Diffusion Profiles Research Articles

Formulation of chitosan based lipid polymer hybrid nanocarrier system for oral delivery of tamoxifen citrate: Toxicological and hemocompatibility evaluation

The objective of the current work was to develop chitosan based lipid nanocarriers for the oral controlled release of tamoxifen citrate (TC). The ionic gelation method was used to develop various formulations with altered ratios of polymer, lipid, and emulsifier. The developed lipid hybrid nanoparticles (LHNPs) were characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, SEM, DSC, FTIR, PXRD, in vitro release studies, stability studies, kinetic modeling, toxicity studies, and hemocompatibility assay. Particle size and entrapment efficiency of the developed formulations varied between 138.2 ± 4.2 nm to 281.8 ± 63.1 nm and 70.94 ± 0.29 % to 82.23 ± 0.02 %, respectively. The polydispersity index and zeta potential ranged from 0.199 ± 0.03 to 0.555 ± 0.01 and 17.9 ± 0.62 to 32.3 ± 0.36, respectively. Nano-sized, spherical in shape surfaces of developed particles were depicted by SEM. While removal of TC melting endotherm revealed by DSC analysis, suggested good thermal stability of LHNPs. FTIR verified that the components of the formulation do not interact chemically. PXRD depicted that the developed formulation has been successfully amorphized. In vitro release study revealed drug release, an initial burst drug release followed by the controlled release up to 72 h. Kinetic modeling exposed that all developed formulations showed a non-Fickian diffusion profile and were best fitted into Higuchi's square root and Korsmeyer-Peppas models. Toxicity investigations on female albino rabbits provided evidence for the compatibility and non-toxicity of developed particles with biological systems. Hemocompatibility assay showed that the developed system is compatible with blood and nontoxic. These investigations demonstrate the potential of developed LHNPs as a vehicle, aimed at controlled oral delivery of TC for better therapeutic applications in breast cancer.

Li–Na interdiffusion and diffusion-driven lithium isotope fractionation in pegmatitic melts

Abstract. In this study, we investigate the diffusion of Li and its stable isotopes (6Li and 7Li) in flux-rich (1.8 % Li2O, 2.6 % B2O3, 2.3 % P2O5 and 3 % F) pegmatitic melts in order to contribute to the understanding of Li enrichment in such systems. Two glasses were synthesized with a model pegmatitic composition, one of which is highly enriched in Li (> 1 wt %, PEG2-blue) and the other one essentially Li-free (PEG2-Li-free). Diffusion couple experiments were performed to determine the chemical diffusivity of Li in dry pegmatitic melts. Experiments were conducted using rapid-heat and rapid-quench cold-seal pressure vessels in a temperature range of 650–940 ∘C at 100 MPa with Ar as the pressure medium. We observed rapidly formed diffusion profiles, driven by an interdiffusive exchange of the monovalent alkalis Li and Na, while the other elements are immobile on the timescale of experiments (1–30 min). From these experiments, activation energies for Li–Na interdiffusion were determined as 99 ± 7 kJ mol−1 with a pre-exponential factor of log D0 = −5.05 ± 0.33 (D0 in m2 s−1). Li and Na partitioning between the stronger depolymerized PEG2-blue and the less depolymerized PEG2-Li-free leads to a concentration jump at the interface; i.e. Na is enriched in the more depolymerized PEG2-blue. Li–Na interdiffusion coefficients in the studied melt composition are in a similar range as Li and Na tracer diffusivities in other dry aluminosilicate melts, confirming little to no effect of aluminosilicate melt composition on Li diffusivity. Thus, added fluxes do not enhance the Li diffusivity in the same way as observed for H2O (Holycross et al., 2018; Spallanzani et al., 2022). Using melt viscosity as a proxy for the polymerization of the melt shows that water has a stronger potential to depolymerize a melt compared to other fluxing elements. Faster diffusion of 6Li compared to 7Li leads to a strong Li isotope fractionation along the diffusion profile, resulting in δ7Li as low as −80 ‰ relative to the diffusion-unaffected regions. This diffusive isotope fractionation can be quantified with an empirical isotope fractionation factor (β) of 0.20 ± 0.04, similar to previously observed β values for Li diffusion in melts. This suggests in accordance with previously published data that a β value of ca. 0.2 seems to be universally applicable to diffusive Li isotope fractionation in aluminosilicate melts.

