FeSi2 and FeSi2, a new shallow donor state with an activation energy of 23 meV was found in the crystals grown from the FeSi2/Si source.

Boundary sliding behaviour in high-purity Pb-62 % Sn

Abstract Boundary sliding behaviour in high-purity Pb-62% Sn containing 5 ppm of impurities has been investigated in tension at T = 422 K by measuring the individual offsets across boundaries. In the investigation, the alloy was tested at various initial strain rates, in the range of 5·33 × 10−7 to 1·33 × 10−1 s−1. The experimental results show that the contribution of boundary sliding to total strain at low strain rates is significant (about 60%) and comparable to that at intermediate strain rates (the superplastic region in alloys of high impurity levels). Also, the results reveal that, in general, there is no considerable difference in the average value of sliding offsets at the three types of boundary: Pb-Pb, Sn-Sn and Pb-Sn. However, contribution of sliding at interphase boundaries, Pb-Sn, appears to be more significant than that at intercrystalline boundaries, Pb-Pb and Sn-Sn. The above results are discussed in the light of recent data regarding the effect of impurities on superplastic flow.

Infrared to green up conversion in Er 3+:CaF 2 layers grown by molecular beam epitaxy

Up conversion emission of Er 3+ ions is reported for the first time for the case of molecular beam homoepitaxial CaF 2:Er 3+ thin layers. In contrast with the case of the corresponding bulk material the layers have been doped up to a high level of active impurity without any degradation of the crystal quality. The up converted green emission has been studied under excitation in the region of diode laser emission, at around 800 nm. The green emission intensity has been investigated as a function of the excitation power as well as the Er concentration. In the latter case, a quadratic dependence is obtained revealing the participation of Er 3+ pairs in the up conversion process. The mechanism and the centers responsible for this up conversion phenomenon are discussed and the results are compared with those relative to the corresponding bulk crystals.

Kinetics of polycyclotrimerization of 4,4′-thiodiphenylcyanate

Polycyclotrimerization of 4,4′-thiodiphenylcyanate was studied by means of differential scanning calorimetry. Samples of different impurity levels or different catalyst loadings ( n-nonylphenol (NP), 1 to 10 phr) were studied. In the absence of added catalyst, the sample with higher impurity level (most likely residual water) underwent polycyclotrimerization at a lower temperature range than the sample of comparatively higher purity, although both samples shared the same apparent activation energy ( E a = 93 kJ mol −1) and exhibited similar autocatalysed first-order characteristics. The lowering of the reaction temperature range was more significant in the presence of NP. Interestingly, kinetic features in this case were quite different from the uncatalysed counterpart: in addition to the expected decrease in the apparent activation energy ( E a = 75 kJ mol −1, independent of the catalyst concentration), the cure reaction followed an autocatalysed second-order kinetics. These observations are explained in terms of a mechanistic scheme in which the competition between hydroxyl-catalysed and autocatalytic paths is considered. In particular, formation of NP aggregates ((NP) m , where m ≈ 7) is proposed to account for the less-than-additive catalytic capacity with increasing NP level.

Synthesis and structural characterisation of YBCO related phases containing cobalt

The synthesis of (Nd 1.5Ce 0.5)Sr 2CoCu 2O 91 a fluorite-type block material containing Co 3+, was recently reported in an impure form with its structure related to YBCO with Y 3+ replaced by a fluorite-type block of composition (Nd,Ce) 2O 2, Ba 2+ by Sr 2+ and the copper on the Cu1 sites wholly by Co 3+. This material was reported to be tetragonal, in contrast to its non fluorite block analogue YSr 2CoCu 2O 7, which exhibits long range directional ordering of chains of corner linked CoO 4 tetrahedral, producing orthorhombic symmetry. In this study the presence of a high level of impurities was confirmed and attributed to the formation of the perovskite impurity NdCoO 3 and subsequently a single phase product was synthesised when neodymium was replaced by yttrium, forming (Y 1.5Ce 0.5)Sr 2CoCu 2O 9. Neutron diffraction indicates the presence of long range directional order of CoO 4 tetrahedra chains. No superconductivity was observed.

