Stability Studies Research Articles

Heteroleptic Triazole-Bisoxazoline Iron Complexes Reveal Lability of the Iron-Carbene Bond Even Within a Chelating Scaffold.

N-Heterocyclic carbenes have proven to be excellent ligands for transition metals, with numerous applications in catalysis and beyond. However, they have also displayed lability with first row transition metals, largely due to the hard-soft mismatch of the metal-carbon bond. Chelation is often considered a suitable methodology for supporting the labile M-C bond through the introduction of a strongly coordinating donor site such as hard phenolates. Herein, we demonstrate that chelating phenolate-carbene ligands are kinetically labile in iron(II) complexes. Specifically, heteroleptic iron complexes [Fe(C^O)(N^N)] were synthesized composed of a phenolate-functionalized triazolylidene (CO) ligand and N,N-bidentate coordinating bisoxazoline ligand (N^N). Stability studies by 1H NMR spectroscopy showed that the heteroleptic complexes preferentially convert to their corresponding homoleptic complexes [Fe(C^O)2] and [Fe(N^N)2], indicating reversible decoordination of the carbene phenolate chelate from the iron center. The rate of this rearrangement is dependent on the substituents on the ligands and increases for triazolylidene wingtip groups mesityl (Mes) < di(isopropyl)aryl (DIPP) < adamantyl (Ad), with significant ligand redistribution for DIPP and Ad systems observed even at room temperature. The most stable heteroleptic complex featured mesityl wingtips on the triazole and phenyl groups as oxazoline substituents and displayed signs of ligand exchange only after 16 h at room temperature. This substitutional lability of carbene ligands even when supported by a phenolate chelating group has direct consequences when designing iron complexes for catalytic applications.

Assessment of Quality Control parameters under Accelerated Stability Conditions for Manasamitra Vatakam; A Herbo Mineral Formulation

Accelerated Stability Studies predicts the stability data and significantly explains the drug decision process. In the present study, Manasamitra Vatakam, a Herbo mineral formulation was subjected to stability conditions at 40°C ± 2°C /75%± 5% RH for 06 months. Control and stability samples were determined for parameters like Weight variation, Moisture content, Marker content determination, and Disintegration test, Dissolution study with different mediums, Friability and Hardness test. The phytomarker analysis showed decrease assay value for β-sitosterol, Vitexin, Kampferol and Withaferin. The dissolution studies were performed for the major biomarker Berberine in 0.1N HCl, pH 4.5 acetate and pH 6.8 phosphate buffer in which pH 6.8 buffer showed maximum release of 66.82% at 04 hours. The other Quality control parameters showed minimal difference under acceptance criteria. The study explains the need of stability analysis in polyherbal formulations and developed method can be used for routine analytical studies in various formulation containing berberine. Keywords: Berberine, HPLC, Manasamitra Vatakam, Quality Control, Stability.

Novel antimicrobial peptides based on Protegrin-1: In silico and in vitro assessments

The development of antibiotic resistance has caused significant health problems. Antimicrobial peptides (AMPs) are considered next-generation antibiotics. Protegrin-1 (PG-1) is a β-hairpin AMP with a membrane-binding capacity. This study used twelve PG-1 analogs with different amino acid substitutions. Coarse-grained molecular dynamics (MD) simulations were used to assess these analogs, and their physicochemical properties were computed using the Antimicrobial Peptide Database. Three AMPs, PEP-D, PEP-C, and PEP-H, were chosen and synthesized for antibacterial testing. The microbroth dilution technique and hemolytic assays evaluated the antimicrobial efficacy and cellular toxicity. The checkerboard method was used to test the combined activity of AMP and standard antibiotics. Cell membrane permeability and electron microscopy were used to evaluate the mode of action. The chemical stability of the selective AMP, PEP-D, was assessed by a validated HPLC method. PEP-D consists of 16–18 amino acid residues and has a charge of +7 and a hydrophobicity of 44 %, similar to PG-1. It can efficiently inactivate bacteria by disrupting cell membranes and significantly reducing hemolytic activity. Chemical stability studies indicated that AMP was stable at 40 °C for six months under autoclave conditions. This study could introduce the potential therapeutic application of selective AMP as an anti-infective agent.