Thermodynamic Assessment of the Fe–Mn–Ni System and Diffusion Mobility of Its Face-Centered Cubic Phase

Through extrapolation of updated binary descriptions, the Fe–Mn–Ni system was thermodynamically elucidated in a self-consistent way. The obtained thermodynamic description was confirmed to be reliable by measuring phase equilibria at relatively low temperatures. Our current thermodynamic evaluation can describe the phase stabilities over a wide temperature range and provide a reliable thermodynamic factor for the diffusion mobility optimization. For the face-centered cubic (FCC) phase in the investigated alloy system, optimization of diffusion mobilities was accomplished with the CALPHAD method. Interdiffusivities were extracted based on the composition-distance profiles of diffusion couples investigated herein. Through comprehensive diffusion behavior comparisons, our proposed diffusion mobilities were confirmed.

Not Just Contrastive: Constructions with Negated Restrictives in English

When restrictive adverbs are negated, an additive reading is produced (e.g., not only). This is particularly common in correlative constructions with a corrective part optionally introduced by but (e.g., not just in England but also in Scotland), but can also appear in other syntactic contexts. This study investigates formal and functional variation in the use of the four most common variants of negated restrictives ( not only, not just, not simply, and not merely) from the perspective of constructional and usage-based approaches to language. The study is based on a dataset of 1599 tokens, annotated for formal, functional, and extralinguistic variables, and is analyzed using hierarchical configural frequency analysis. The contrastive correlative construction not only X but ( also) Y appears as the central grammatical context for negated restrictives in English. In addition to its high frequency, not only displays the least variability in both form and function, which suggests a high degree of conventionalization. The less frequent variants of negated restrictives have more diffuse usage profiles, suggesting they are less conventionalized and may be emergent constructions which have not yet conventionalized into stable parts of the language. Methodologically, the study suggests an alternative to modeling alternations, which enables the detection of different degrees of conventionalization and which avoids conceptualizing alternations as choices conditioned by independent variables.

Ozone in the boreal forest in the Alberta Oil Sands Region

Abstract. Measurements of ozone were made using an instrumented tower and a tethersonde located in a forested region surrounded by oil sands production facilities in the Athabasca Oil Sands Region (AOSR). Our observations and modeling show that the concentration of ozone was modified by vertical mixing, photochemical reactions, and surface dry deposition. Measurements on the tower demonstrated that when winds are from the direction of anthropogenic emissions from oil sand extraction and processing facilities, there is no significant increase in ozone mixing ratio compared to when winds are from the direction of undisturbed forest. This suggests that ozone is destroyed by reaction with NOx from oil sands extraction operations (as well as NO resulting from photolysis of NO2). Vertical gradients of ozone mixing ratio with height were observed using instruments on a tethered balloon (up to a height of 300 m) as well as a pulley system and two-point gradients within the canopy. Strong gradients (ozone increasing with height near 0.35 ppb m−1) were measured in the canopy in the evening and overnight, while morning and daytime gradients were weaker and highly variable. A 1D canopy model was used to simulate the diurnal variation of the in-canopy gradient. Model results suggest an ozone dry deposition velocity between 0.2 and 0.4 cm s−1 for this location. Sensitivity simulations using the model suggest that the local NO concentration profile and coefficients of vertical diffusivity have a significant influence on the O3 concentrations and profiles in the region.

In silico investigation to optimize the convection-enhanced diffusion profile with directed extraction

In silico investigation to optimize the convection-enhanced diffusion profile with directed extraction