NMR Spin Lattice Relaxation in NITROGEN-Doped 6H Silicon Carbide

ABSTRACTNuclear magnetic resonance (NMR) spin lattice relaxation is highly sensitive to the nature, amount, and homogeneity of unpaired-electron-containing impurities in silicon carbide and similar solids, and is a promising tool for the study of dopants and impurities. In nitrogen-doped 6H silicon carbide, 13C and 29Si NMR spin lattice relaxation is highly site-dependent. Not only do carbon sites relax much more rapidly than the corresponding silicon sites, but also there are unprecedented differences in relaxation efficiency among the different carbon (and silicon) sites, consistent with much higher unpaired electron density at the higher-symmetry (Types A and B) sites than at the lowest-symmetry (Type C) site. In contrast, all sites relax at equivalent rates in undoped samples and in commercial abrasive grade material with high levels of impurities, although there are large differences in relaxation efficiency among samples. The change in the nature of the relaxation process, from exponential in high-purity to stretched exponential in lower-purity samples, is apparently related to changes in unpaired-electron mobility.

Some aspects of diffusion in ceramics

Experiments of diffusion are more difficult in ceramics than in metals, because of specific physical, chemical and mechanical properties of ceramic materials. Due to their high melting point, the amount of point defects is generally much less than in metals at the same temperature. That implies very low diffusion coefficients, comparatively to diffusion coefficients measured in metals. The nature of the chemical bond of ceramics gives rise to stronger bonding than in metals and less ability to solve impurities. In these conditions, more segregation and precipitation effects are to be expected in ceramics and these effects may have an influence on the values of the diffusion coefficients. The interpretation of diffusion coefficient values needs a good knowledge of the nature and amount of defects, which are not so easy to control and which depend on the way used to prepare the samples destined to diffusion tests. The aim of this paper is not to give a review of all the values of diffusion coefficients obtained in all ceramics, but to point out some difficulties encountered in determination of diffusion coefficients : penetration depths, comparatively high level of impurity or dopant content in regard with the low amount of intrinsic defects and segregation of impurities to the grain boundaries and to the surface. Examples are given for alpha alumina and chromia.

直島製錬所の鉛製錬（三菱マテリアル（株））

Lead smelter at Naoshima was previously by conducted by Mitsubishi Cominco Smelting Co., Ltd., a joint venture company between Mitsubishi Materials Corp. and Cominco Canada Ltd. At that time, the extremely clean lead concentrate from Cominco's Pine Point Mine was solely treated. Therefore pyrorefined lead with four nine grade was produced without any further processing like the electrolytic refining. However, due to depletion of the mine, Cominco withdrew from the joint venture in September 1991. The lead smelter was taken over by Mitsubishi and it started as a custom smelter to treat several foreign lead concentrates, some of them contain high levels of impurities. As the produced crude lead was required to be electrolytically refined to meet with the stringent quality demand, a lead refinery with a capacity of 40, 000 mtpy was newly constructed, and started its operation in March 1992. It was designed to be highly mechanized and has been equipped with large electrolytic cells.

Selective zinc extraction from complex copper/zinc sulphide concentrates by pressure oxidation

