Accelerated Stress Conditions Research Articles

Inorganic Compound and Cycloserine Composite Particles for Improved Stability

The aim of this study was to improve the chemical stability of cycloserine containing organic and inorganic compounds. Composite particles were manufactured with a 1:1 weight ratio of organic/inorganic compounds and cycloserine. The influence of organic/inorganic compounds on the stability of cycloserine was investigated under accelerated stress conditions at 60°C/75% RH for 24 hours. In addition, the properties of the composite particles were evaluated using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and the dissolution of the drug was assessed by preparing it as a hard capsule. Among the organic and inorganic compounds investigated, calcium hydroxide most improved the stability of cycloserine under accelerated stress conditions (53.3 ± 2.2% vs 1.7 ± 0.2%). DSC results confirmed the compatibility between calcium hydroxide and the cycloserine, and SEM results confirmed that it was evenly distributed around the cycloserine. Calcium hydroxide also showed more than 90% cycloserine dissolution within 15 minutes. Therefore, the calcium hydroxide and cycloserine composite particles may be candidates for cycloserine oral pharmaceuticals with enhanced drug stability.

Residual Life Prediction of Low-Voltage Circuit Breaker Thermal Trip Based on the Wiener Process

A low-voltage circuit breaker thermal trip plays a role in power systems, including opening and closing, control, protection, and more. Their reliability directly affects the security and stability of the power distribution system. The Wiener process model is established according to the accelerated degradation data of thermal trips, and remaining life prediction is carried out. In this paper, firstly, the constant stress accelerated degradation test is carried out on a thermal trip with temperature as the accelerated stress and specific thermal deflection as the degradation eigenquantity to characterise the degradation trajectory according to the degradation data and analyse the degradation law; then, it is verified by the test of normal distribution that the degradation data of the thermal trip conform to the Wiener process. The Wiener process, using the great likelihood estimation method to estimate the parameters of the remaining life, calculates the remaining life probability density function and reliability function under different temperature stresses and obtains the remaining life of the thermal trip under each accelerated stress conditions; finally, the remaining life of the thermal trip at the initial moment is taken as the pseudo-failure life, and the Arrhenius accelerated model is utilised to launch the external thermal trip under normal stress. Finally, the Arrhenius acceleration model is used to extrapolate the lifespan of the thermal trip under normal stress.

Cyclic stress accelerated life test method for mechatronic products

AbstractThe reliability requirements for mechatronics continue to increase. Traditional life test methods make it difficult to obtain the data required to assess or predict the reliability of these mechatronic products within a reasonable time. Accelerated life tests can speed up the failure process of the product by using accelerated stress conditions. And then test data is obtained to predict the reliable life of the product under normal service conditions through modeling and analysis. The test efficiency of the accelerated life tests is higher than that of the life test. So, the method of accelerated life tests has become a solution for life and reliability prediction of highly reliable and long‐life mechatronic products. However, mechatronic products usually undergo cyclic stress during service. The use of cyclic stress as an accelerating stress in accelerated life tests can provide a realistic representation of service conditions and achieve higher test efficiency. Cyclic stress accelerated life test is an accurate and efficient solution for predicting the life and reliability of such mechatronic products. Current relative research is focused on constant stress, step stress and sequential stress accelerated life tests. A great challenge in engineering is modeling and analysis of cyclic stresses accelerated life tests. In this paper, we first describe the cyclic stress accelerated life test profile and its key parameters, then propose model assumptions and establish a modelling and analysis method for cyclic stress accelerated life test data, followed by an illustrative example to apply and validate the proposed method. The research results can provide technical support for the life and reliability assessment of mechatronic products under cyclic stress service conditions.

Accelerated constant current stress on triple cation perovskite solar cells

The increasing demand for renewable and cost-effective energy sources requires not only the development of alternative solar technologies, but these new technologies must be stable enough to be used in a real-life application. For this reason, perovskite solar cells (PSCs) must be investigated not only in terms of power conversion efficiency, but also in terms of reliability. In this work, accelerated forward current stress is applied as a tool to investigate PSCs stability and degradation kinetic emulating real-life scenarios. The choice of the hole-blocking layer (HBL) plays a crucial role in PSCs intrinsic instability as well as in their degradation rate, which follows a stretched exponential law. Here, tin oxide (SnOX) and bathocuproine (BCP) are investigated as HBLs observing that for low stress currents BCP-based PSCs degrade faster than SnOX-based PSCs, whereas for large stress currents SnOX-based PSCs degrade faster than BCP-based PSCs. The results also indicated that the major cause of degradation in the devices is primarily driven by the formation of shunt paths leading to cell breakdown. Our findings offer valuable insights for improving the stability of PSCs under accelerated stress conditions and provide useful information for the design of PSC-based solar panels depending on their field of applications.