Diffuse interface method for solid composite propellant ignition and regression

Solid Composite Propellants (SCPs) are extensively used in the field of propulsion for their chemical and mechanical stability in long-term storage, and for having simple production and operation processes. Computational modeling enables cost reduction, increased efficiency, and greater coverage of the configuration space in the SCP design process. However, accurate and efficient SCP modeling presents a number of numerical challenges. A primary obstacle in modeling these systems is capturing the complex evolving interface. Recently, it has been shown that the phase-field method has a strong ability to model the combustion behavior of SCPs, implicitly capturing the topological evolution at a relatively low computational cost. Initial phase-field methods show promise in their ability to do predictive regression modeling but require a number of approximations and heuristic modeling methods. This work presents a new formulation for the phase field regression model that combines a thermal solver with an Arrhenius rate law to model interface regression using a comprehensive and physics-based approach. This improves the capability of previous methods by increasing the number of kinematic forces that are accounted for, and allowing the study of thermal diffusivity in the system. It also enables the integration of a fully coupled solid-fluid interface. To demonstrate the efficacy of the model, it is applied and calibrated to a homogeneous monopropellant (ammonium perchlorate). The model is validated for a range of temperatures, with a reasonable quantitative match to experimental data. It was also demonstrated that the model recovered the relationship between ignition time and heat flux, with no fitting required. Overall, the method showed great capability of reproducing experimental data by matching temperature, burn rate, and thermal diffusivity profiles. Statement of SignificanceA new diffuse interface method is developed for calculating ignition and regression rates in SCPs. While this builds on previous work in diffuse interface modeling of SCPs, it is novel in its coupling to thermal transport, as well as its development of (and coupling to) a approximation for gas phase heat flux. The model is shown to reproduce experimental regression rate data with reasonable accuracy. Moreover, it quantitatively captures ignition behavior with no additional modifications to the model. The model is implemented in a high performance computational framework that is able to resolve large, three-dimensional mesostuctures.

Research Progress in Diffusion Spectrum Imaging.

Studies have demonstrated that many regions in the human brain include multidirectional fiber tracts, in which the diffusion of water molecules within image voxels does not follow a Gaussian distribution. Therefore, the conventional diffusion tensor imaging (DTI) that hypothesizes a single fiber orientation within a voxel is intrinsically incapable of revealing the complex microstructures of brain tissues. Diffusion spectrum imaging (DSI) employs a pulse sequence with different b-values along multiple gradient directions to sample the diffusion information of water molecules in the entire q-space and then quantitatively estimates the diffusion profile using a probability density function with a high angular resolution. Studies have suggested that DSI can reliably observe the multidirectional fibers within each voxel and allow fiber tracking along different directions, which can improve fiber reconstruction reflecting the true but complicated brain structures that were not observed in the previous DTI studies. Moreover, with increasing angular resolution, DSI is able to reveal new neuroimaging biomarkers used for disease diagnosis and the prediction of disorder progression. However, so far, this method has not been used widely in clinical studies, due to its overly long scanning time and difficult post-processing. Within this context, the current paper aims to conduct a comprehensive review of DSI research, including the fundamental principles, methodology, and application progress of DSI tractography. By summarizing the DSI studies in recent years, we propose potential solutions towards the existing problem in the methodology and applications of DSI technology as follows: (1) using compressed sensing to undersample data and to reconstruct the diffusion signal may be an efficient and promising method for reducing scanning time; (2) the probability density function includes more information than the orientation distribution function, and it should be extended in application studies; and (3) large-sample study is encouraged to confirm the reliability and reproducibility of findings in clinical diseases. These findings may help deepen the understanding of the DSI method and promote its development in clinical applications.

Effect of heterogeneity on the diffusion of Pb in apatite for petrochronological applications: A multiscale approach to characterizing the influence of apatite chemistry and anisotropy on Pb diffusion

