Search Results (914)

The Dengying Formation gas reservoir in the Penglai gas field, located in the central Sichuan Basin, exhibits substantial resource potential and promising development prospects. This reservoir is characterized by well-developed fractures and dissolution cavities, strong heterogeneity, complex gas–water relationships, and widespread edge–bottom water. During production, edge–bottom water is prone to channeling and intrusion through high-permeability pathways, which severely constrains well productivity and overall gas recovery. To address these challenges, this study takes a fractured-vuggy carbonate edge–bottom water gas reservoir as an example. By integrating large-scale physical simulation with cross-scale numerical simulation, a rational production allocation method suitable for strongly heterogeneous gas reservoirs has been developed. The research results indicate that: (1) Large-scale physical simulation experiments demonstrate that for fractured-vuggy bottom water gas reservoirs, implementing rate reduction and pressure control after water breakthrough can effectively suppress water invasion and coning, extend the stable production period, and increase the recovery factor by approximately 16%; (2) Based on the dynamic characteristics of water invasion, key similarity criteria including the Bond number, capillary number, gravity–viscous force ratio, and geometric–temporal similarity ratio were selected to establish a scientific parameter design method for cross-scale numerical simulation; (3) By considering factors such as reservoir type and aquifer energy, single-well mechanistic models were used to determine appropriate production rates for individual wells, enabling rapid optimization of production allocation plans. This provides crucial guidance for efficient gas well development and surface facility planning. Full article

The aim of this work was to explore and test the concept of a novel direct nucleation control method with external dissolution of fine crystals (E-DNC). It was postulated that the heating cycles of the internal DNC method could be transferred from the crystallizer jacket to an electrically heated recirculation tube, thereby using less energy and requiring a shorter time compared to internal DNC. The conceptual model was explored and developed by reviewing previous research on the topic and addressing known drawbacks. Engineering experience and a heuristic approach led to the conclusion that five commonly used controllers would suffice for a straightforward implementation of the method. A simplified simulation was developed to compare the time and energy requirements for the internal and external DNC methods, and it was concluded that external DNC uses 37% less energy and 19% less time compared to internal DNC. The laboratory system was then constructed by modifying the internal DNC apparatus with inexpensive and commonly used components. A linear cooling experiment was performed to establish the baseline for comparison with E-DNC experiments and to set the expected count range. The E-DNC experiments were then conducted with the aim of obtaining larger crystal sizes, and it was shown that the process could be designed in only three experiments. Adjusting the heating rate and count limit led to a significant increase in median crystal size (22.5%) compared to linear cooling. Full article

The Beishan area of Gansu, China, is the primary candidate site for the geological disposal of China’s high-level radioactive waste (HLW). To assess the long-term safety of this repository, the evolutionary patterns of groundwater and the primary migration vector of radionuclides must be understood. Through experiments and hydrogeochemical simulations of snowmelt samples from the Qilian Mountains and deep rock samples from Beishan, we reveal different hydrochemical compositions and types of the snowmelt and deep groundwater. The results show that the hydrochemical type of Qilian Mountain snowmelt is SO₄–Na·Ca, whereas that of the deep groundwater in the Beishan is Cl·SO₄–Na, indicating substantial differences in the hydrochemical characteristics of the two samples. The water–rock interactions between snowmelt and granite are dominated by the dissolution of silicate minerals and the precipitation of carbonate minerals, accompanied by cation exchange and adsorption. After the interaction, the hydrochemical type of the snowmelt becomes SO₄–Na, with total dissolved solids (TDS) consistently maintained at ~500 mg/L, which is distinct from the TDS range of 1540–2045 mg/L observed for the deep groundwater in the Beishan. Under the experimental and simulation conditions set in this study, the water–rock interactions between Qilian Mountain snowmelt and Beishan granite cannot reproduce the hydrochemical characteristics of the deep groundwater in the Beishan. This study provides theoretical support for the hydrogeological safety assessment of HLW geological repositories. Full article