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0–24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

An amperometric stability study of titanium dioxide nanoparticle layer on interdigitated electrode contact based on morphology, structure, and surface-induced response

This paper investigates the amperometric stability of a Titanium Dioxide (TiO2) nanoparticle layer on an interdigitated electrode (IDE) to develop stable electronic devices. The devices were tested with varying numbers of spin-coat layers and annealing temperatures to achieve a TiO2 nanoparticle layer with high crystallinity. Device fabrication involved coating a TiO2 solution onto a silicon dioxide (SiO2) wafer with an IDE photomask. The devices were characterized using a Field-emission Scanning Electron Microscope (FESEM) and X-ray Diffractometer (XRD) to verify the crystallinity of the TiO2. Current-voltage (I-V) curves and real-time current measurements were also conducted to analyze the electrical properties of the device. FESEM results indicate that increasing the number of spin-coat layers and annealing temperature enhances the clarity of the spherical shape of TiO2 nanoparticles and produces highly crystalline nanoparticles, as confirmed by XRD analysis. In terms of electrical analysis, the device exhibited a sharp increase in current, maintaining a range of 2.5 nA to 10 nA. This concludes that the TiO2 device is highly sensitive, with excellent repeatability and response time, making it suitable for practical applications.

Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging.

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (99mTc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99mTc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh2), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99mTc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97-98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD7.4 values (1.6-2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac-[99mTc(CO)3(Cip-DTC)(PPh3)] (2') showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac-[99mTc(CO)3(Cip-DTC)(TMPP)] (3') demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99mTc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals.

Unveiling Niaprazine's Potential: Behavioral Insights into a Re-Emerging Anxiolytic Agent.

Ongoing global research actions seek to comprehensively understand the adverse impact of stress and anxiety on the physical and mental health of both human beings and animals. Niaprazine (NIA) is a chemical compound that belongs to the class of piperazine derivatives. This compound has recently gained renewed attention due to its potential therapeutic properties for treating certain conditions such as anxiety. Despite its potential benefits, the behavioral effects of NIA have not been thoroughly investigated. This study aimed to examine NIA's potential as an anti-anxiety and anti-stress agent. After administering either vehicle or NIA in their drinking water to mice for 14 days, we conducted behavioral analyses using the Marble Burying Test and the Elevated Plus Maze test. NIA-treated mice spend more time in the open arms and bury fewer marbles. Moreover, a stability study confirmed the linear relationship between NIA concentration and its response across concentrations encompassing the NIA mother solution and the NIA solutions administered to mice. Also, a preliminary synaptic toxicity analysis showed no direct damage to cortical nerve endings. Here, we show that NIA can modulate anxiety-related behaviors without significantly impacting exploratory activity or adverse effects. Our work describes new findings that contribute to the research on safer and more tolerable anxiety management options.

Two-positron-bonded dihalides: Ps2XY (X,Y=F,Cl,Br).

This study explores the energetic stability and physical prop-This study explores the energetic stability and physical properties of Ps2XY complexes formed by two halide anions (X-,Y-=F-,X-,Br-), and two positrons (Ps:positron-electronpair). We combine electronic coupled cluster (CCSD(T)) calculations with positronic multicomponent renormalized partialthird-order propagator (MC-REN-PP3) calculations to effectively recover correlation energies. Analysis of potential energy curves confirms the energetic stability of these positronicmolecules, with optimized structures identified as global minima. Further investigation of electron and positron densitiesreveals stabilization owing to the formation of two-positron bonds. The global stability of the Ps2XY complexes contrastswith the metastable two-positron-bonded (PsH)2, which energetically favors the emission of Ps2. Comparative analysis of one- and two-positron dihalides indicates that addinga positron to PsXY- generally results in shorter bond distances, higher force constants, and lower dissociation energies, with exceptions due to differences in positron affinities ofPsXY- and Y-. We explore the analogy between two-positron-bonded dihalide systems Ps2XY and two-electron-bonded dialkali molecules AB, (A,B=Na,K,Rb). The bonding properties in positron dihalides and their electronic dialkali analogs displayidentical periodic trends. However,compared to their isoelectronic AB counterparts, the positron bonds in Ps2XYhave shorter bond lengths, higher force constants, and higher bond energies.

