Search Results (226)

In a previous article, an estimation procedure for calculating the liquidus and solidus lines of binary equilibrium phase diagrams was presented. In this article, keeping the thermodynamic basics, the estimation method for the approximate calculation of the liquidus and solidus surfaces of ternary phase diagrams was further developed. It is shown that the procedure has a hierarchical structure, and the ternary functions contain the binary functions. The applicability of the method is checked by calculating the liquidus and solidus surfaces of the Ag-Au-Pd isomorphous ternary equilibrium phase diagram. The application of each level of the developed four-level procedure depends on the data available and the aim. It is shown that in the case of a concentration range close to the base alloy pure element, the liquidus and solidus surfaces of the ternary equilibrium phase diagram can be calculated from the liquidus and solidus functions of the binary equilibrium phase diagrams with a few K errors, which is 0.2 at% at 10 K/at% slope. The equilibrium phase diagrams were available in graphical form, so the data obtained via digitalisation of the diagrams for the calculations was used. The functions describe the slope of the surfaces, and the approximate method developed for the calculation of the partition ratios is also shown. Full article

The Aptian–Albian interval represents a significant cooling phase within the Cretaceous “hothouse” climate, marked by dynamic climatic fluctuations. High-resolution continental records are essential for reconstructing terrestrial climate and ecosystem evolution during this period. This study examines a lacustrine-dominated succession of the Shahezi Formation (Lishu Rift Depression, Songliao Basin, NE Asia) to access paleo-weathering intensity and paleoclimate variability between the Middle Aptian and Early Albian (c. 118.2–112.3 Ma). Multiple geochemical proxies, including the Chemical Index of Alteration (CIA), were applied within a sequence stratigraphic framework covering four stages of lake evolution. Our results indicate that a hot and humid subtropical climate predominated in the Lishu paleo-lake, punctuated by transient cooling and drying events. Periods of lake expansion corresponded to episodes of intense chemical weathering, while two distinct intervals of aridity and cooling coincided with phases of a reduced lake level and fan delta progradation. To address the impact of potassium enrichment on CIA values, we introduced a rectangular coordinate system on A(Al₂O₃)-CN(CaO* + Na₂O)-K(K₂O) ternary diagrams, enabling more accurate weathering trends and CIA corrections (CIA_corr). Uncertainties in CIA correction were evaluated by integrating geochemical and petrographic evidence from deposits affected by hydrothermal fluids and external potassium addition. Importantly, our results show that metasomatic potassium addition cannot be reliably inferred solely from deviations in A-CN-K diagrams or the presence of authigenic illite and altered plagioclase. Calculations of “excess K₂O” and CIA_corr values should only be made when supported by robust geochemical and petrographic evidence for external potassium enrichment. This work advances lacustrine paleoclimate reconstruction methodology and highlights the need for careful interpretation of weathering proxies in complex sedimentary systems. Full article

Objectives: Drug–drug cocrystallization represents a promising approach for the development of novel combination drugs with improved physicochemical and biopharmaceutical properties. The aim of the present research is to prepare novel drug-drug cocrystalline forms of antiepileptic drug carbamazepine (CBZ) with sulfacetamide (SCTM). Methods: The novel CBZ cocrystal methanol solvate and cocrystal hydrate were prepared via solvent evaporation technique and characterized by single crystal X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Results: Single-crystal X-ray diffraction and thermal analysis revealed that the multicomponent solids are isostructural, wherein the solvent molecule does not play a structure-forming role. To optimize the synthesis of [CBZ+SCTM+H₂O] (1:1:0.7), the binary and ternary phase diagrams were constructed in acetonitrile at 25 °C. A thorough investigation of the cocrystal hydrate behavior in aqueous solution showed that the pH of the dissolution medium exerted a significant effect on the stability and solubility of [CBZ+SCTM+H₂O] (1:1:0.7). According to the dissolution and diffusion experiments in a buffer solution pH 6.5, the cocrystal hydrate characterized an enhanced dissolution rate and flux of CBZ. Pharmacokinetic studies in rabbits showed that the novel cocrystal hydrate exhibited a comparable bioavailability to the parent CBZ. Conclusions: Overall, this work reports the preparation of a novel CBZ drug-drug cocrystal hydrate, which can be considered as an alternative CBZ solid form for oral usage, possessing additive pharmacological effect. Full article

Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and increased bioavailability of the drug. Methods: The levels of each factor(X) were established using a pseudo-ternary diagram, and the Box-Behnken design (BBD) was used to evaluate the components of oil (18.9 mg), surfactant (70.7 mg), and co-surfactant (10.0 mg) to optimize the SNEDDS formulation. The response(Y) considered were particle size, polydispersity index (PDI), transmittance, and stability. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the particle size and morphology. In vitro and ex vivo diffusion tests were conducted to assess drug flux and permeability. Result: Using a response optimization tool, the values of each X factor were optimized to achieve a small particle size (nm), a low polydispersity index (PDI), and high transmittance (%), resulting in a formulation prepared with 18.9 mg of oil, 70.7 mg of surfactant, and 10.0 mg of co-surfactant. The optimized SNEDDS exhibited a small particle size of 24.89 nm, a minimal PDI of 0.068, and a high transmittance of 74.85%. A transmission electron microscopy (TEM) analysis confirmed the presence of uniform spherical nanoemulsion droplets with an observed mean diameter of less than 25 nm, corroborating the dynamic light scattering (DLS) measurements. Furthermore, the SNEDDS demonstrated improved stability under the stress conditions of heating–cooling cycles, with no phase separation, creaming, or caking observed and no differences in its particle size, PDI, or transmittance. In vitro and ex vivo diffusion tests demonstrated that the flux of the optimized SNEDDS (2.723 ± 0.133 mg/cm², 5.446 ± 0.390 μg/cm²) was about 2.5 and 4 times higher than that of the drug dispersion, and the initial diffusion was faster, which is suitable for the characteristics of eye drops. Conclusions: Therefore, the formulation of a flurbiprofen-loaded SNEDDS (FLU-SNE) was successfully optimized using the QbD approach. The optimized FLU-SNE exhibited excellent stability and enhanced permeability, suggesting its potential effectiveness in treating various ocular inflammations, including uveitis and cystoid macular edema. Full article

Zeolite Battery Research Africa (ZEBRA) batteries (Na-NiCl₂ solid electrolyte batteries, SEBs) have commercial applications in energy storage due to their low costs and recyclability, long lifetime, and high safety. In commercial ZEBRA batteries, Ni electrode and beta’’-alumina solid electrolyte (BASE) have a more than 70% share of the overall cell material costs. Na-ZnCl₂ all-liquid batteries (ALBs), which replace Ni with abundant and low-cost Zn and BASE electrolyte with molten salt electrolyte, could reduce costs and provide a longer lifetime and higher safety, making their application in grid storage promising. However, compared to SEBs, ALBs are in an early development stage, particularly for their molten salt electrolytes, which have a significant effect on the battery performance. Physical and chemical properties of the salt electrolyte like melting temperatures and solubilities of electrode materials (i.e., Na and Zn metal) are vital for the molten salt electrolyte selection and battery cell design and optimization. In this work, the binary and ternary phase diagrams of salt mixtures containing NaCl, CaCl₂, BaCl₂, SrCl₂, and KCl, obtained via FactSage simulation and DSC measurements, as well as the solubilities of electrode materials (Na and Zn metals), are presented and used for the selection of the molten salt electrolyte. Moreover, various criteria, considered for the selection of the molten salt electrolyte, include high electromotive force (EMF) for suitable electrochemical properties, low melting temperature for large charge/discharge range, low solubilities of electrode materials for low self-discharge, low material costs, and high material abundance for easy scale-up. Based on these criteria, the NaCl-CaCl₂-BaCl₂ and NaCl-SrCl₂-KCl salt mixtures are selected as the two most promising ALB molten salt electrolytes and suggested to be tested in the ALB demonstrators currently under development. Full article