Chemometrics in Protein Formulation: Stability Governed by Repulsion and Protein Unfolding.

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.

Sulfonated Poly(Phenylene sulfone) blend membranes finding their way into proton exchange membrane fuel cells

We demonstrate performance and durability of a fluorine-free poly(phenylene-sulfone) membrane for proton exchange membrane fuel cells. Sulfonated poly(phenylene-sulfone) (EW 220 g·eq−1; sPPS-220) has been prepared and processed by acid/base blending with 25 wt% poly(benzimidazole) (sPPS-220/PBI-O). A blend membrane with a nominal EW 463 g·eq−1(ion exchange capacity of 2.16 meq·g−1) has been fabricated by solution co-casting on a commercial production line. Blend component fractions are chosen to meet Nafion 211's specific conductivity and obtain mechanical robustness. Blend membrane has significantly lower gas permeability than Nafion under both dry (RH = 30%) and wet (RH = 95%) conditions, significantly higher storage modulus and no softening at high temperature. Like pure-sPPS, blend membrane is hydrolytically stable up to T = 180 °C in water. Single-cell H2/air fuel cell tests demonstrate higher open-circuit voltage and similar performance under load conditions compared to Nafion. Still, high mass transport polarization is likely due to water condensation at the cathode side. This increases membrane swelling and thus electroosmotic water drag reducing hydration at the anode side and leading to flooding of the cathode. Under accelerated stress conditions at low relative humidity, sPPS-220/PBI-O is more durable than Nafion. Possible explanations are i) lower gas crossover reduced radical formation rate and ii) high intrinsic stability of sPPS.

A universal multi-additive strategy to enhance efficiency and stability in inverted perovskite solar cells

Perovskite solar technology has become a trend topic in the last decade, reaching promising efficiencies up to 25.7 %. Researchers mainly focused on obtaining high performance rather than caring for stability under accelerated stress conditions, such as thermal and light soaking tests. For this reason, we studied a standard triple cation perovskite (∼1.58 eV) and wider bandgap perovskite (∼1.63 eV) with the scope of finding a common strategy to build a robust device stable over time independently of the perovskite used. We use a combination of additives inside the perovskite ink: ionic liquid 1-Butyl-3-methylimidazolium tetrafluoroborate (BMIM-BF4), alkylamine ligands oleylamine (OAm) and benzylhydrazine hydrochloride (BHC). Our work reveals that the combination of these additives helps to improve the efficiency and stability of the entire device, reaching a power conversion efficiency up to 21.3 % and over 20 % for both types of perovskite and stability beyond 1000 h under continuous light soaking. The universal applicability of this method was further applied to a robust methylammonium free perovskite, leading to an impressive stability both under light soaking and under 85 °C, showing T90 > 1500 h and T80 > 8658 h, respectively: the solar cells modified with the additive mixture retained 95 % of their efficiency after 1000 h under light soaking at 45 °C and 100 % of their efficiency after 1500 h of stress at 85 °C.

High Temperature Polymer Electrolyte Membrane Fuel Cells with High Phosphoric Acid Retention

Phosphoric acid loss poses immense hurdles for the durability of high-temperature polymer electrolyte membrane fuel cells (HT-PEMFCs). Here we report quaternary ammonium-biphosphate ion-pair HT-PEMFCs that do not lose phosphoric acids under normal and accelerated stress conditions. Our energetics study explains the acid loss behavior of the conventional phosphoric acid-polybenzimidazole (PA-PBI) system by two mechanisms. If PA loss occurs via acid evaporation, the acid loss is constant over time. On the other hand, when water activity in the PA-PBI system is high, exponential decay of PA loss occurs via the water replacement mechanism. Combined 31P NMR and computational studies show that the proposed ion-pair system has six times higher interaction energy, which allows for containing all PAs in the membrane electrode assemblies under a broad range of operating conditions. In addition, polar interactions between the phosphonic acid ionomer and phosphoric acid explain acid retention in the electrodes of the ion-pair HT-PEMFCs.