R-C-D-F machine learning method to measure for geological structures in 3D point cloud of rock tunnel face

This study introduces an innovative Roughness-CANUPO-Dip-Facet (R-C-D-F) methodology for the measurement of dip angle and direction in geological rock facets. The R-C-D-F method is distinguished by its comprehensive four-step approach, encompassing filtration through roughness analysis, CANUPO analysis, and dip angle filtration, followed by facet segmentation as the measurement step. To achieve precise and efficient results, the method specifically focuses on isolating joint embedment, achieved by systematically filtering out joint bands. This selective filtration process ensures that measurements are conducted exclusively on relevant joint embedment points. The novelty of this methodology lies in its capability to automatically eliminate joint bands while retaining the joint embedment points, facilitating precise measurements without manual intervention. Three site models were evaluated using the R-C-D-F method, alongside four different techniques for measuring dip angle and direction: plane fitting, normal vector conversion, facet segmentation, and compass measurements. The results demonstrated that all methods accurately calculated the dip angle, with an accuracy ranging from 97 % to 99.4 %. The facet segmentation method was selected as the optimal measurement tool due to its automatic nature and capacity to provide accurate results without manual intervention. Furthermore, the optimal local neighbour radius (LNR) for calculating normal vectors was determined, with findings indicating that a larger LNR value enhances accuracy but also increases computational time. A verification was conducted to estimate the dip angle used for filtering and discarding additional points representing joint rock bands, with the optimal value being 45, 30, and 45 degrees for the respective sites.The R-C-D-F method effectively detected and eliminated 100 % of joint band points while retaining 81 % of joint embedment points, and the facet segmentation method provided accurate dip angle and direction measurements for each joint embedment segment. These outcomes underscore the robustness and precision of the R-C-D-F method in geological engineering and rock stability studies.

Design and fabrication of MnCo2O4@MnCo2S4 Core@Shell nanostructured arrays decorated over the rGO sheets for high-performance asymmetric supercapacitor

In order to create reliable and effective energy storage systems, it is crucial to choose electrode materials that exhibit high stability and energy density. In this work, MnCo2S4@MnCo2O4 core@shell nanoneedle-like nanostructures (MCS@MCO/rGO) are synthesised over a rGO sheet using an innovative and easy hydrothermal technique. Electrolyte transport and sulphur incorporation during charge-discharge reactions are both made easier by the core@shell nanostructured arrays' large active surface area. With an appropriate pore size distribution centred at 13.4 nm and a high surface area of 125.4 m2g-1, the ternary electrodes composed of MCS@MCO and rGO have a rich mesoporous structure. A specific capacitance of 1346 Fg-1 at 1 Ag-1 demonstrates the exceptional performance of the MCS@MCO/rGO ternary electrode. The MCS@MCO/rGO ternary electrodes show a remarkable cyclic stability of 88.9 % capacity retention over 10,000 cycles, according to the cycling stability studies. With an impressive power density of 1010 Wkg-1 and remarkable cycling stability (95.5 % retention of the original capacitance after 10,000 cycles), the manufactured MCS@MCO/rGO//AC ACS displays an impressive energy density of 57.5 Whkg-1. The mesoporous structure is excellent for increasing the characteristics of supercapacitor electrodes, as these astounding results can demonstrate.

Storage and Transportation of Hythane: Thermodynamics, Kinetics, and Stability Studies Using the Gas Hydrates Process

Storage and Transportation of Hythane: Thermodynamics, Kinetics, and Stability Studies Using the Gas Hydrates Process

γ-Cyclodextrin-metal organic framework as a carrier for trans-N-p-coumaroyltyramine: A study of drug solubability, stability, and inhibitory activity against α-glucosidase.

