Source Of Impurities Research Articles

Considerations and derivations of permitted daily exposure limits for impurities from intravitreal pharmaceutical products

Intravitreal (IVT) injection is an uncommon route of parenteral administration for therapeutic medications, but one of the most important for the treatment of ocular diseases, especially those related to macular degeneration. Nonetheless, there are currently no regulatory guidelines that specifically address how to establish a permitted daily exposure (PDE) for impurities and residual process reagents in IVT pharmaceutical drug products given the unique vulnerability of ocular tissues. The establishment of PDEs for IVT administration is complicated by the limited understanding of metabolism and clearance of small molecular weight chemicals from the human vitreous humor (VH), a problem compounded by the limited IVT-specific toxicological data. In this paper, we describe a feasible and comprehensive methodology for deriving PDE limits for impurities and residual process reagents from IVT drug products, as exemplified by five case studies, including inorganic elements, formic acid, polyethylene glycols, acetic acid, and caprolactam. The five case studies were selected to cover compounds with a wide range of impurity sources and toxicological data availability. The proposed framework considers both local ocular and systemic toxicity endpoints and advances the goal of a harmonized, science-based approach for deriving IVT PDE limits.

Charged Impurity Scattering and Electron-Electron Interactions in Large-Area Hydrogen Intercalated Bilayer Graphene.

Intercalation is a promising technique to modify the structural and electronic properties of 2D materials on the wafer scale for future electronic device applications. Yet, few reports to date demonstrate 2D intercalation as a viable technique on this scale. Spurred by recent demonstrations of mm-scale sensors, we use hydrogen intercalated quasi-freestanding bilayer graphene (hQBG) grown on 6H-SiC(0001), to understand the electronic properties of a large-area (16 mm2) device. To do this, we first analyze Shubnikov-de Haas (SdH) oscillations and weak localization, permitting determination of the Fermi level, cyclotron effective mass, and quantum scattering time. Our transport results indicate that at low temperature, scattering in hQBG is dominated by charged impurities and electron-electron interactions. Using low- temperature scanning tunneling microscopy and spectroscopy (STS), we investigate the source of the charged impurities on the nm-scale via observation of Friedel oscillations. Comparison to theory suggests that the Friedel oscillations we observe are caused by hydrogen vacancies underneath the hQBG. Furthermore, STS measurements demonstrate that hydrogen vacancies in the hQBG have an extremely localized effect on the local density of states, such that the Fermi level of the hQBG is only affected directly above the location of the defect. Hence, we find that the calculated Fermi level from SdH oscillations on the millimeter scale agrees with the value measured locally on the nanometer scale with STS measurements.

Sustainable organic waste valorisation: A zero-waste approach

The annual increase in global organic waste generation emphasises the need to develop a sustainable management platform to address environmental concerns. This study aims to explore sustainable treatments for the conversion of organic waste into energy in pursuit of zero-waste. The organic waste generated from the animal feed industry (referred to as WF) was used for the model compound in this study. 8.5 wt% of lipids were extracted from the WF, which contained unidentified impurities. Acid-catalysed transesterification yielded less than 80 wt% biodiesel might be due to the reversible reaction. In contrast, non-catalytic transesterification resulted in a significantly higher biodiesel yield (95.6 wt%), suggesting that this method was more effective at converting impure lipids into biodiesel compared to acid-catalysed transesterification. These results indicate the potential advantages of the non-catalytic approach, particularly when dealing with impure lipid sources. To minimise the generation of waste in the process, the WF residue produced after lipid extraction was converted into combustible gas (syngas) through pyrolysis. CO2 was used as a reactive medium in pyrolysis. In one-stage pyrolysis, the gas yield under CO2 was comparable to that under N2, indicating that CO2 did not react effectively with the volatiles derived from the WF residue. Enhanced CO2 reactivity was achieved via catalytic pyrolysis using a nickel-impregnated catalyst. Consequently, the combustible gas yield under CO2 was much higher than that under N2. This approach might contribute to maximising the efficiency of converting organic waste into renewable energy while simultaneously consuming CO2 during pyrolysis, thereby enhancing the sustainability of this approach.