The investigation of various factors effecting the Lead (Pb) diffusion in phosphate minerals such as apatite is still challenging in the interpretation of (UTh)/Pb geochronology. For (UTh)/Pb system, apatite minerals have closure temperatures in the range of 375 to 600 °C and therefore can be used for the investigation of mid-temperature thermochronological and/or petrochronological questions i.e., the reconstruction of thermal events in Earth's crust. There is still uncertainty whether Pb diffusion in apatite is characterized by thermally activated volume and/or anisotropic diffusion profiles or is instead impacted by novel growth processes and recrystallization (chemical substitutions). As the apatite structure support extensive compositional variability, including partial or total substitution of both the cationic and anionic sites and forms solid solutions therefore, it necessitates a thorough examination of these effects and anisotropy on Pb diffusivity and (UTh)/Pb geochronometric system. For this, a multi-scale study is carried out to examine the effects of chemical composition, anisotropy, and growth structure on the diffusion of Pb in order to better understand the behaviour of Pb diffusion in apatite. This study employed computational techniques like Density Functional Theory (DFT) and Transition State Theory (TST) at the atomic level and integrates it with the Kinetic Monte Carlo (KMC) simulations at the macroscopic level. Models of this study shows that Pb diffusion is completely anisotropic along the preferred z-axis or [001] direction and Pb readily escapes faster from Na-substituted apatite when compared to pure F-apatite and Cl-substituted apatite. Because of this anisotropy and chemical substitutions, Pb diffusivity in apatite either increases by opening of diffusion channels or decreases by blocking the diffusion channels depending on the site and type of chemical substitution. Further, in case of blocking effect the Pb diffusion occurs through workaround pathways and approaches towards the isotropic diffusion. For Na-substituted apatite, the impact of Na occupation on anisotropic Pb diffusion is significantly greater while in case of Cl-substituted apatite the Cl occupation mostly leads towards isotropic diffusion by opening the diffusion paths along other directions (mostly along the in-plane direction). Furthermore, the high closure temperatures (Tc) (e.g., ∼1370 °C) of the modelled apatites (except the perfect Na-substituted apatite e.g., ∼500 °C) of this study when compared to the Tc of Durango apatite obtained experimentally for the effective grain size of 100 μm and cooling rates of 10 °C/Ma indicate that the effective closure temperature dominantly depends on the degree and types of chemical substitutions and play a crucial role for the closure or opening of Pb diffusion/loss in apatites.

Uranium–plutonium–americium cation interdiffusion in polycrystalline (U,Pu,Am)O2±x mixed oxides

Diffusion couples made of dense polycrystalline U1−αPuα−βAmβO2±γ/U1−yPuy−zAmzO2±x oxides were annealed in various thermodynamic conditions (temperature, oxygen partial pressure), and for different durations. The associated actinide redistribution was quantified using Electron Probe Micro-Analysis (EPMA). Average diffusion profiles were obtained from elemental U, Pu, and Am X-ray maps and the resulting interdiffusion coefficients were calculated, then analyzed at the light of our model of point defect chemistry.

Passive permeability controls synthesis for the allelochemical sorgoleone in sorghum root exudate

Competition for soil nutrients and water with other plants foster competition within the biosphere for access to these limited resources. The roots for the common grain sorghum produce multiple small molecules that are released via root exudates into the soil to compete with other plants. Sorgoleone is one such compound, which suppresses weed growth near sorghum by acting as a quinone analog and interferes with photosynthesis. Since sorghum also grows photosynthetically, and may be susceptible to sorgoleone action if present in tissues above ground, it is essential to exude sorgoleone efficiently. However, since the P450 enzymes that synthesize sorgoleone are intracellular, the release mechanism for sorgoleone remain unclear. In this study, we conducted an in silico assessment for sorgoleone and its precursors to passively permeate biological membranes. To facilitate accurate simulation, CHARMM parameters were newly optimized for sorgoleone and its precursors. These parameters were used to conduct 1 μs of unbiased molecular dynamics simulations to compare the permeability of sorgoleone with its precursors molecules. We find that interleaflet transfer is maximized for sorgoleone, suggesting that the precursor molecules may remain in the same leaflet for access by biosynthetic P450 enzymes. Since no sorgoleone was extracted during unbiased simulations, we compute a permeability coefficient using the inhomogeneous solubility diffusion model. The requisite free energy and diffusivity profiles for sorgoleone through a sorghum membrane model were determined through Replica Exchange Umbrella Sampling (REUS) simulations. The REUS calculations highlight that any soluble sorgoleone would quickly insert into a lipid bilayer, and would readily transit. When sorgoleone forms aggregates in root exudate as indicated by our equilibrium simulations, aggregate formation would lower the effective concentration in aqueous solution, creating a concentration gradient that would facilitate passive transport. This suggests that sorgoleone synthesis occurs within sorghum root cells and that sorgoleone is exuded by permeating through the cell membrane without the need for a transport protein once the extracellular sorgoleone aggregate is formed.

Single Microcolony Diffusion Analysis in Pseudomonas aeruginosa Biofilms.

Diffusion phenomena play an important role during various stages of biofilm development. Hence, quantification of the diffusion coefficient of molecules provides important information necessary to understand the variability in diffusion profiles at different biofilm stages. Imaging fluorescence correlation spectroscopy (FCS) enables the visualization of 3D diffusion profiles of biofilms. In this protocol, we explain how to grow biofilms for investigation using imaging FCS and how to acquire and analyze the data.

