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The in vitro release study is a critical test to assess the safety, efficacy, and quality of nanoparticle-based drug delivery systems, but there is no compendial or regulatory standard. The variety of testing methods makes direct comparison among different systems difficult. We herein proposed a novel sample and separate (SS) method by combining the United States Pharmacopeia (USP) apparatus II (paddle) with well-validated centrifugal ultrafiltration (CU) technique that efficiently separated the free drug from nanoparticles. Polymeric drug nanoparticles were prepared by using a four-stream multi-inlet vortex mixer with d-α-tocopheryl polyethylene glycol 1000 succinate as a stabilizer. Itraconazole, cholecalciferol, and flurbiprofen were selected to produce three different nanoparticles with particle size <100 nm. By comparing with the dialysis membrane (DM) method and the SS methods using syringe filters, this novel SS + CU technique was considered the most appropriate in terms of the accuracy and repeatability to provide the in vitro release kinetics of nanoparticles. Interestingly, the DM method appeared to misestimate the release kinetics of nanoparticles through separate mechanisms. This work offers a superior analytical technique for studying in vitro drug release from polymeric nanoparticles, which could benefit the future development of in vitro-in vivo correlation of polymeric nanoparticles.

As one of the most promising new energy sources, the lithium-ion battery (LIB) and its associated safety concerns have attracted great research interest. Herein, a comprehensive review on the thermal hazards of LIBs and the corresponding countermeasures is provided. In general, the thermal hazards of the LIB can be caused or aggravated by several factors including physical, electrical and thermal factors, manufacturing defect and even battery aging. Due to the activity and combustibility of traditional battery components, they usually possess a relatively high thermal hazard and a series of side reactions between electrodes and electrolytes may occur under abusive conditions, which would further lead to the thermal failure of LIBs. Besides, the thermal hazards generally manifest as the thermal runaway behaviors such as high-temperature, ejection, combustion, explosion and toxic gases for a single battery, and it can even evolve to thermal failure propagation within a battery pack. To decrease these hazards, some countermeasures are reviewed including the application of safety devices, fire-retardant additives, battery management systems, hazard warnings and firefighting should a hazard occur.

Ethanol is often used as a humectant during the storage of nitrocellulose (NC). To mitigate the fire hazard of NC, which is a highly flammable compound, during storage, and to understand the fire hazards of NC–ethanol mixtures, it is imperative to study the thermal behavior of NC–ethanol mixtures and determine the optimal range of ethanol content in the mixture. In this study, the decomposition and burning behaviors of NC–ethanol mixtures with different ethanol contents (0–100%) were studied via thermogravimetric (TG) analysis and cone calorimetry (ISO 5660), respectively. The results of TG/differential TG analyses suggested that NC samples with a low ethanol content are more prone to thermal runaway such as burning or explosion during their decomposition under a constant temperature increase. Furthermore, ignition and burning characteristics of the mixtures, which were analyzed by cone calorimetry, revealed that the ignition of the sample is mainly caused by the volatilization of ethanol. According to the results, an ethanol content of ~ 30–50% helps reduce the thermal hazard of NC during fire. This study provides a perspective on ensuring the safe storage of NC, and elucidates effective fire suppression and rescue measures for fires caused by such materials.Graphic abstract

Nitrated cellulose (NC) is highly susceptible to thermal runaway such as combustion or explosion during decomposition. Preventing and mitigating the related accidents require more comprehensive analysis of its thermal stability and chemical decomposition kinetics. To understand the effect of combustion on the decomposition mechanism of NC, it is necessary to compare the kinetics in stable decomposition and combustion. In this study, multiple kinetic analyses including model-free and master-plots approaches were used to determine the kinetic parameters and kinetic model of NC in these two cases. The average activation energy (E) was found to be lower in combustion than that in stable decomposition (89.5–97.5 vs. 123.3–145.8 kJ mol−1). The stable decomposition kinetics fits the sigmoidal model, while the combustion kinetics fits the deceleration model. From the compensation effect, the pre-exponential factor was calculated to be 19.0–67.2 ln s−1 for stable decomposition and 12.9–26.1 ln s−1 for combustion. This study provides a new perspective on the methods to determine the compensation effect and expands the research scenarios of thermochemical kinetics.

Understanding the thermal runaway mechanism of lithium-ion batteries under low pressure and low temperature is paramount for their application and transportation in the aviation industry. This work investigated the coupling effects of ambient pressure (100 kPa, 70 kPa, 40 kPa) and ambient temperature (−15 °C, 0 °C, 25 °C) on thermal behaviors in an altitude temperature chamber. The experimental results indicate that lowering ambient pressure and temperature could attenuate the thermal runaway intensity, which is mainly attributable to the reduction in oxygen concentration and the increase in heat loss. Such a dual effect leads to the maximum temperature decreasing from 811.9 °C to 667.5 °C, and the maximum temperature rate declines up to 2.6 times. Correspondingly, the whole thermal runaway process is deferred, the total time increases from 370 s to 503 s, and the time interval, Δt, from safety venting gains by 32.3% as the ambient pressure and temperature decrease. This work delivers an in-depth understanding of the thermal characteristics under low pressure and low temperature and provides meritorious guidance for the safety of cell transportation in aviation.