γ-Cyclodextrin-based metal-organic frameworks (γ-CD-MOF) were successfully synthesized using the solvent diffusion method and applied as carriers for trans-N-p-coumaroyltyramine (N-p-t-CT, NCT) to study the solubability, stability, sustained release and inhibitory activity against α-glucosidase. The solubilization effect of γ-CD-MOF on N-p-t-CT was performed using impregnation (NCT@CD-MOF-1) and co-crystallization (NCT@CD-MOF-2) methods. X-ray diffraction, scanning electron microscope (SEM), fourier transform infrared spectrometer (FTIR), and N2 adsorption/desorption were used to characterize the MOFs before and after loading NCT. The results showed that NCT@CD-MOF-2 had a better solubability for N-p-t-CT, 145.03μg/mg of drug loading capacity could be achieved, and the solubility of NCT@CD-MOF-2 in water was 366 times higher than free N-p-t-CT. In addition, the stabilities of N-p-t-CT under temperature, UV light and pH conditions were greatly improved after encapsulation in γ-CD-MOF. Furthermore, NCT@CD-MOFs had a sustained release of N-p-t-CT over an extended period in vitro due to the primary encapsulation in pore structures. Notably, γ-CD-MOF loaded with N-p-t-CT showed superior inhibitory activity against α-glucosidase compared to free N-p-t-CT. Cytotoxicity studies demonstrated that NCT@CD-MOF-2 had low toxicity in vitro and perfect biocompatibility with HL-7702 cells, and γ-CD-MOF could reduce the toxicity of free N-p-t-CT at higher concentrations.

Ensuring Stability of Anode Catalysts in PEMWE: From Material Design to Practical Application.

Proton Exchange Membrane Water Electrolysis (PEMWE) has emerged as a clean and effective approach for the conversion and storage of renewable electricity, particularly due to its compatibility with fluctuating photovoltaic and wind power. However, the high cost and limited performance of iridium oxide catalysts (i.e. IrO2) used as anode catalyst in industrial PEM electrolyzers remain significant obstacles to widespread application. Although numerous low-cost and efficient alternative catalysts have been developed in laboratory research, comprehensive stability studies critical for industrial use are often overlooked. This leads to the failure of performance transfer from catalysts tested in liquid half-cell systems to those employed in PEM electrolyzers. This concept presents a thorough overview for the stability issues of anode catalysts in PEMWE, and discuss their degradation mechanisms in both liquid half-cell systems and PEM electrolyzers. We summarize comprehensive protocol for the assessment and characterization, analyze the effective strategies for stability optimization, and explore the opportunities for designing viable anode catalysts for PEM electrolyzers.

Consequences of slope instability and existing practices of mitigation in hydropower projects of Nepal

IntroductionNepal has witnessed several instances of slope instability associated with Hydroelectric Projects in the recent decades. Despite this, slope instability tends to receive less attention compared to other hazards.ObjectivesThe objective of this study is to investigate fourteen hydroelectric projects with the aim of identifying the types and causes of slope failures. Additionally, it seeks to offer a comprehensive understanding of slope stability conditions and challenges encountered during construction at project sites.MethodsTo accomplish this, the study employs Key Informant Interviews with Questionnaires to delve into the slope stability concerns within Nepal’s hydropower projects. The findings are then validated through an extensive review of pertinent literature. To conduct a thorough assessment of slope stability, the study relies on on-site observations, measurements, investigations, and both in-situ and laboratory tests.ResultsIt becomes evident that the careful selection of study sites, the application of geotechnical methods, and the establishment of regular monitoring are pivotal for ensuring favorable slope stability outcomes.ConclusionA majority of respondents concur that cutslope is the primary factor causing slope instability with 44.4% answering affirmatively. An independent t-test reveals there is no significant difference between the variables. Moreover, the correlation which is closed to 1 suggests that perception of respondents are interconnected and tend to vary in a synchronized manner. Participants in the study widely acknowledge numerical modeling methods as a means to overcome the limitations of slope stability studies.

Preparation and Stability Study of an Injectable Hydrogel for Artificial Intraocular Lenses.