Transient magnetized Soret effect on dissipative couple stress convection flow past a cylinder

The current article aims to reveal the thermal characteristics of dissipative magnetized chemically reactive unsteady couple stress convection along a cylinder with radiation, heat source/sink, and Soret influences. Governing partial differential equations (PDEs) are produced based on considered physical situation and geometry. Resultant Navier–Stokes equations (NS-E) are highly non-linear, coupled in nature. Analytical techniques fail to find the solutions of these resultant NS-equations. The discretized algebraic NS equations are solved by applying Crank–Nicolson numerical scheme through pentadiagonal and tridiagonal algorithms. Also, the flow of couple stress fluid with physical effects gives a 4th order PDE which needs pentadiagonal algorithm to solve it. Implementing this algorithm numerically is challenging and it is worthy to investigate to analyze the flow behavior. Hence, the simulated couple stress fluid velocity, energy, and mass diffusion profiles including engineering quantities of interest in the boundary layer region are discussed for different parametric values. Contemporary exploration illustrates that magnifying the buoyancy ratio parameter enhances the velocity field. Thermal field elevated for higher values of energy source/sink number. Also, contour plots of velocity, temperature, and mass diffusion profiles have been drawn in the vicinity of a cylinder. In addition, the range of control parameters performed in this study are = 0.00.6, = 0.2 0.8, = 0.00.3, = 0.10.4, and = 1.04.0. Finally, investigated dimensionless outcomes are verified with available solutions and got good agreement.

Parameterizing Vertical Mixing Coefficients in the Ocean Surface Boundary Layer Using Neural Networks

AbstractVertical mixing parameterizations in ocean models are formulated on the basis of the physical principles that govern turbulent mixing. However, many parameterizations include ad hoc components that are not well constrained by theory or data. One such component is the eddy diffusivity model, where vertical turbulent fluxes of a quantity are parameterized from a variable eddy diffusion coefficient and the mean vertical gradient of the quantity. In this work, we improve a parameterization of vertical mixing in the ocean surface boundary layer by enhancing its eddy diffusivity model using data‐driven methods, specifically neural networks. The neural networks are designed to take extrinsic and intrinsic forcing parameters as input to predict the eddy diffusivity profile and are trained using output data from a second moment closure turbulent mixing scheme. The modified vertical mixing scheme predicts the eddy diffusivity profile through online inference of neural networks and maintains the conservation principles of the standard ocean model equations, which is particularly important for its targeted use in climate simulations. We describe the development and stable implementation of neural networks in an ocean general circulation model and demonstrate that the enhanced scheme outperforms its predecessor by reducing biases in the mixed‐layer depth and upper ocean stratification. Our results demonstrate the potential for data‐driven physics‐aware parameterizations to improve global climate models.

Robust Estimation of Position-Dependent Anisotropic Diffusivity Tensors from Molecular Dynamics Trajectories.

Confinement breaks translational and rotational symmetry in materials and makes all physical properties functions of position. Such spatial variations are key to modulating material properties at the nanoscale, and characterizing them accurately is therefore an intense area of research in the molecular simulations community. This is relatively easy to accomplish for basic mechanical observables. Determining spatial profiles of transport properties, such as diffusivity, is, however, much more challenging, as it requires calculating position-dependent autocorrelations of mechanical observables. In our previous paper (Domingues, T.S.; Coifman, R.; Haji-Akbari, A. J. Phys. Chem. B 2023, 127, 5273 10.1021/acs.jpcb.3c00670), we analytically derive and numerically validate a set of filtered covariance estimators (FCEs) for quantifying spatial variations of the diffusivity tensor from stochastic trajectories. In this work, we adapt these estimators to extract diffusivity profiles from MD trajectories and validate them by applying them to a Lennard-Jones fluid within a slit pore. We find our MD-adapted estimator to exhibit the same qualitative features as its stochastic counterpart, as it accurately estimates the lateral diffusivity across the pore while systematically underestimating the normal diffusivity close to hard boundaries. We introduce a conceptually simple and numerically efficient correction scheme based on simulated annealing and diffusion maps to resolve the latter artifact and obtain normal diffusivity profiles that are consistent with the self-part of the van Hove correlation functions. Our findings demonstrate the potential of this MD-adapted estimator in accurately characterizing spatial variations of diffusivity in confined materials.