Fabrication of Bipolar Membrane Electrolyzers for Seawater Electrolysis: Proof-of-Concept, Operando Design, and Fundamental Studies

Hydrogen (H2) is a critical industrial feedstock, essential in the production of fertilizer, steel, and fuels. Its demand is anticipated to increase ten-fold by 2050 due to its pivotal role in various new green technologies. Renewable energy-driven bipolar membrane water electrolyzers (BPMWEs) are a promising technology for sustainable production of H2 from seawater and other impure water sources. Here we present a detailed protocol on the assembly and operation of zero-gap membrane electrode assembly (MEA) BPMWE with water dissociation layers1. We describe steps for spray coating both electrodes and membranes, electrolyzer assembly, and electrochemical evaluation. This protocol provides an avenue to highlight key considerations in BPMWE fabrication methodology to ensure comparable data and rapid progress. We further highlight how this BPM platform can be used for a variety of scientific applications ranging from the seawater resistant BPMWE to an operando water electrolyzers to examine catalyst dynamics through X-ray absorption spectroscopy (XAS). As we work together towards a cleaner future, the detailed BPMWE protocol enables scientific communication, aiding in reproducible electrolyzer assembly practices, and accelerating the optimization of next-generation BPM-based devices.

Development and test of the laser blow-off impurity injection system in experimental advanced superconducting tokamak.

The Laser Blow-Off (LBO) impurity injection system is a crucial tool for studying impurity transport and plasma behavior. Conducting proactive impurity transport research is challenging on experimental advanced superconducting tokamak (EAST) due to the uncontrollable generation of impurity sources; therefore, it is necessary to develop a laser blow-off impurity injection system for injecting controlled trace impurity particles. This study presents the design and test results of an LBO system for the EAST. The system aims to provide precise and repeatable control over the timing and quantity of impurity injection. The system primarily consists of a laser source, two mirrors, a moveable focusing lens, a target material, and a vacuum system. The movement of the focusing lens is achieved by a three-dimensional displacement system. The operation of the system is completed by a remote control system. With the accurate control system, the laser spot diameter is adjustable, allowing for modification of impurity injection quantity. The test results demonstrate that the system can rapidly detect external trigger signals and ensure precise timing for the impurity injection. Furthermore, this system can also quickly change the focal point of the laser spot, addressing the requirements for impurity injections during the experiments with less than 0.4mm position error for laser spot focusing. Test results have shown that the aluminum film material can be peeled off by the LBO system when the laser energy exceeds 650 mJ and the smallest ablation spot is about 1mm. This study is of significant importance for conducting plasma impurity transport research on the EAST.

Aqueous alternating electrolysis prolongs electrode lifespans under harsh operation conditions

It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.

ICRH-related impurity source and control across experiments in H, D, T plasmas at JET-ILW

The experimental and theoretical analysis were focused on experiments conducted to assess the effect of plasma isotopes, protium (H), deuterium (D), and tritium (T) on ion cyclotron resonance heating (ICRH) related plasma wall interactions. Comparison of L-mode discharges with N = 1 3He and N = 1 H minority ICRH heating scenarios were done for different isotopes. For the selected pulses, the behaviour of high-Z, mid-Z and low-Z intrinsic impurity and radiated power behaviour was investigated based on data from VUV, visible spectroscopy, and bolometry diagnostic at Joint European Torus. It was found that for N = 1 3He scenario during radiofrequency antennas operation, core W, Ni content, Be source and the radiated power are higher for π/2 in comparison to dipole antenna phasing. Lowest core Ni, W content and radiated power is clearly observed for H plasmas in comparison to D and T, where for this ICRH scenario behaviour was similar. However, lower Be photon flux is observed for T in comparison to D plasmas. Be sputtering by He particles is responsible for such an effect. Additionally, several computer simulations were conducted using the COREDIV code. The difference in the electron temperature was due to the difference in the isotope masses. Increased temperature in the central plasma in the case of T plasmas leads to higher radiation in the central plasma in comparison to H plasmas. As a result, the power across separatrix is lower and the temperature on the divertor plate decreases with the increase of the isotope mass. At these temperatures on the divertor plate, W is not sputtered by the main plasma ions H, D and T and by He. For the N = 1 H ICRH scenario clear difference between D and T plasma was observed with higher metallic impurity content for T plasma in comparison to D. Impurity content in the plasmas is found to be sensitive to the power balance between the antenna straps. Its minimum is observed for the maximum of P cen/P tot.