Objective: This study aimed to develop and characterize the physicochemical properties of a self-emulsion drug delivery system (SNEDDS) incorporating galangal extract (GE) and lemongrass oil (LGO). Then, to develop mouthwash powders containing GE- and LGO-loaded SNEDDS (GL-mouthwash powder) as a promising alternative for preventing and treating denture stomatitis. Methods: The solubility of GE in various vehicles was determined. Subsequently, pseudo-ternary phase diagrams of the different ingredients, oil (LGO), surfactant (Tween^® 80), and co-surfactant (Propylene glycol) were selected to develop the SNEDDS. Then, SNEDDS containing GE and LGO (GL-SNEDDS) were prepared and characterized. The optimized liquid GL-SNEDDS was transformed into GL-mouthwash powder by absorbing onto mannitol and blending with a sweetener. Subsequently, various evaluations including drug recovery, moisture content, emulsification time, stability, anti-Candida activity, and in vitro cytotoxicity were performed. Results: The developed SNEDDS formulation improved GE and LGO solubility. The optimized GL-SNEDDS exhibited a small droplet size of 148.2 ± 2.1 nm with a polydispersity index of 0.11 ± 0.03 and a zeta potential of 2.14 ± 0.11 mV. In addition, the GL-mouthwash powder demonstrated a high drug recovery of >80% with a low moisture of <10% and exhibited greater physicochemical stability under accelerated conditions. The developed GL-mouthwash powder rapidly formed a stable nanoemulsion within 2 min after reconstitution. Interestingly, GL-mouthwash powder exhibited strong anti-Candida activity with no toxicity to human fibroblast cells, which demonstrated superior biocompatibility relative to existing commercial products. Conclusions: These findings suggest that GL-mouthwash powder has potential as an alternative prevention and treatment of oral Candida infection. Full article

Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), mixed surfactants (Labrasol, Tween 80), and a co-surfactant (Transcutol) were selected for the SNEDDS. CBD-loaded SNEDDS formulations were prepared and characterized. The optimal SNEDDS was converted into solid SNEDDS powders via solid carrier adsorption and spray drying techniques. Various evaluations including flowability, drug release, self-emulsifying capacity, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), morphology, and pharmacokinetic characteristics were conducted. Subsequently, the solid powders with fillers, disintegrants, and lubricants were added to the capsules for accelerated stability testing. Results: The investigations showed that the two S-SNEDDS formulations improved the CBD’s solubility and in vitro drug release, with good storage stability. The pharmacokinetic data of Sprague Dawley rats indicated that a single oral dose of L-SNEDDS and spray drying SNEDDS led to a quicker absorption and a higher Cmax of CBD compared to the two oil-based controls (CBD-sesame oil (similar to Epidiolex^®) and CBD-MCT), which is favorable for the application of CBD products. Conclusions: SNEDDS is a prospective strategy for enhancing the solubility and oral bioavailability of CBD, and solid SNEDDS offers flexibility for developing more CBD-loaded solid formulations. Moreover, SNEDDS provides new concepts and methods for other poorly water-soluble drugs. Full article

Background: Despite the rapid development of nanoemulsions in recent years, no method has been established for the preparation of milbemycin oxime nanoemulsions. Milbemycin oxime is a widely used macrolide antibiotic in veterinary medicine, particularly for treating parasitic infections in animals such as dogs. However, its poor solubility in water limits its bioavailability and therapeutic efficacy. Developing a nanoemulsion formulation can enhance its solubility, stability, and bioavailability, offering a more effective treatment option. Methods: In this experiment, oil-in-water (O/W) milbemycin oxime nanoemulsions were successfully prepared by the phase inversion composition (PIC) method using ethyl butyrate as the oil phase, Tween-80 as the surfactant, and anhydrous ethanol as the co-surfactant. The region of O/W nanoemulsions was identified by constructing a pseudo-ternary phase diagram and, based on this, was screened by determining the droplet size, polydispersity coefficient, and zeta potential of each preparation. Results and Conclusions: The finalized formulation had a 2:1 ratio of surfactant to co-surfactant and a 7:3 ratio of mixed surfactant to oil, and its droplet size, polydispersity index (PDI), and zeta potential were 12.140 ± 0.128 nm, 0.155 ± 0.015, and −4.947 ± 0.768 mV, respectively. Transmission electron microscopy confirmed the spherical uniform distribution of droplets, and the nanoemulsions passed thermodynamic stability tests. The in vitro release of milbemycin oxime nanoemulsions followed first-order kinetic equations. In conclusion, nanoemulsions are an interesting option for the delivery of poorly water-soluble molecules such as milbemycin oxime. Full article

The use of Neural Networks in quantum many-body theory has undergone a formidable rise in recent years. Among the many possible applications, their pattern recognition power can be utilized when dealing with the study of equilibrium phase diagrams. Learning by Confusion has emerged as an interesting and unbiased scheme within this context. This technique involves systematically reassigning labels to the data in various ways, followed by training and testing the Neural Network. While random labeling results in low accuracy, the method reveals a peak in accuracy when the data are correctly and meaningfully partitioned, even if the correct labeling is initially unknown. Here, we propose a generalization of this confusion scheme for systems with more than two phases, for which it was originally proposed. Our construction relies on the use of a slightly different Neural Network: from a binary classifier, we move to a ternary one, which is more suitable to detect systems exhibiting three phases. After introducing this construction, we test it on free and interacting Kitaev chains and on the one-dimensional Extended Hubbard model, consistently achieving results that are compatible with previous works. Our work opens the way to wider use of Learning by Confusion, demonstrating once more the usefulness of Machine Learning to address quantum many-body problems. Full article