Sonochemical synthesis of γ-CD-MOFs microcapsule for myricetin delivery: Study of adsorption mechanism, molecular simulation, solubility, antioxidation, biocompatibility, and in vitro digestion

Improving the bioavailability of myricetin and thus enlarging its commercial utilization have always been highly desirable. γ-cyclodextrin (γ-CD) based metal organic frameworks (γ-CD-MOFs) has provided novel technological opportunities for pharmaceutical and nutraceutical delivery, as credited by its recognized adsorption property and renewable nature. Here, we proposed a facile way of preparing uniform γ-CD-MOFs with mono-dispersity (14.24 ± 1.39 μm) and high-yield (84.74 ± 2.30%) by using ultrasonic-assisted synthetic method for myricetin loading and delivery. The generated γ-CD-MOFs showed excellent loading capacity via stepwise adsorbing myricetin within its diverse pores. Adsorption kinetics analysis confirmed the significance of chemisorption effects during the adsorption process, and diffusion model was utilized to clarify the diffusion profile of myricetin into γ-CD-MOFs in detail. The tandem of experimental (SEM, XRD, DSC, TG, BET, FT-IR) and computational (MD simulations) approaches allowed us to identify the presence status and intermolecular interactions of encapsulated myricetin, as well as the adsorption mechanism. γ-CD-MOFs displayed superior capacity to solubilize myricetin as reflected by the enhanced solubility and dissolution rate in comparison to the single γ-CD encapsulation. The improved solubility also considerably contributed to the enhanced antioxidant activity of myricetin-loaded γ-CD-MOFs. In vitro digestion simulation and cell cytotoxicity results further showed that γ-CD-MOFs encapsulation could achieve controlled release of myricetin with satisfactory bioavailability. This work highlights a facile way for constructing cyclodextrin-based MOFs and prompting further practical application of myricetin or other hydrophobic nutrients.

Structural Fingerprinting of the Frontal Aslant Tract: Predicting Cognitive Control Capacity and Obsessive-Compulsive Symptoms.

White matter of the human brain is influenced by common genetic variations and shaped by neural activity-dependent experiences. Variations in microstructure of cerebral white matter across individuals and even across fiber tracts might underlie differences in cognitive capacity and vulnerabilities to mental disorders. The frontoparietal and cingulo-opercular networks of the brain constitute the central system supporting cognitive functions, and functional connectivity of these networks has been used to distinguish individuals known as "functional fingerprinting." The frontal aslant tract (FAT) that passes through the two networks has been implicated in executive functions. However, whether FAT can be used as a "structural fingerprint" to distinguish individuals and predict an individual's cognitive function and dysfunction is unknown. Here we investigated the fingerprinting property of FAT microstructural profiles using three independent diffusion MRI datasets with repeated scans on human participants including both females and males. We found that diffusion and geometric profiles of FAT can be used to distinguish individuals with a high accuracy. Next, we demonstrated that fractional anisotropy in different FAT segments predicted distinct cognitive functions, including working memory, inhibitory control, and relational reasoning. Finally, we assessed the contribution of altered FAT microstructural profiles to cognitive dysfunction in unmedicated patients with obsessive-compulsive disorders. We found that the altered microstructure in FAT was associated with the severity of obsessive-compulsive symptoms. Collectively, our findings suggest that the microstructural profiles of FAT can identify individuals with a high accuracy and may serve as an imaging marker for predicting an individual's cognitive capacity and disease severity.SIGNIFICANCE STATEMENT The frontoparietal network and cingulo-opercular network of the brain constitute a dual-network architecture for human cognitive functions, and functional connectivity of these two networks can be used as a "functional fingerprint" to distinguish individuals. However, the structural underpinnings of these networks subserving individual heterogeneities in their functional connectivity and cognitive ability remain unknown. We show here that the frontal aslant tract (FAT) that passes through the two networks distinguishes individuals with a high accuracy. Further, we demonstrate that the diffusion profiles of FAT predict distinct cognitive functions in healthy subjects and are associated with the clinical symptoms in patients with obsessive-compulsive disorders. Our findings suggest that the FAT may serve as a unique structural fingerprint underlying individual cognitive capability.