Aerobic Oxidative Carboxylation of Styrene Over Cobalt Catalysts: Integrated CO2 Capture and Conversion.

The direct synthesis of cyclic carbonates through oxidative carboxylation of alkenes using CO2 and O2 offers a sustainable and carbon-neutral method for CO2 utilization, which is, however, still a largely unexplored field. Here we develop a single-atom catalyst (SAC) Co-N/O-C as the earth-abundant metal catalyst for the oxidative carboxylation of styrene with CO2 and O2. Remarkably, even using the flue gas as an impure CO2 and O2 source, desired cyclic carbonate could be obtained with moderate productivity, which shows the potential for integrated CO2 capture and conversion, leveraging the high CO2 adsorption capacity of Co-N/O-C. In addition, the catalyst can be reused five times without an obvious decline in activity. Detailed characterizations and theoretical calculations elucidate the crucial role of single Co atoms in activating O2 and CO2, as well as controlling selectivity.

Recent Approaches of Impurity Profiling in Pharmaceutical Analysis: A Concise Review

Purity profiling is the process of gathering and analyzing information to determine the biological safety of a specific impurity, hence highlighting its importance and range in pharmaceutical research. In the field of pharmaceuticals, impurity has no precise meaning. Identification, structural elucidation, and quantitative determination of impurities and degradation products in bulk medicinal materials and pharmaceutical formulations are all included in impurity profiling. Since unrecognized, possibly poisonous impurities are dangerous to health and should be found and determined by selective procedures in order to increase the safety of drug therapy, impurity profiling has become more significant in contemporary pharmaceutical analysis. Impurities are typically described using words like residual solvents, byproducts, transformation products, degradation products, interaction products, and related products. Impurity identification is carried out using different chromatographic methods in addition to passing the CGMP, QC, QA, and water activity tests, a pharmaceutical ingredient also needs to satisfy the requirements for a new impurity. It is important to separate and characterize impurities in order to collect and evaluate data that determines biological safety, which emphasizes the need for and promise of drug impurity profiling in pharmaceutical research. To separate and measure the pollutants, a range of instrumental analytical techniques have been consistently used. The detection and regulatory evaluation of organic impurities is a very challenging task because to the numerous sources of organic impurities, including microbiological contamination, API breakdown products, and traces of intermediates.

Accumulation and removal of Si impurities on β-Ga2O3 arising from ambient air exposure

Here, we report that a source of Si impurities commonly observed on (010) β-Ga2O3 is from exposure of the surface to air. Moreover, we find that a 15 min hydrofluoric acid (HF) (49%) treatment reduces the Si density by approximately 1 order of magnitude on (010) β-Ga2O3 surfaces. This reduction in Si is critical for the elimination of the often observed parasitic conducting channel, which negatively affects transport properties and lateral transistor performance. After the HF treatment, the sample must be immediately put under vacuum, for the Si fully returns within 10 min of additional air exposure. Finally, we demonstrate that performing a 30 min HF (49%) treatment on the substrate before growth has no deleterious effect on the structure or on the epitaxy surface after subsequent Ga2O3 growth.