Background: Silibinin (SLB), a flavonoid derived from milk thistle, exhibits promising therapeutic properties but faces significant clinical limitations due to poor solubility and bioavailability. Objectives: This study focuses on the development and characterization of SLB-loaded nanoemulsions designed for mucosal delivery. Methods: Nanoemulsions were prepared using the spontaneous emulsification method, guided by pseudoternary phase diagrams to determine selected component ratios. Comprehensive characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, rheological properties, and surface tension. Mucoadhesive properties were evaluated using quartz crystal microbalance with dissipation (QCM-D) to quantify interactions with mucin layers. Results: The combination of Capryol 90, Tween 80, and Transcutol in selected proportions yielded nanoemulsions with excellent stability and solubilization capacity, enhancing the solubility of silibinin by 625 times compared to its intrinsic solubility in water. The ternary phase diagram indicated that achieving nanoemulsions with particle sizes between 100 and 300 nm required higher concentrations of surfactants (60%), relative to oil (20%) and water (20%), with formulations predominantly composed of Smix (surfactant and cosurfactant mixture in a 1:1 ratio). Rheological analysis revealed Newtonian behavior, characterized by constant viscosity across varying shear rates and a linear torque response, ensuring ease of application and mechanical stability. QCM-D analysis confirmed strong mucoadhesive interactions, with significant frequency and dissipation shifts, indicative of prolonged retention and enhanced mucosal drug delivery. Furthermore, contact angle measurements showed a marked reduction in surface tension upon interaction with mucin, with the SLB-loaded nanoemulsion demonstrating superior wettability and strong mucoadhesive potential. Conclusions: These findings underscore the suitability of SLB-loaded nanoemulsions as a robust platform for effective mucosal drug delivery, addressing solubility and bioavailability challenges while enabling prolonged retention and controlled therapeutic release. Full article

The RE-M-Ge systems (RE: rare earths, M: transition group elements) contain a large number of compounds with special magnetic properties. A novel compound ErMn₅Ge₃ was found during the investigation on the phase diagram of the Er-Mn-Ge ternary system, and its crystal structure and magnetic properties were investigated. Powder X-ray diffraction results show that ErMn₅Ge₃ crystallizes in an orthorhombic YNi₅Si₃-type structure with the space group Pnma (No. 62) and the lattice parameters of a = 13.0524(6) Å, b = 3.8853(7) Å, and c = 11.4027(4) Å. The magnetization curves and isothermal magnetization curves from 100 to 300 K were measured for ErMn₅Ge₃. Magnetic tests showed that the compound was weakly magnetic and had a Curie temperature of 304 K. It is believed that its magnetic properties are determined by Mn atoms, which are surrounded by a complex environment, leading to uncertainty in the direction of the magnetic moment and hence poor magnetic ordering. This uncertainty simultaneously leads to a significant separation of the ZFC and FZ curves. First-principles calculations confirm that the magnetic properties of ErMn₅Ge₃ are mainly provided by the Mn atoms, and its magnetic moment is calculated to be about 4.5 μ_B. A possible magnetic structure model with simultaneous Mn-Mn ferromagnetic/antiferromagnetic coupling is constructed based on the Mn atom spacing, which can well explain the magnetic performance of ErMn₅Ge₃. Full article