Currently the world demand for non-ferrous metals can still be met by simple ores treated in a conventional manner. However, mineral resources are finite and as these reserves become depleted, attention must be focused on utilizing the more complex sulphide deposits. Frequently complex sulphide ores exhibit poor metallurgical response to conventional froth flotation. Since hydrometallurgical processes can tolerate lower metal grades and higher impurity levels than can conventional pyrometallurgical processes, treatment of bulk flotation concentrates is conducive to hydrometallurgical methods. The application of bulk flotation results in a simplified milling flowsheet and is capable of producing higher metal recoveries and revenues with respect to conventional smelter contracts. The primary objective was to develop hydrometallurgical process conditions which would enable selective pressure leaching of copper/zinc bulk flotation concentrates to extract zinc producing a zinc electrolytic solution. The upgraded leach residue containing the unreacted copper sulphide and precious metals would be treatable by conventional copper smelting. Zinc was selectively extracted from several complex Cu/Zn concentrates by utilizing various combinations of temperature and oxygen concentration in the pressure leaching process. A bulk concentrate grading 12.2% Cu, 3.8% Pb, 22.2% Zn, 1.4 g/t Au and 184 g/t Ag was pressure leached at 210°C with a 50% oxygen concentration at an over-pressure of 689 KPa with a retention time of 180 minutes. Extractions of zinc, and copper from the concentrate were 99%, and 0.32% respectively. The grade of the residue produced was approximately: 26% copper, 8.8% lead, 0.5% zinc, 435 g/t silver, 3.5 g/t gold and 42% iron. Similar results were also obtained from two bulk concentrates of different ore deposits.

Low pressure and low temperature gallium arsenide homoepitaxy employing in-situ generated arsine

Removed from the deposition region, an upstream hydrogen microwave plasma etches a surface of solid arsenic located downstream to generate arsenic hydrides. The latter are used with trimethylgallium (TMGa) to achieve low temperature (400–490° C) and low pressure (750 mTorr) homoepitaxial GaAs films. No active or afterglow plasma exists in the growth region. The homoepitaxial growth activation energy of 62 kcal/mole is consistent with the heterogeneous decomposition of TMGa in the absence of arsine. Precursor V-III ratios as low as 0.25 are used to achieve homoepitaxial films, but with high levels of carbon impurities (1019 to mid 1020 cm−3). Carbon incorporation increases at low V-III ratios (0.25 to 0.5) for increasing temperatures with an activation energy of 23 kcal/mole. As the V-III ratios are increased above 1.0, the carbon incorporation activation energy decreases slightly to 15 kcal/mole.

Vapor HF Etching for Low Temperature Silicon Epitaxy

ABSTRACTWe have evaluated the use of HIF vapor cleaning using an Advantage Edge 2000 commercial etcher as a preclean for low temperature UHV/CVD silicon epitaxy (LTE). Surface analysis by contact angle, XPS and Optically Stimulated Electron Emission (OSEE) measurements indicate that vapor HF treated surfaces have higher levels of impurities and are less stable than surfaces dipped in 10:1 diluted HF. Interfacial SIMS measurements and defect analysis using plan-view TEM after epitaxial growth indicate that the vapor treated samples also had higher levels of interfacial oxygen and surface defects. The results indicate that vapor HF precleaning is less effective for LTE than an aqueous HF dip since it provides poorer quality hydrogen passivation of the silicon surface.

The Influence of Impurities on Cobalt Silicide Formation

Cobalt silicide formation has been studied using thin films of Co on Si wafers with different impurity contents in the metal and with thin or thick native oxide at the Co/Si interface. The incorporation of impurities into the film was controlled by changes of the pressure during Co deposition. Two RTP systems with two different annealing ambients and heat sources were used for silicidation. For Co films with low contaminant level, thin or thick native oxide can be dissolved and good quality is formed. For Co films with high impurity level in the presence of thick native oxide, the silicidation can be performed, delayed, or even inhibited, depending on film thickness and annealing conditions.

The effects of impurities on the light-induced degradation of hydrogenated amorphous silicon

Amorphous silicon samples with an intentionally modulated impurity content at concentrations below 1 at.% were grown by the glow discharge deposition technique. The impurity profiles were determined by secondary-ion mass spectroscopy (SIMS) measurements and the spatial distributions of deep defects were determined by junction capacitance profiling measurements before and after light-induced degradation. For the case of intentionally added carbon, we found a significant enhancement in the concentration of light induced defects in regions with higher impurity levels such that a carbon level of 0.5 at.% leads to an additional (1–2) × 10 16 cm −3 increase in defects after light soaking.