Full-radius integrated modelling of ASDEX Upgrade L-modes including impurity transport and radiation

An integrated framework that demonstrates multi-species, multi-channel modelling capabilities for the prediction of impurity density profiles and their feedback on the main plasma through radiative cooling and fuel dilution is presented. It combines all presently known theoretical elements in the local description of quasilinear turbulent and neoclassical impurity transport, using the models TGLF-SAT2 and FACIT. These are coupled to the STRAHL code for impurity sources and radiation inside the ASTRA transport solver. The workflow is shown to reproduce experimental results in full-radius L-mode modelling. In particular, a set of ASDEX Upgrade L-modes with differing heating power mixtures and plasma currents are simulated, including boron (B) and tungsten (W) as intrinsic impurities. The increase of predicted confinement with higher current and the reduction of core W peaking with higher central wave heating are demonstrated. Furthermore, a highly radiative L-mode scenario featuring an X-point radiator (XPR) with two intrinsic (B, W) and one seeded argon (Ar) species is simulated, and its measured radiated power and high confinement are recovered by the modelling. The stabilizing effect of impurities on turbulence is analysed and a simple model for the peripheral X-point radiation is introduced. A preliminary full-radius simulation of an H-mode phase of this same discharge, leveraging recent work on the role of the E×B shearing at the edge, shows promising results.

Distribution of Iron and Boron Between Silicon Metal Smelting Products in Industrial Saf using Borate Fluxes

The article identifies the key sources of iron and boron impurities entering silicon metal under industrial smelting conditions in Submerged arc furnace (SAF). Impurity rocks in the composition of quartz, the main raw material for the production of silicon metal, were studied using the X-ray fluorescence method, and their visual classification was carried out. It has been established that the energy of secondary characteristic x-ray radiation (CXR) for boron and iron contained in the feedstock is 3.1 and 6.3 keV, respectively. A relationship was found between the intensity of CXR pulses and the concentration of iron and boron impurities. The features of the distribution of these elements between metallurgical phases (silicon metal, slag and gas phase) when used in the smelting process with and without borate flux (colemanite) have been established. Under industrial conditions, it has been established that the transfer coefficient of boron into silicon metal is reduced when using borate flux from 76.3% to 58.36%. The transfer of iron into silicon metal from the charge remains at the same level with a slight downward trend from 93.18% to 92.12%. This may be explained by a reduction in the contact time of the molten slag accumulating on the bottom with liquid silicon metal. There is also a reduction in the consumption of charge materials when using colemanite from 6.07 to 5.635 t/t of silicon metal due to the reduction in the time of cleaning the smelting bath from viscous slag accumulated on the bottom.

3D radiated power analysis of JET SPI discharges using the Emis3D forward modeling tool

Precise values for radiated energy in tokamak disruption experiments are needed to validate disruption mitigation techniques for burning plasma tokamaks like ITER and SPARC. Control room analysis of radiated power (P rad) on JET assumes axisymmetry, since fitting 3D radiation structures with limited bolometry coverage is an under-determined problem. In mitigated disruptions, radiation is toroidally asymmetric and 3D, due to fast-growing 3D MHD modes and localized impurity sources. To address this problem, Emis3D adopts a physics motivated forward modeling (‘guess and check’) approach, comparing experimental bolometry data to synthetic data from user-defined radiation structures. Synthetic structures are observed with the Cherab modeling framework and a best fit chosen using a reduced χ 2 statistic. 2D tomographic inversion models are tested, as well as helical flux tubes and 3D MHD simulated structures from JOREK. Two nominally identical pure neon shattered pellet injection (SPI) mitigated discharges in JET are analyzed. 2D tomographic inversions with added toroidal freedom are the best fits in the thermal quench (TQ) and current quench (CQ). In the pre-TQ, 2D reconstructions are statistically the best fits, but are likely over-optimized and do not capture the 3D radiation structure seen in fast camera images. The next-best pre-TQ fits are helical structures that extend towards the high-field side, consistent with an impurity flow under the magnetic nozzle effect also observed in JOREK simulations. Whole-disruption radiated fractions of 0.98+0.03/ −0.29 and 1.01+0.02/−0.17 are found, suggesting that the stored energy may have been fully mitigated by each SPI, although mitigation efficiencies well below ITER and SPARC requirements for high energy pulses are still within the large uncertainties. Emis3D is also used to validate JOREK SPI simulations, and confirms improvements in matching experiment from changes to impurity modeling. Time-dependent toroidal peaking factors are calculated and discussed.