Copper (Cu) smelting slags are considered secondary reserves of technology metals (TMs) and base metals (BMs), which are crucial for the transition to renewable energy and mechatronic applications. In this study, thermochemical and experimental analyses were conducted to investigate the pyrometallurgical extraction of TMs and BMs from Cu smelting slag. FactSage thermochemical simulations and smelting experiments were carried out at temperatures from 1300 to 1600 °C and with carbon (reductant) additions of 2% to 10% relative to the mass of the feed slag. The results showed that during smelting, gallium (Ga), germanium (Ge), cobalt (Co), and copper (Cu) deported into the iron-based alloy product. Zinc (Zn) and lead (Pb) oxidised to ZnO and PbO, respectively, which were subsequently collected as fumes. The produced alloy mass was more sensitive to carbon addition than to smelting temperature variation. The TM and BM contents in the alloy decreased with increasing carbon addition in the feed; this was attributed to dilution by Fe, Si, and C from the increasing reduction of iron and silicon oxides in the feed slag and dissolution of C in the alloy. High recovery degrees of TMs and BMs in the alloy stream—over 90% for Co and Cu, over 50% for Ga, and over 70% for Ge—were achieved when smelting at 1500 °C with 4% carbon addition. The final alloy comprised 70.5% Fe, 6.6% Co, 23.6% Cu, 0.11% Ga, and 0.13% Ge. The fumes primarily comprised ZnO and, to a lesser extent, PbO, with recovery degrees over 90% for Zn and Pb. These alloy and fume products would be processed following conventional hydrometallurgical separation and purification processes to produce high-purity metals. The pyrometallurgical extraction of TMs and BMs presents an opportunity for the valorisation of Cu smelting slag dumps, especially in Southern Africa, aiming to attain zero-waste industrial processes. Full article

Background: This study aimed to investigate, from a scientific and formulation perspective, an oral semaglutide tablet incorporating sodium caprate (C10) as an intestinal absorption enhancer and to optimize its formulation performance using a Quality by Design (QbD)-based approach. Semaglutide—a peptide-based therapeutic—provides effective glycemic control and weight reduction; however, its extremely low oral bioavailability has limited administration to subcutaneous injection. Although various attempts have been made to improve peptide absorption, achieving consistent delivery through oral routes remains a significant challenge due to enzymatic degradation and poor membrane permeability. Methods: To overcome these limitations, an absorption enhancer (sodium caprate) was incorporated to enhance oral absorption, and a Quality by Design (QbD)-based approach was applied to systematically guide formulation development. Following the definition of the Quality Target Product Profile and critical quality attributes, risk assessments (Preliminary Hazard Analysis and Failure Mode and Effects Analysis) were conducted to identify key formulation factors. A design of experiments approach was then employed to determine the optimal tablet composition. Results: Consequently, the resulting formulation met all predefined quality criteria, including hardness, disintegration, friability, and content uniformity. In addition, the in vitro dissolution profile demonstrated a release pattern comparable to that of the reference product, with similarity factor values of 74.4, 74.7, and 71.3 at pH 1.2, 4.0, and 6.8, respectively. Conclusions: These findings indicate that the formulation can achieve consistent and reproducible quality performance as an oral semaglutide dosage form. The QbD-based formulation design strategy presented in this study provides a robust and broadly applicable approach for developing oral delivery systems for peptide drugs, including semaglutide, and ultimately provides useful formulation insight for future peptide-based oral delivery research. Full article

Background/Objectives: Amorphous solid dispersions (ASDs) produced via hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing represent a promising strategy for improving the performance of poorly water-soluble drugs. However, the integrated HME-FDM workflow is inherently energy-intensive, and sustainability considerations are rarely incorporated into formulation and process optimization. The present study aimed to develop and optimize indomethacin (IND) ASDs using a systematic Design of Experiment (DoE) framework that integrates electrical energy consumption as a quantitative response alongside pharmaceutical performance attributes. Methods: Polymer–plasticizer miscibility was screened using hot-stage microscopy, followed by filament preparation via HME. A factorial DoE was applied to optimize drug loading and extrusion temperature considering electrical energy consumption, extrusion yield, encapsulation efficiency, and residual crystallinity. Solid-state characterization was performed using DSC and XRD. The optimized filament was subsequently subjected to geometry screening and a second DoE to optimize platform temperature, nozzle temperature, and printing speed with respect to printing time, electrical energy consumption, and drug assay. Results: Complete drug amorphization was achieved within a defined thermal window, with residual crystallinity governed by kinetic dissolution constraints at lower extrusion temperatures. Electrical energy demand during both HME and FDM was strongly influenced by thermal setpoints and process duration. Multi-response overlay analysis identified sustainability-oriented operating windows for both stages. Experimental validation confirmed close agreement between predicted and observed responses, demonstrating simultaneous reduction in electrical demand and maintenance of dose accuracy and solid-state stability. Conclusions: This study demonstrates that electrical energy consumption can be systematically embedded as a quantitative design variable in pharmaceutical process optimization. The proposed dual-stage DoE strategy establishes a rational framework for developing 3D-printed ASD dosage forms that balance molecular performance and environmental efficiency. Full article