Determination of the deuterium temperature profile in magnetic fusion plasmas

A new experimental method for determining the radial deuterium temperature profileTD(R) in axisymmetrical toroidal fusion plasmas is presented. The method is based on a generalized Abel inversion of neutron brightness data providing the radial neutron emissivity profile of the plasma. This profile, combined with information on the deuterium density profile, is used to determineTD(R) under the assumption that the ion velocity distribution is Maxwellian. Results are presented here from the analysis of JET data. It is found that, for typical JET plasma conditions, the dominant source of uncertainty arises from the high plasma impurity level and the fact that it is poorly known; these problems can be expected to be remedied and neutron brightness measurements would be expected to be very effective (especially in high-density plasmas) as aTD(R) diagnostics.

Electrochemical characteristics of silver treated cadmium selenide single crystal electrodes

CdSe electrodes dip-treated in 10 mM AgNO 3 solution behave almost as a silver electrode because the CdSe/Ag interface has ohmic characteristics. On the other hand, CdSe electrodes modified by vacuum evaporation of silver and then heat-treated in a He atmosphere showed negligible dark currents in the anodic potential region. Cathodic as well as anodic photocurrents were observed at this electrode. The electrode was relatively stable and although the anodic photocurrent at this electrode was initially much smaller than the anodic photocurrent at the unmodified CdSe electrodes, it became larger than the anodic photocurrent observed at the unmodified electrode after illumination for 1000 s. A quite unusual quantum efficiency action spectrum was obtained at this electrode. A very sharp peak around 725 nm, a low but constant quantum efficiency in the shorter wavelength region and an extended response to sub-band illumination were observed. These results suggest the formation of a surface layer with many impurity levels. AES and XPS depth profiling show that Ag diffuses deeper into the CdSe substrate than several tens of nanometers. The XPS study also suggests that Ag exists as Ag(0) in this layer. The junction characteristics of Au/CdSe and Au/CdSe(Ag) show that this layer has a very high resistance. PL measurements proved the introduction of high density impurity levels within this layer. On the basis of these results, a band model is presented for this electrode.

Analytical microscopy problems specific to highly divided solids

Analytical microscopy is very useful for characterizing highly divided solids, especially with the FEG-STEM which gives a high spatial resolution and a high intensity beam. Nanoscopic samplings are usually representative of the specimen. However, two main problems might be encountered: (i) the high level of impurities (adsorbed species) associated with the high surface area of these compounds; (ii) the change of composition due to enhanced diffusion of atoms under electron bombardment.

Moisture and Purity in Polyimide Coatings

Moisture and ionic impurities play a major role in the failure mechanism of integrated devices. [1] The use of organic polymers as microelectronic coatings offers advantages in improved planarization of metal steps, low temperature processibility, and reduction of mechanical stresses. [2] Cited disadvantages are the high inherent moisture absorption and level of impurities. Polymers introduce levels of moisture and impurities 10–100 times greater than vacuum deposited inorganic insulators.[3] Moreover, the combination of ionic impurities and a high humidity environment will degrade attractive polymer properties such as high resistivity and low dielectric constant. [4]

The Role of Arsine in Reducing Carbon in Triethylarsenic Grown GaAs Films

AbstractVery high carbon impurity levels (1018-1021cm−3) in GaAs films grown using triethylarsenic (Et3As) and trimethylgallium (Me3Ga) can be dramatically reduced by substituting a portion of the Et3As reagent with arsine during growth. Gallium arsenide epilayers grown at a deposition temperature of 560°C, a total V/III ratio =10, and the Group V reagent consisting of a mixture of Et3As and arsine, were found to exhibit carbon levels of only 5-7×1015cm−3for Group V mixtures ranging from 0-65% Et3As. All of these films were n-type, except for those grown using 100% arsine, which were p-type. The reduction in carbon incorporation in films grown using Et3As and arsine as co-reagents is shown to result from a unique, synergistic, reaction chemistry involving the two arsenic reagents. In particular, the decomposition of arsine to provide carbon-free, active arsenic fragments for growth is greatly enhanced by the presence of Et3As as a co-reactant.