Hyaluronan: Sources, Structure, Features and Applications.

Hyaluronan (HA) is a non-sulfated glycosaminoglycan that is present in a variety of body tissues and organs. Hyaluronan has a wide range of biological activities that are frequently influenced by molar mass; however, they also depend greatly on the source, purity, and kind of impurities in hyaluronan. High-molar-mass HA has anti-inflammatory, immunosuppressive, and antiangiogenic properties, while low-molar-mass HA has opposite properties. A number of chemical modifications have been performed to enhance the stability of HA and its applications in medical practice. Hyaluronan is widely applied in medicine, such as viscosupplementation, ophthalmology, otolaryngology, wound healing, cosmetics, and drug delivery. In this review, we summarized several medical applications of polymers based on the hyaluronan backbone.

Hydrogen quality in used natural gas pipelines: An experimental investigation of contaminants according to ISO 14687:2019 standard

The transport of hydrogen in used natural gas pipelines is a strategic key element of a pan-European hydrogen infrastructure. At the same time, accurate knowledge of the hydrogen quality is essential in order to be able to address a wide application range. Therefore, an experimental investigation was carried out to find out which contaminants enter into the hydrogen from the used natural gas pipelines. Pipeline elements from the high pressure gas grid of Austria were exposed to hydrogen. Steel pipelines built between 1960 and 2018, which were operated with odorised and pure natural gas, were examined. The hydrogen was analysed according to requirements of ISO14687: 2019 Grade D measurement standard. The results show that based on age, odorization and sediments, different contimenants are introduced. Odorants, hydrocarbons but also sulphur compounds, ammonia and halogenated hydrogen compounds were identified. Sediments are identified as the main source of impurities. However, the concentrations of the introduced contaminants were low (6 nmol/mol to 10 μmol/mol). Quality monitoring with a wide range of detection options for different components (sulphur, halogenated compounds, hydrocarbons, ammonia and atmospheric components) is crucial for real operation. The authors deduce that a Grade A hydrogen quality can be safely achieved in real operation.

The Elemental Composition of Hemp Flower: Sources of Elemental Impurities and Implications for Consumer Product Safety

The Elemental Composition of Hemp Flower: Sources of Elemental Impurities and Implications for Consumer Product Safety

Narrowband photoluminescence of Tin-Vacancy colour centres inSn-doped chemical vapour deposition diamond microcrystals.

Tin-Vacancy (Sn-V) colour centres in diamond have a spin coherence time in the millisecond range at temperatures of 2 K, so they are promising to be used in diamond-based quantum optical devices. However, the incorporation of large Sn atoms into a dense diamond lattice is a non-trivial problem. The objective of our work is to use microwave plasma-assisted chemical vapour deposition (CVD) to grow Sn-doped diamond with submicron SnO2 particles as a solid-state source of impurity. Well-faceted diamond microcrystals with sizes of afewmicrometres were formed on AlN substrates. The photoluminescence (PL) signal with zero-phonon line (ZPL) peak for Sn-V centre at ≈620 nm was measured at room temperature (RT) and at 7 K. The peak width (full width at half-maximum) was measured to be 1.1-1.7 nm at RT and ≈0.05 nm at 7 K. The observed variations of ZPL shape and position, in particular, narrowing of PL peak at RT and formation of single-line fine structure at low-T, are attributed to strain in the crystallites. The diamond doping with Sn via CVD process offers a new route to from Sn-V colour centre in the bulk of the diamond crystallites. This article is part of the Theo Murphy meeting issue 'Diamond for quantum applications'.