Electrokinetic remediation (EKR) was evaluated in naturally contaminated vineyard soils to assess copper redistribution, treatment redistribution efficiency, and changes in copper fractions across contrasting soil pH conditions. Ten vineyard soils (five acidic, five alkaline) were subjected to a 30-day ex situ EKR experiment under a constant electric field. Total copper content was measured in the anode, cathode, and inter-electrode zones, while copper fractions were quantified only in electrode zones exhibiting the most pronounced post-remediation decrease in total copper. The findings demonstrate that the EKR process generated distinct, soil-type-dependent gradients in copper mobility. In acidic soils, copper exhibited pronounced central-zone accumulation with notable depletion toward the anode, whereas in alkaline soils, the lowest concentrations consistently occurred near the cathode and increased toward the anode. Notably, one slightly alkaline soil displayed the highest redistribution efficiency (43.0%), underscoring the strong influence of soil chemistry on EKR performance. Redistribution efficiencies averaged 29.5% in acidic soils and 12.8% in alkaline soils, although localized acidification enabled notably higher redistribution in highly contaminated samples. These trends reflected on copper fractions: acidic soils showed enhanced release from Fe/Mn oxides and carbonates, while alkaline soils experienced stronger short-term mobilization driven by cation competition and dissolution of less stable oxide phases. Fractionation results indicated that the Fe/Mn oxide-bound fraction was the most susceptible to electromigration, while both acidic and alkaline soils ultimately shifted copper toward less extractable operational fractions. Full article

To investigate the deterioration law of the mechanical properties of PVA-fiber-reinforced rubber concrete under the combined action of high-temperature and salt erosion, physical index tests, dynamic mechanical property experiments, and microstructural morphology observations were carried out on specimens subjected to different temperatures (ambient temperature, 100 °C, 300 °C) and various solution attacks (water, 5% NaCl, 5% Na₂SO₄, and 5% NaCl + 5% Na₂SO₄ mixture). The results show that, after exposure to 300 °C, the PVA fibers melt and the rubber pyrolyzes, since this temperature exceeds their melting points. A residual pore network is formed inside the matrix, and the damage degree of ultrasonic pulse velocity is about 2.3 times that of the 100 °C group. Although salt solution and its crystallization products can physically fill the pores and cause a partial recovery of pulse velocity, this change is mainly due to the alteration of the pore medium and does not represent a substantial restoration of the microstructure. The effects of different salt solutions on dynamic mechanical properties vary significantly: Sulfate erosion improves the dynamic performance significantly at ambient temperature by forming gypsum and ettringite to fill pores, but this strengthening effect disappears after 300 °C. Sodium chloride attack generates Friedel’s salt and consumes C₃A, leading to general strength deterioration. In composite salt erosion, the competitive and synergistic effects of Cl⁻ and SO₄²⁻ destabilize erosion products and weaken interfacial bonding, resulting in consistent decreases in dynamic compressive strength and elastic modulus under all temperatures and impact pressures. The strength reduction reaches 66.2% after 300 °C. Microscopic analysis confirms that composite salt erosion leads to the dissolution of ettringite and loose structure, which verifies the synergistic deterioration law of macroscopic properties. This study systematically reveals the damage evolution mechanism of PVA-fiber-reinforced rubber concrete under the coupled action of high-temperature and salt erosion, and provides a theoretical basis for the dynamic bearing capacity evaluation and durability design of concrete structures in such coupled environments. Full article

Background/Objectives: Biorelevant in vitro dissolution testing is used increasingly to predict complex mechanisms in the gastrointestinal (GI) tract that determine oral bioavailability. However, the limited use of non-compendial systems is driven by the lack of widely accepted, standardized validation frameworks. This ongoing gap continues to restrict their adoption relative to United States Pharmacopeia (USP) apparatus. While the physiological relevance and biopredictive capabilities of the tiny-TIM and TIM-1 in vitro GI models have been demonstrated in previous studies, their inter-laboratory reproducibility has not been systematically established. Therefore, this international ring study evaluates the reproducibility of in vitro simulations of GI transit and absorption of paracetamol in fasted- and fed-state conditions in tiny-TIM and TIM-1. Methods: Three laboratories used TIM-1 and five used tiny-TIM to simulate oral administration of a 500 mg paracetamol solution to a healthy adult. Paracetamol solution was selected as a well-characterized and widely available BCS I compound to minimize formulation and solubility effects and focus on system performance, enabling the generation of a generic validation dataset for the reproducibility of TIM experiments. Results: Paracetamol bioaccessibility profiles were repeatable and reproducible (all pairwise f₂ > 50). Maximum differences in total bioaccessible paracetamol were 0.9% (TIM-1) and 2.8% (tiny-TIM) within laboratories and 3.4 and 5.9% between laboratories. Inter-lab variability at individual time points remained <4.0% (fasted) and 5.2% (fed). Both TIM models produced biopredictive metrics, correctly predicting no food effect on total paracetamol bioaccessibility and capturing delayed t_max. Gastric and intestinal environments showed repeatable pH, temperature, and GI transit characteristics, with fluctuations across transit stages that mirrored reported in vivo patterns. Conclusions: These results demonstrate that TIM systems can reproducibly simulate gastrointestinal conditions across laboratories and generate consistent measurements of drug product performance, despite the complexity of the dynamic processes involved. While this evaluation involving a single BCS I drug solution should not be directly extrapolated to experiments with poorly soluble compounds or different formulations, it supports the use of TIM systems as robust in vitro models in drug product development. This study provides a standardized, inter-laboratory, baseline performance dataset to support regulatory submissions incorporating TIM data and enable more confident interpretation of TIM experiments. Full article