The associations between the weight gain rate and neonate intensive care unit (NICU) outcomes were analyzed using the non-parametric Spearman's correlation coefficient test (ρ). There were no significant differences in demographic data between the two groups [Table 1]. Descriptions Tracheotomy group (n = 14) Non-tracheotomy group* (n = 12) χ2/Z/t values P values Gestational age (weeks) 37.70 ± 3.80 38.99 ± 1.83 1.087 0.288 Birth weight (g) 2823.57 ± 948.89 3320.83 ± 378.76 1.699 0.102 Male 9 7 0.097 0.756 SGA 5 3 0.188 0.665 Onset within 24 h after birth 12 11 0.224 0.636 Corrected age on admission (weeks) 42.22 ± 5.03 40.95 ± 1.87 -1.129 0.270 Weight on admission (g) 3032.14 ± 569.50 3290.83 ± 429.22 1.289 0.210 Ventilation support 0.042 0.838 Intubated on SIMV 10 9 SIMV and then/or NCPAP 14 12 Diagnosis 7.564 0.109 Bilateral vocal cord paralysis 7 6 Vocal cord/subglottic mass 2 3 Laryngotracheomalacia 2 1 Anomaly/defect of throat/larynx 3 0 Unknown 0 2 Age on tracheotomy indications assessed (days) 15.00 (4.75, 25.75) 14.00 (4.00, 25.00) -0.384 0.701 Corrected age at discharge (weeks) 47.49 ± 4.98 43.21 ± 2.62 -2.414 0.024 Discharge weight (g) 3502.14 ± 532.88 3535.83 ± 468.49 0.282 0.780 Death in hospital 1 0 0.891 0.345 DAMA 2 8 5.441 0.020 Total NICU stay (days) 37.0 ± 12.2 15.9 ± 7.4 5.229 <0.001 Total follow-up rate (%) 88.9 30.0 24.116 <0.001 Proportion of follow-up At 3 months 13/13 5/12 7.838 <0.001 At 6 months 10/12 2/10 6.455 0.011 At 12 months 9/11 2/8 4.024 0.045 Data are shown as mean±standard deviation, median (P25, P75), or n (%).*Patients in this group met the indications of tracheotomy but parents did not sign the consent for operation.DAMA: Owing to the high rate of patients lost to follow-up, no data regarding the post-discharge mortality could be obtained for the non-tracheotomy group.

Thermal failure propagation is one of the most severe challenges for battery modules and it usually aggravates the thermal hazards, further resulting in serious accidents. This work conducted two groups of experiments to investigate the influence of discharging treatment and module shape on the thermal failure propagation of battery modules, where the triangle module, rectangle module, parallelogram module, line module, hexagon module, and square module were researched. Based on the results, it can be found that an evident domino effect existed on the thermal failure propagation of battery modules. Namely, the failure propagation process consisted of several phases and the number of phases depended on the shape of the module. Besides, it is indicated that discharging treatment on a battery module when it was in a high-temperature environment would aggravate its thermal failure propagation by bringing an earlier thermal failure, a quicker failure propagation, and a larger mass loss. Combining the results of safety and space utilization, it is revealed that the triangular module may be the best choice of battery module due to its smaller failure propagation speed and higher space utilization.

Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, and the construction of a temperature–composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 μm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells.

Temperature is an important factor affecting the working efficiency and service life of lithium-ion battery (LIB). This study carried out the experiments on the thermal performances of Sanyo ternary and Sony LiFePO4 batteries under different working conditions including extreme conditions, natural convection cooling and phase change material (PCM) cooling. The results showed that PCM could absorb some heat during the charging and discharging process, effectively reduce the temperature and keep the capacity stable. The average highest temperature of Sanyo LIB under PCM cooling was about 54.4 °C and decreased about 12.3 °C compared with natural convection in the 2 C charging and discharging cycles. It was found that the addition of heat dissipation fins could reduce the surface temperature, but the effect was not obvious. In addition, the charge and discharge cycles of the two kinds of LIBs were compared at the discharge rates of 1 C and 2 C. Compared with natural convection cooling, the highest temperature of Sanyo LIB with PCM cooling decreased about 4.7 °C and 12.8 °C for 1 C and 2 C discharging respectively, and the temperature of Sony LIB highest decreased about 1.1 °C and 2 °C.

With the increasing demand for energy capacity and power density in battery systems, the thermal safety of lithium-ion batteries has become a major challenge for the upcoming decade. The heat transfer during the battery thermal runaway provides insight into thermal propagation. A better understanding of the heat exchange process improves a safer design and enhances battery thermal management performance. This work proposes a three-dimensional thermal model for the battery pack simulation by applying an in-house model to study the internal battery thermal propagation effect under the computational fluid dynamics (CFD) simulation framework. The simulation results were validated with the experimental data. The detailed temperature distribution and heat transfer behaviour were simulated and analyzed. The thermal behaviour and cooling performance were compared by changing the abnormal heat generation locations inside the battery pack. The results indicated that various abnormal heat locations disperse heat to the surrounding coolant and other cells. According to the current battery pack setups, the maximum temperature of Row 2 cases can be increased by 2.93%, and the temperature difference was also increased. Overall, a new analytical approach has been demonstrated to investigate several stipulating battery thermal propagation scenarios for enhancing battery thermal performances.