Visualization of Combustion in Polymer-Electrolyte-Membrane Fuel Cell - Mechanism on Abrupt Change from Moderate to Accidental Scale-

This study is focused on elucidating the catalytic combustion phenomenon in proton-exchange membrane fuel cells. A visualization cell and an infrared (IR) camera are used to capture the thermal behavior under combined chemical and mechanical accelerated stress conditions in situ. A 3.4 cm2 catalyst coated membrane (CCM) embedded in the cell is subjected to a relative humidity (RH) cycling test at atmospheric pressure and a cell temperature of 80 °C under open-circuit voltage (OCV) conditions. The temperature distribution on the gas diffusion layer surface at the cathode is captured using a high-transmittance glass window (ZnS window). Continuous IR imaging revealed a hot spot at ca. 500 RH cycles, suggesting the existence of a pinhole in the degraded CCM and the occurrence of catalytic combustion there. The occurrence of the hot spot coincides with the time at which the electrochemical indicators detect membrane failure, i.e., hydrogen crossover rate, OCV. Furthermore, the post mortem analysis revealed a 105-micrometer diameter pinhole, the position of which matched that of the hotspot. An accidental combustion during the durability test could cause the formation of a pinhole. This pinhole is responsible for the rapid increase in the hydrogen crossover rate as well as the significant decrease in the OCV at 500 RH cycles until the end of the durability test. Figure 1

Spray-drying Microencapsulation of an Extract from Tilia tomentosa Moench Flowers: Physicochemical Characterization and in Vitro Intestinal Activity

Silver linden (Tilia tomentosa Moench, TtM) flowers possess several health-promoting properties, especially at the neurological level, such as intestinal relaxation activity associated with specific flavonols, particularly quercetin and kaempferol derivatives. However, such molecules are susceptible to degradation upon different triggers like heat, light and extreme pH values. To overcome the scarce stability of TtM flowers bioactive molecules and make them suitable for developing functional food and supplements, we applied microencapsulation. Spray-drying microencapsulation of TtM flowers extract was performed using three starch-derived wall materials: maltodextrin 12 DE (MD12) and 19 DE (MD19), and OSA-modified starch (OSA-S). The stability of total phenols, flavanols, and antioxidant capacity was monitored for 70 days under accelerated stress conditions (40 °C/70% RH) by HPLC and spectrophotometric methods, and the intestinal contractile activity was tested in a murine model. In comparison to MD12 and MD19, OSA-S stood out for the higher encapsulation efficiency of quercetin and kaempferol glycosides (+ 36–47% compared to MD12 and + 18–24% compared to MD19) and stability thereof (half-life on average + 30% compared to MD12 and + 51% compared to MD19). The intestinal contractile activity of OAS-S powders resulted comparable to the original extract, indicating that flavonols were biologically active and accessible. Our results underly the potential advantages of OSA-S encapsulated formulation as a functional ingredient for the development of nutraceutical products.

Investigation of in-situ catalytic combustion in polymer-electrolyte-membrane fuel cell during combined chemical and mechanical stress test

This study is focused on elucidating the catalytic combustion phenomenon in proton-exchange-membrane fuel cells. A visualization cell and an infrared (IR) camera are used to capture the thermal behavior under combined chemical and mechanical accelerated stress conditions in situ. Catalyst coated membrane (CCM) embedded in the cell is subjected to a relative humidity (RH) cycling test under open-circuit voltage (OCV) conditions at atmospheric pressure and at a cell temperature of 80 °C. The temperature distribution on the gas diffusion layer surface at the cathode is captured through a high-transmittance glass window (ZnS window). Continuous IR imaging revealed a hot spot at ca. 500 RH cycles, suggesting the existence of a pinhole in the degraded CCM and the occurrence of catalytic combustion there. The occurrence of the hot spot coincides with the time at which the electrochemical indicators detect membrane failure, i.e., hydrogen crossover rate, OCV. Furthermore, a post mortem analysis revealed a 105-μm diameter pinhole, the position of which matched that of the hot spot. This pinhole is responsible for the rapid increase in the hydrogen crossover rate as well as the significant decrease in the OCV at 500 RH cycles until the end of the durability test.