The mineralogical composition, textural characteristics, and uranium occurrence of sandstone-hosted uranium ores significantly influence the leaching performance during in situ recovery. This study investigates ore samples from the Zhenyuan uranium deposit, China, utilizing SEM, EPMA, XRD, and XRF to characterize their texture and mineralogy. Combined with thin-section leaching tests, batch stirring experiments, and pressurized column leaching experiments, the leaching behavior of pitchblende, associated gangue minerals, and the whole rocks were evaluated. The results indicate that: Uranium mainly occurs as nano-spherical and film-like pitchblende distributed along the edges of detrital grains and Ti-oxides. Minor uranium is incorporated into Ti-oxides and dolomite lattices via isomorphic substitution or adsorbed by chlorite. Under CO₂ + O₂ leaching conditions, pitchblende was almost completely dissolved, while U-bearing Ti-oxides experienced slight corrosion. Dolomite underwent partial dissolution, providing bicarbonate ions and improving rock permeability. Pyrite dissolution was limited during the early stage of leaching. The high dolomite content, low clay abundance, favorable pore structure, and easily leachable pitchblende suggest that the Zhenyuan deposit is well suited for CO₂ + O₂ in situ recovery. Increasing CO₂ pressure is recommended to enhance dolomite dissolution and improve uranium recovery efficiency. Full article

The long-term accumulation of phosphogypsum (PG) stacks has caused combined pollution of total phosphorus (TP), fluoride (F⁻), metals and metalloids (MMs), posing a severe threat to regional ecological security. To clarify the migration characteristics of pollutants in PG stacks, water leaching experiments and environmental risk assessment were conducted in 21 typical PG stacks in Southwest China. The spatial differentiation and vertical migration characteristics of pollutants under various coverage measures (high-density polyethylene (HDPE) film covering, soil covering, a composite of film–soil covering, and open-air storage) at different pH conditions were systematically analyzed. Results indicated that under open-air stockpiling conditions, the surface accumulation of TP and F⁻ was the most significant among all covering measures, corresponding to the highest environmental risk. In contrast, the membrane–soil composite covering exhibited the optimal inhibitory effect on the surface diffusion of TP and F⁻, but was less effective for metal and metalloid enrichment. Under acidic conditions (pH < 6), the vertical migration capacity of TP, F⁻, and MMs (Cu, Cd, Cr, Pb, and Zn) increased, leading to enrichment in the deep layers of the stack. With the increase in pH, the calcium-mediated precipitation–adsorption effect created a “geochemical barrier”, facilitating the solid-phase fixation of pollutants. A significant positive correlation among pollutants indicates synergistic release and fixation behaviors. In addition, a pH-controlled P-F-MM source-to-sink conceptual model was established, outlining the dissolution, precipitation, adsorption, fixation and re-enrichment pathway from fresh stock to leachate. This work provides insights for optimizing cover designs and pollution control strategies. Full article

Objective: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong–Vinegar cyperus rotundus based on Quality by Design (QbD) principles. Methods: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS). Single-factor experiments were conducted to preselect the inclusion speed based on ligustilide and α-cyperone content as evaluation criteria. Subsequently, using the inclusion rates of ligustilide and α-cyperone as evaluation criteria, a factorial design was employed to investigate the inclusion temperature, inclusion time, and the volume ratio of β-cyclodextrin solution to essential oil, thereby optimizing the inclusion process parameters. Finally, the inclusion process parameters were validated, and the inclusion rates were determined. The obtained inclusion complexes were characterized by microscopic analysis, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Furthermore, phase dissolution studies and molecular docking were employed for confirmation. Results: The optimal process parameters were determined as follows: encapsulation speed of 300 rpm, β-cyclodextrin solution excess of 6, encapsulation time of 2.5~3 h, and encapsulation temperature of 30~35 °C. The encapsulation rates for ligustilide and α-cyperone in the resulting inclusion complex were 63.15~64.74% and 71.33~76.89%, respectively. Structural characterization confirmed the formation of the inclusion complex. Conclusions: This inclusion process is reliable and provides a reference for preparing β-cyclodextrin inclusion complexes of volatile oils in formulations containing the Chuanxiong–Vinegar cyperus rotundus drug pair. Full article