Currently available intraocular lenses (IOLs) on the market often differ significantly in elastic modulus compared to the natural human lens, which impairs their ability to respond effectively to the tension of the ciliary muscles for focal adjustment after implantation. In this study, we synthesized a polyacrylamide-sodium acrylate hydrogel (PAH) through the cross-linking polymerization of acrylamide and sodium acrylate. This hydrogel possesses excellent biocompatibility and exhibits several favorable properties. Notably, the hydrogel demonstrates high transparency (94%) and a refractive index (1.41 ± 0.07) that closely matches that of the human lens (1.42). Additionally, it shows strong compressive strength (14.00 kPa), good extensibility (1400%), and an appropriate swelling ratio (50 ± 2.5%). Crucially, the tensile modulus of the hydrogel is 2.07 kPa, which closely aligns with the elastic modulus of the human lens (1.70-2.10 kPa), enabling continuous focal adjustment under the tension exerted by the ciliary muscles.

A selective, sensitive and fast LC-MS/MS method for cabotegravir quantification in rat plasma and pharmacokinetic investigations.

This study presents a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying cabotegravir (CAB) in rat plasma. A novel, sensitive, and rapid LC-MS/MS method has been developed and validated. Furthermore, protein precipitation technique allowed us to lowered the limit of quantification (LOQ) to nanogram levels, allowing detection of smaller CAB amounts in plasma samples. A review of scientific literature reveals that this method is superior than published methods in terms of runtime, sensitivity, wide linearity, and cost, using LC-MS/MS to quantify CAB in biological samples. CAB reached its maximum concentration (Cmax) of 78.401 μg/mL in rat plasma at 1.50 h (Tmax). Linearity was evaluated across 0.05-1000 μg/mL for CAB using five calibration curves with at least nine standards each with r2 > 0.9997. The intra- and inter-day precision and accuracy results were below 15% and acceptable as per Food and Drug Administration (FDA) guidelines. Stability of compounds were established in a battery of stability studies, that is, benchtop, autosampler, and long-term storage stability as well as freeze thaw cycles. The validated method can be used as a routine method to support pharmacokinetic studies.

Discovery and structure − activity relationships of 2,4,5-trimethoxyphenyl pyrimidine derivatives as selective D5 receptor partial agonists

Dopamine receptors are therapeutic targets for the treatment of various neurological and psychiatric disorders, including Parkinson’s and Alzheimer’s. Previously, PF-06649751 (tavapadon), PF-2562 and PW0464 have been discovered as potent and selective G protein-biased D1/D5 receptor agonists with optimal pharmacokinetic properties. However, no selective D5R agonist has been reported yet. In this context, we designed and synthesized forty non-catecholamines-based pyrimidine derivatives and identified four pyrimidine derivatives as selective D5R partial agonists. Using cAMP-based GloSensor assay in transiently transfected HEK293T cells with human D1 or D5 receptors, we discovered that compound 5c (4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine) exhibited modest D5R agonist activity. This leads us to explore various modifications of this scaffold to improve the D5 agonist potency and efficacy. Using molecular docking, and rational design followed by their evaluation at D1 and D5 receptors for agonist activity, we identified three new derivatives, 5j, 5h, and 5e. The most potent compound of this series 5j (4-(4-iodophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine), exhibited EC50 of 269.7 ± 6.6 nM. Mice microsomal stability studies revealed that 5j is quite stable (>70 % at 1 hr). Furthermore, pharmacokinetic analysis of 5j (20 mg/kg, p.o) in C57BL/6j mice showed that 5j is readily absorbed via oral route of dosing and also enters into the brain (plasma Tmax: 1 h, Cmax: 51.10 ± 13.51 ng/ml; Brain Tmax: 0.5 h, Cmax: 22.54 ± 4.08 ng/ml). We further determined the in-vivo effect of 5j on cognition in scopolamine-induced amnesia in C57BL/6j mice. We observed that 5j (10 mg/kg, p.o) alleviated scopolamine-induced impairment in short-term memory and social recognition, which were blocked by D1/D5 antagonist SCH23390 (0.1 mg/kg, i.p.). Furthermore, 5j did not exhibit any cytotoxicity (up to 10 µM) or in vivo acute toxicity up to 200 mg/kg (p.o). These results strongly suggest that 5j could be further developed for treating neurological disorders wherein the D5 receptors play pivotal roles.