Microemulsions have been commonly used with various permeation enhancers to improve permeability through the skin. The purpose of this study was to compare the release and permeation ability of two commonly used permeation enhancers—diethylene glycol monoethyl ether (DGME) and oleyl alcohol—by the changes in oil composition, the addition of a gelling agent, and water content using ibuprofen as a model drug. Four microemulsions were formulated, selection was based on ternary phase diagrams, and physicochemical properties were evaluated. The release and permeation of the microemulsion formulations were performed in vitro by Franz cell studies on a regenerated cellulose membrane and a Strat-M^® membrane, respectively, and the amount of ibuprofen permeated and released was analyzed by high-performance liquid chromatography (HPLC). All four microemulsions were compatible with the skin pH, and the average pH ranged from 4.9 to 5.6. The average droplet size of the microemulsions ranged from 119.8 to 153.3 nm. Drug release was significantly the highest from the gel-based microemulsions (59% and 64%, p < 0.05). However, there was a fourfold difference in drug permeation from these gels—a significantly higher permeation from the microemulsion-gel containing oleic acid and oleyl alcohol compared to the DGME formulation. These results indicated that the microemulsion-gel with oleyl alcohol as the permeation enhancer could be a preferable formulation approach for the topical administration of ibuprofen. These results highlight the need for optimization of the microemulsion formulation to confirm the permeation-enhancing effects of chosen permeation enhancers despite being a well-known permeation enhancer. Full article

The starting point for the preparation of polymeric membranes by phase inversion is having a thermodynamically stable solution. Ternary diagrams for the polymer, solvent, and non-solvent can predict this stability by identifying the phase separation and describing the thermodynamic behavior of the membrane formation process. Given the lack of data for the ternary system water (H₂O)/hydrochloric acid (HCℓ)/polyamide 66 (PA66), this work employed the Flory–Huggins theory for the construction of the ternary diagrams (H₂O/HCℓ/PA66 and H₂O/formic acid (FA)/PA66) by comparing the experimental data with theoretical predictions. Pure polymer and the membranes produced by phase inversion were characterized to provide the information required to create the ternary diagrams. PA66/FA and PA66/HCℓ solutions were also evaluated regarding their classification as true solutions, and the universal quasi-chemical functional group activity coefficient (UNIFAC) method was used for determining non-solvent/solvent interaction parameters (g₁₂). Swelling measurements determined the polymer/non-solvent interaction parameter (χ₁₃) for H₂O/PA66 and the solvent/polymer interaction parameter (χ₂₃) for PA66/FA and PA66/HCℓ. The theoretical cloud point curve was calculated based on “Boom’s LCP Correlation” and compared to the curve of the experimental cloud point. The ternary Gibbs free energy of mixing and χ₂₃ indicated FA as the best solvent for the PA66. However, for HCℓ, the lower concentration (37–38%), volatility, and fraction volume of dissolved PA66 (ϕ₃) indicated that HCℓ is also adequate for PA66 solubilization based on the similar membrane morphology observed when compared to the PA66/FA membrane. Full article

The phase rule of Gibbs is one of the basic equations in phase equilibria. Although it has been with us for 150 years, discussions, interpretations and extensions have been published. Here, the following new content is provided: (i). the choice of independent components is discussed, and the component rule is introduced, (ii). independent state variables are divided into compositional and non-compositional ones, (iii). the generalized phase rule is derived replacing number two in the original phase rule by the number of independent non-compositional state variables introduced above, (iv). the degree of freedom is decreased by the number of compositional constraints in special points (azeotrope and congruent melting) of phase diagrams, (v). a rule is derived connecting the maximum number of coexisting phases with the dimensions of the phase diagram, (vi). examples show how to apply the phase rule to unary, binary and ternary phase diagrams and their sections, (vii). the same is extended with the discussion of calculable and not calculable phase fractions, (viii). it is shown that the current definition of the degree of freedom is not sufficient in the number of cases, (ix). the current definition of the degree of freedom is extended, (x). the application of the generalized phase rule is demonstrated when other non-compositional state variables are applied for nano-phase diagrams, and/or for phase diagrams under the influence of electric potential difference, external magnetic field, mechanical strain or the gravitational field. Full article

This paper presents equations derived from thermodynamic equations for calculating the liquidus and solidus temperatures, the liquidus slope, and the partition ratio for solidification simulations. The constants of these equations can be easily determined from measurement data obtained by digitalisation from known diagrams or can be calculated using a CALPHAD-based software. ESTPHAD has a hierarchical system; the developed functions of the binary systems are used in the calculation of the functions of the ternary systems, the functions of the ternary systems in the calculation of the function of quaternary systems, and so on. The developed method is demonstrated by processing the liquidus and solidus of Si–Ge isomorphous and Al–Mg and Al–Si eutectic equilibrium phase diagrams. The use of this method for calculating the functions of ternary systems will be shown in Part II. The advantages of this method are that the equations are simple, can be determined very quickly, and can be built into the simulation software very easily. The most significant advantage is that the calculation time is shorter by some order of magnitude than that of a CALPHAD-type calculation. Full article