Study on Sulfamethoxazole-Piperazine Salt: A Mechanistic Insight into Simultaneous Improvement of Physicochemical Properties.

Multidrug salts represent more than one drug in a crystal lattice and thus could be used to deliver multiple drugs in a single dose. It showcases unique physicochemical properties in comparison to individual components, which could lead to improved efficacy and therapeutic synergism. This study presents the preparation and scale-up of sulfamethoxazole-piperazine salt, which has been thoroughly characterized by X-ray diffraction and thermal and spectroscopic analyses. A detailed mechanistic study investigates the impact of piperazine on the microenvironmental pH of the salt and its effect on the speciation profile, solubility, dissolution, and diffusion profile. Also, the improvement in the physicochemical properties of sulfamethoxazole due to the formation of salt was explored with lattice energy contributions. A greater ionization of sulfamethoxazole (due to pH changes contributed by piperazine) and lesser lattice energy of sulfamethoxazole-piperazine contributed to improved solubility, dissolution, and permeability. Moreover, the prepared salt addresses the stability issues of piperazine and exhibits good stability behavior under accelerated stability conditions. Due to the improvement of physicochemical properties, the sulfamethoxazole-piperazine salt demonstrates better pharmacokinetic parameters in comparison to sulfamethoxazole and provides a strong suggestion for the reduction of dose. The following study suggests that multidrug salts can concurrently enhance the physicochemical properties of drugs and present themselves as improved fixed-dose combinations.

Effect of creep loading on the oxygen diffusion of Ti6242S at 650°C

The influence of low and steady loading on the oxidation behaviour and oxygen diffusion within Ti6242S was investigated at 650 °C in air. Electron probe microanalyser (EPMA), secondary-ion mass spectrometry (SIMS) and high energy synchrotron X-ray diffraction (S-XRD) were used to quantify the oxygen distribution within the oxygen-enriched layer beneath the external oxide scale. Rietveld and peak by peak methods were used to evaluate the average response versus the crystal-oriented response of this diffusion process under load. Interestingly, a thermo-mechano-chemical coupling occurs during the creep-oxidation experiment even for moderate applied stresses (25-70 MPa) and demonstrates: (i) a decrease of the oxygen concentration at the metal/oxide interface, and (ii) a curvature change of the oxygen diffusion profile with load application. A qualitative thermo-mechano-chemical approach is proposed to model the modification of the diffusion law of the oxygen within Ti6242S due to application of a mechanical loading to explain observed experimental results.

Electrochemical investigation on calcium ion sensing and steady-state diffusion analysis using zinc oxide modified glassy carbon electrode

The concentration of calcium ions in human blood serum typically falls within a narrow range of 2 and 2.5 mmol/L. However, hyperthyroidism, resulting from an overactive parathyroid gland, can lead to an elevation of calcium ion concentration beyond 2.5 mmol/L, necessitating the development of a highly sensitive and selective electrochemical sensor for calcium ion detection. To address this issue, a highly sensitive and selective electrochemical sensor based on zinc oxide nanoparticles-chitosan composite modified glassy carbon electrode (GC/ZnO-Chitosan) was fabricated for the detection of calcium ions. Cyclic voltammetric analysis revealed that the fabricated electrode possesses excellent electrocatalytic activity for calcium ion oxidation and reduction. The fabricated electrode showed high sensitivity (449.887 µA mM−1) towards calcium ions over the wide detection range of 2.14–3.5 mM with a low detection limit of 2.26 µM, and a low quantification limit of 7.45 µM. Moreover, the fabricated electrode showed fast response time (<25 s) due to the synergistic effect of enhanced adsorption of calcium ions (Γ=2.17×10-7 mol cm−2), efficient electron shuttling capacity of ZnO nanoparticles between GCE (ks=6.01 s−1) and the adsorbed calcium ions, and enhanced diffusion of calcium ions (DCa2+=1.2788×10-6cm2s-1) within the ZnO-Chitosan composite film. Genocchi polynomial approximation method was employed for the establishment of a precise mathematical relationship between the steady-state concentration of calcium ions and the distance from the electrode's surface. This newly developed GC/ZnO-Chitosan electrode presents a significant improvement over previously developed electrodes for calcium ions, as it enables the precise analysis of calcium ion diffusion profiles at steady-state.