Unveiling a New Antimicrobial Peptide with Efficacy against P. aeruginosa and K. pneumoniae from Mangrove-Derived Paenibacillus thiaminolyticus NNS5-6 and Genomic Analysis.

This study focused on the discovery of the antimicrobial peptide (AMP) derived from mangrove bacteria. The most promising isolate, NNS5-6, showed the closest taxonomic relation to Paenibacillus thiaminolyticus, with the highest similarity of 74.9%. The AMP produced by Paenibacillus thiaminolyticus NNS5-6 exhibited antibacterial activity against various Gram-negative pathogens, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. The peptide sequence consisted of 13 amino acids and was elucidated as Val-Lys-Gly-Asp-Gly-Gly-Pro-Gly-Thr-Val-Tyr-Thr-Met. The AMP mainly exhibited random coil and antiparallel beta-sheet structures. The stability study indicated that this AMP was tolerant of various conditions, including proteolytic enzymes, pH (1.2-14), surfactants, and temperatures up to 40 °C for 12 h. The AMP demonstrated 4 µg/mL of MIC and 4-8 µg/mL of MBC against both pathogens. Time-kill kinetics showed that the AMP acted in a time- and concentration-dependent manner. A cell permeability assay and scanning electron microscopy revealed that the AMP exerted the mode of action by disrupting bacterial membranes. Additionally, nineteen biosynthetic gene clusters of secondary metabolites were identified in the genome. NNS5-6 was susceptible to various commonly used antibiotics supporting the primary safety requirement. The findings of this research could pave the way for new therapeutic approaches in combating antibiotic-resistant pathogens.

Flux vacua in type IIB compactifications on orbifolds: their finiteness and minimal string coupling

We perform a detailed study of (supersymmetric) moduli stabilisation in type IIB toroidal orientifolds with fluxes. We provide strong evidence towards exhaustion of the finite number of inequivalent vacua for a given total 3-form flux charge Nflux. We also find that the minimal value of the string coupling gs is given in terms of Nflux and present strong evidence for the asymptotic relation gs, min ∼ c/Nfluxα\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ c/{N}_{\ extrm{flux}}^{\\alpha } $$\\end{document}, with α = 1, 2, valid for not too small Nflux, where c is an order 1 coefficient and α depends on the orbifold. Imposing tadpole cancellation, Nflux is bounded from the number of orientifold O3-planes. Combined with the flux quantisation, this forbids orientifold vacua without anti-brane charge. On the other hand, the presence of negative D3-brane charge induced by magnetised D7-branes breaks supersymmetry and relaxes the bound, allowing significantly smaller values for gs.

Characterization and Evaluation of the Cytotoxicity of Pregabalin Gels for Oral Application.

The efficacy of pregabalin in pain treatment has led to the search for new formulations for its use through different routes of administration. This study aimed to prepare, characterize, and evaluate the cytotoxicity of pregabalin (PG) gels for topical application in the oral cavity. Solutions with three different concentrations of PG were prepared and added to a 1.0% carbopol gel base. Thermal analyses (TG and DSC) and FTIR were performed on the gel and pure pregabalin. Stability (preliminary and accelerated) and rheology studies were also conducted on the gels. Cytotoxicity was evaluated in human gingival fibroblasts in the following groups: WG (1.0% carbopol gel base), PG2G (2.0% pregabalin gel), PG5G (5.0% pregabalin gel), and PG10G (10% pregabalin gel). A transparent and homogeneous gel with a pH of 6 was obtained. The formulations showed stability, and the different drug concentrations did not influence the product's characteristics. None of the tested groups showed cytotoxicity for the analyzed cells. The pregabalin gels exhibited favorable and non-toxic characteristics for human gingival fibroblasts in vitro. Therefore, this product may be a promising therapeutic alternative for topical application in the oral mucosa.