This study aimed to develop a 100 mg immediate-release (IR) tablet containing dasatinib monohydrate, a tyrosine kinase inhibitor, using a Quality by Design (QbD) framework at laboratory scale. The development strategy focused on systematic identification and control of critical process parameters (CPPs) affecting tablet quality during wet granulation. Preformulation studies were conducted to evaluate key physicochemical properties of the active pharmaceutical ingredient (API), including solubility, particle size distribution, and crystallinity, which may influence dissolution behavior. A risk assessment approach based on preliminary hazard analysis (PHA) and failure mode and effects analysis (FMEA) was applied to identify high-risk process variables. Based on the risk assessment results, chopper speed during wet granulation and compression force during tableting were identified as critical process parameters. These factors were further investigated using a Design of Experiments (DoE) approach based on Define Custom Design (DCD) and response surface methodology (RSM) to evaluate their effects on critical quality attributes (CQAs), including dissolution performance, disintegration time, and tablet friability. Response surface analysis established a design space in which chopper speed ranged from approximately 2300–2500 rpm and compression force ranged from 11 to 13 kN, ensuring consistent tablet quality within the investigated operating range. The optimized process conditions produced tablets that satisfied predefined quality targets. Comparative dissolution studies demonstrated dissolution profiles comparable to the reference product across pH 1.2, 4.0, and 6.8 media, with similarity factor (f₂) values ranging from 51.18 to 85.23. The experimentally established design space demonstrated reproducible in vitro performance and physicochemical stability under accelerated storage conditions. Overall, this study demonstrates the practical application of a QbD-based development strategy integrating risk assessment and response surface optimization to improve process understanding and manufacturing robustness in wet granulation-based tablet production. Full article

The development of collagen-based composite materials offers new opportunities for designing bioactive porous structures with tunable properties. This study focuses on sponges or scaffolds fabricated from fish skin-derived tropocollagen combined with detonation nanodiamonds (NDs), aiming to explore how incorporation of NDs and application of radiation, as a potential sterilization method, influence structural and functional characteristics of the material. Freeze-dry methods of sponge fabrication resulted in a bilayered structure of open porosity, with microporosity at the top and a microchannel at the lower part of the material. The sponges demonstrated mechanical properties with relatively low elongation of below 10%, while the maximum stress was reduced by ca. 20% due to irradiation. Hydration and absorption experiments, mimicking the resorption of collagen in physiological conditions of expected application as wound dressing material, demonstrated controllable fluid uptake and gradual material dissolution, taking place over several hours, depending essentially on the irradiation treatment and morphological characteristics of the sponge. These findings highlight the versatility of collagen–nanodiamond composites as platforms, in which structural design and processing parameters control performance. Moreover, they provide a strong indication of the expected behavior of collagen–nanoparticle systems, including those incorporating NDs modified to impart specific biological functionality, such as antimicrobial activity. Full article

The performance of flux-cored Zn-Al filler metal is susceptible to corrosion-induced degradation, thereby impairing its brazability. In this study, flux-cored Zn-2Al filler metals are prepared, and the salt spray test is subsequently carried out on the prepared filler metals. Scanning transmission electron microscope is used to identify the phases in filler metals. An electrochemical workstation was employed to test the electrochemical performance of the filler metals. The corrosion pathways and evolution patterns of filler metals are analyzed. The findings demonstrate that the corrosion type of the filler metals is electrochemical corrosion, characterized primarily by the corrosion modes of pitting corrosion and intergranular corrosion. The cathode is the α-Al phase, which undergoes an oxygen-absorption corrosion reaction, while the anode is the η-Zn phase, which experiences corrosion and subsequent dissolution. The continuously distributed α-Al phase bands and discontinuously distributed large-sized rod-like α-Al phases accelerate the corrosion rate, and the corrosion propagation rate along the extrusion direction is higher than that in the radially inward direction. After 15 days of salt spray corrosion, the tensile strength of filler metals decreases by 16.2%, and the elongation rate decreases to 3.73%. Full article