Life decay characteristics identification method of retired power batteries based on inverse power law model of accelerated life test

In order to reduce the sorting complexity of retired power batteries, the life decay characteristics identification method of power battery module based on the accelerated life test is proposed in the paper. Firstly, the influence of different parameters (environmental temperature, charge–discharge depth, charge–discharge rate, etc.) on the life decay of single battery is analyzed according to the historical data of retired power batteries. The main parameters affecting the life decay of power battery are determined. Secondly, the correlation characteristic function between terminal voltage, state of charge (SOC) of single battery and state of health (SOH) of battery module is established. The accelerated stress conditions suitable for retired power battery module is selected for accelerated life test. Finally, the attenuation characteristics of retired battery module are characterized by accelerated life test, which provided theoretical support for the rapid and accurate echelon utilization of power batteries.

Mechanistic understanding of metal-catalyzed oxidation of polysorbate 80 and monoclonal antibody in biotherapeutic formulations

Surfactants are commonly used in biotherapeutic formulations to prevent the formation of aggregates and protect proteins from denaturation. Among them polysorbates are the most widely used. However, they are known to be prone to degradation, mainly via enzymatic hydrolysis and oxidation.In this study, the impact of different conditions and factors on the oxidation of polysorbate 80 (PS80) and of a monoclonal antibody (mAb) was evaluated. In particular, the role of different formulation components (e.g., mAb concentration, pH, buffer, surfactant grade, chelators) was investigated in the presence of iron as transition metal contaminant.The results of our studies demonstrated that PS80 oxidation was accelerated even in the presence of iron levels as low as 20 ppb. In addition, the results showed that the oxidation of a specific solvent-exposed mAb methionine increased with PS80 oxidation, in particular under accelerated stress conditions and that the oxidation phenomenon was hindered in absence of iron or after addition of EDTA. Our results showed that PS80 “all oleate” (PS80-AO) was more sensitive to oxidative degradation than PS80 “multi-compendial” (PS80-MC). Contrary to acetate and citrate buffers, the results showed that the kinetics of PS80 oxidation was pH-dependent in presence of histidine buffer. It was also demonstrated that, when increasing its concentration, the mAb exhibited a protective effect against metal catalyzed PS80 and methionine oxidation.Our systematic studies on the role of the formulation components and potential contaminants (i.e., iron) demonstrated the complexity of the oxidative mechanism and the importance of different competitive systems, including pro-oxidant factors (e.g., iron, pH, PS80 quality) and antioxidant factors (e.g., protein concentration, EDTA, citrate) that may occur in biologic formulations containing PS80.

Flexible time reduction method for burn‐in of high‐quality products

AbstractBurn‐in is an effective method to screen out early failures of electronic devices. Typically, this is achieved by operating the devices under accelerated stress conditions. This paper focuses on a burn‐in concept where a random sample of devices is drawn out of the running production, put to burn‐in, and investigated for early failures. This procedure is called burn‐in study. In parallel, as long as the burn‐in study is ongoing, all other produced devices are subjected to burn‐in screening. In this article, new flexible sampling plans for burn‐in studies are introduced. These are based on the progress of these studies and defined quality targets. Furthermore, these sampling plans enable fast burn‐in time reductions and various time reduction strategies. From a statistical point of view, this requires to combine the proportion of early failures in a population with their lifetime distribution function. The new model is illustrated by case studies and simulations. It contributes to burn‐in cost reductions, while controlling quality levels at the same time.

Demonstration of CMOS-Compatible Multi-Level Graphene Interconnects With Metal Vias

Doped-multilayer-graphene (DMLG) interconnects employing the subtractive-etching (SE) process have opened a new pathway for designing interconnects at advanced technology nodes, where conventional metal wires suffer from significant resistance increase, self-heating (SH), electromigration (EM), and various integration challenges. Even though single-level scaled graphene wires have been shown to possess better performance and reliability with respect to dual-damascene (DD) and SE-enabled metal wires, a multi-level graphene interconnect technology (with vias) has remained elusive, which is of paramount importance for its integration in future technology nodes. This work, for the first time, addresses that need by engineering a CMOS-compatible solid-phase growth technique to yield large-area multilayer graphene (MLG) on dielectric (SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) and metal (Cu) substrates and subsequently demonstrating multi-level MLG interconnects with metal vias. Using rigorous theoretical and experimental analyses, we demonstrate that multi-level MLG interconnects with metal vias undergo <; 2% change in the via resistance under accelerated stress conditions, demonstrating its superior reliability against SH and EM, making them ideal candidates for sub-10 nm nodes.