Characterization of early current quench time during massive impurity injection in JT-60SA

Characteristics of the early current quench (CQ) time in mitigated disruptions are studied for a full-current (5.5 MA) scenario in the JT-60SA superconducting tokamak. Self-consistent evolution of the plasma temperature and current density profiles during the early CQ phase before the plasma moves vertically is simulated using the axisymmetric disruption code INDEX for given impurity source profiles. It is shown that the hollow (flat) impurity density profiles peaks (flattens) the current density, and it causes a temporal change in the internal inductance in this phase. However the resultant CQ time is found to be insensitive to the impurity source profile for the same assimilated quantity. The simulation results are interpreted by the L/R model including the temporal change in the internal inductance as well as the effect of a gap between the plasma and the conducting vessel structures and stabilizing plates. This results will improve the accuracy to estimate the amount of impurity assimilated into plasma from the observed CQ rate in the massive gas injection (MGI) experiment planned in JT-60SA. The accessible range in which the CQ time can be scanned as well as the electron densities to suppress runaway electrons is also shown for different injected amounts of neon, argon, and their deuterium mixture under the limitation of the MGI gas amount. Mitigated disruptions in JT-60SA typically lead to the CQ time shorter than the vessel wall time, which is expected to produce relevant contributions to disruption mitigation in ITER and future reactors.

Nitrosamine impurities in pharmaceutical dosage forms: Current challenges and mitigation strategies

Nitrosamine impurities have been detected in various pharmaceutical products in nowadays. These impurities are classified as probable human carcinogens and can be found in a wide range of products including pharmaceuticals, industrial chemicals and food. This review paper provides a comprehensive analysis of nitrosamine impurities in Pharmaceutical dosage forms. It covers the formation and sources of nitrosamine impurities, allowable daily intake impurities limit (ng/day), the analytical methods employed for their detection. Various methods including LC-MS, GC-MS and HPLC for nitrosamine impurities, regulatory guidelines, notable incidents, case studies and the impact of nitrosamine impurities contamination on the pharmaceutical landscape and additionally, case studies of previous incidents involving nitrosamine-contaminated pharmaceutical products. Furthermore, this overall review provides outlines the current mitigation strategies, risk assessment, future directions and challenges adopted by pharmaceutical companies to ensure Drug safety and regulatory compliance in worldwide also provides a comprehensive examination of the current state of knowledge regarding nitrosamine impurities in pharmaceutical dosage forms.

Dimensionality of executive functions and processing speed in preschoolers

Processing speed is a foundational cognitive ability strongly associated with executive functions in children. To precisely interpret children's results in measures of executive functions, it is important to identify variation that is due to differences in executive functions versus processing speed. In this study, we examined the dimensionality of executive functions and processing speed in 3–6 years old preschoolers over six months with two time points. Executive functions and processing speed (i.e., choice reaction time) were assessed using computer-based tests.Confirmatory factor analyses showed that executive functions and processing speed were divided into two dimensions (processing speed+inhibition+switching and updating) at both time points. Regarding executive functions, the findings indicate that in preschoolers, inhibition+switching is inseparable, but updating is separable from processing speed. Findings emphasize the need to critically evaluate the underlying characteristics of different executive function tasks to better understand the development of executive function and its associations with other cognitive and academic skills. Educational relevance statementIn this study, we examined dimensionality of executive functions and processing speed in preschoolers. Executive functions have been identified as important predictors for school readiness and later academic performance. To better understand individual differences in executive functions and their associations with other cognitive and academic skills in early childhood, accurate measures of executive functions are needed. However, there has been concern that other cognitive processes involved in performing various EF tasks might mask variation in executive functions proficiency. Processing speed is one potential source of measurement impurity in measures of executive functions. However, the evidence about the dimensionality of executive functions and processing speed among young children is limited. To precisely interpret the children's results in measures of executive functions, it is important to identify variation that is due to differences in executive functions versus processing speed.