Novel dissolving microneedles preparation for synergistic melasma therapy: Combined effects of tranexamic acid and licorice extract

The aim of this study was to prepare dissolving microneedles (DMNs) patches containing tranexamic acid (TA) for the treatment of melasma. Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) were preferred as matrix materials through the compatibility experiment. In the in vitro permeation study, the transdermal amount of TA was significantly promoted through dissolving microneedles with the cumulative release was 44.43 ± 6.55%. By comparison, the release of TA solution assisted with solid microneedles (SMNs) was merely 11.31 ± 2.30% (p < 0.05). Pharmacokinetics study indicated the bioavailability of dissolving microneedles was more than 1.3 times compared with oral administration. In pharmacodynamics investigation, TA dissolving microneedles obviously reduced melanin deposition in the skin of melasma guinea pigs after 8 consecutive administrations. In particular, the combination of tranexamic acid and licorice extract (LIC) dissolving microneedles worked better than tranexamic acid alone. Accelerated stress conditions including high temperature, high humidity, as well as photostability were designed to prove that TA microneedles maintained good pharmaceutical stability. In conclusion, tranexamic acid dissolving microneedles showed reliable quality and remarkable effect. Moreover, the combination of tranexamic acid and licorice extract had a synergistic therapy in melasma.

ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

A unified aging compact model for hot carrier degradation under mixed-mode and reverse E-B stress in complementary SiGe HBTs

This paper presents an accurate, comprehensive and physics-based aging compact model for stress-induced degradation due to hot-carrier generation and oxide trapping in advanced complementary NPN and PNP SiGe HBTs. The analytical model equations are derived from the solution of reaction–diffusion theory and Fick’s law of diffusion combined with oxide trapping mechanism under accelerated stress conditions. The model accuracy has been validated against results from long-term aging tests performed close to the safe-operating-areas of an advanced complementary 0.25 µm BiCMOS technology. Degradation asymmetry observed between NPN and PNP devices is accurately captured by this unified aging compact model. This study highlights the challenges of predicting degradation of complementary circuits and thereby improving its functionalities by designing better-matched NPN and PNP HBTs.

Separate quantification of anastrozole and letrozole by a novel stability‐indicating ultra‐fast LC method

AbstractA unified stability‐indicating method has been proposed using standardized ultra‐fast liquid chromatography conditions applicable to quantification of both anastrozole and letrozole in low dose pharmaceutical tablets. The drugs were subjected to chromatography one at a time following forced degradation at accelerated stress conditions. Separation of the main analyte from the possible degradation products was achieved on a Waters Aquity BEH C18 (50 × 2.1 mm; 1.7 µm) column maintained at 40°C with gradient elution of mobile phase comprising solvent A (0.1% orthophosphoric acid and acetonitrile [70:30 v/v]) and solvent‐B (0.1% orthophosphoric acid and acetonitrile [30:70 v/v]) at a flow rate of 0.35 mL/min. Photo diode array detection of anastrozole and letrozole was made at 215 and 236 nm, respectively. The stress testing demonstrated that both the drugs are susceptible to degrade by base hydrolysis and oxidation. The method was also applied for cleaning validation (residue analysis) at 0.5 µg with a limit of quantification &gt; 10 S/N for 0.1 µg of both drugs. The recovery assessed on two different surfaces of cGMP area (Stainless steel and Class‐A Glass) was satisfactory.

Impact of Highly Stable Catalyst Support Materials on Polymer Electrolyte Membrane Fuel Cell Performance

Durability of catalyst support materials is one of the big challenges for long‐term fuel cell operation. The performance stabilities of stabilized carbons as cathode catalyst supports for polymer electrolyte membrane fuel cells (PEMFCs) are investigated. Homemade platinum (Pt) electrocatalysts are prepared on stabilized carbons and a traditional carbon black support. Subsequently, the characterization results of homemade catalysts are compared with a commercial catalyst. The characterization tools such as the measurement of electrochemical active surface areas (ECSAs), oxygen reduction reaction (ORR) activities, durability of both the Pt and the supports, and eventually membrane electrode assembly (MEA) single cell tests are implemented herein. The stabilized carbon supported catalysts show comparable ORR activities as well as improved corrosion resistance in terms of ECSA survival rates under accelerated stress conditions compared with the conventional supported catalysts. In addition, the dependency of MEA performances on the ionomer‐to‐carbon ratio on the catalyst layers is established.