Search Results (633)

Bicalutamide (BCL), a clinically important non-steroidal antiandrogen, exhibits pronounced conformational polymorphism and complex solid-state behaviour that critically influence its physicochemical and biopharmaceutical properties. This review comprehensively integrates current computational and experimental findings on the structural features, polymorphic forms, and intermolecular stabilisation mechanisms of BCL. Key factors, including torsional flexibility, hydrogen-bond networks, π–π stacking, and fluorine–fluorine contacts, are examined with respect to polymorph stability, solubility, and dissolution kinetics. The review also synthesises recent advances in solid-state optimisation strategies—including co-crystals, solvates, amorphous forms, and solid dispersions—and explores the emerging role of supercritical fluid (SCF) technologies in particle engineering and dissolution enhancement. This work offers a framework for designing next-generation BCL solid forms with enhanced bioavailability and stability by connecting molecular insights with formulation approaches. Full article

Background/Objectives: Prodrug strategies are a vital aspect of drug development, with ester prodrugs particularly notable for modifying parent drug properties through ester functional groups to enhance oral absorption. However, ester prodrugs are prone to hydrolysis by water and enzymes, making stability in the gastrointestinal (GI) tract prior to absorption a key challenge. Few formulation strategies effectively address this degradation issue. We recently introduced binary lipid systems (BLS), comprising a lipid and a water-soluble surfactant only that form stable microemulsions. This study aimed to explore the application of BLS for enhancing the oral absorption of ester prodrugs by coating drug crystals with BLS in solid granules and study the impact of the compositions of BLS on oral absorption. Methods: Olmesartan medoxomil (OLM), a methyl ester prodrug of olmesartan (OL), was selected as a model drug. Various lipids were combined with TPGS to form BLS and used to prepare OLM solid granules containing OLM crystals. Results: Among the tested formulations, OLM MCM-TPGS granules significantly enhanced drug release and protected OLM from enzyme-mediated degradation in two-step dissolution studies with esterase. Pharmacokinetic and tissue distribution studies in rats confirmed that OLM MCM-TPGS granules improved oral absorption by 145% and increased tissue uptake compared to OLM powder. Conclusions: This approach overcomes solubility limitations when using lipids and surfactants as excipients, enabling high drug loading in solid dosage forms and expanding the utility of lipids and surfactants for water-insoluble drugs. This novel formulation strategy holds great potential for enhancing oral absorption of ester prodrugs, representing a significant advancement in formulation technologies and offering more effective and versatile drug delivery solutions. Full article

Pazufloxacin is a fluoroquinolone antibiotic synthesized by Toyama Chemical Co., Ltd. (Tokyo, Japan) in the 1990s. Up until now, the X-ray crystal structure of its mesylate salt had not been determined. The dissolution and recrystallization of pazufloxacin mesylate from different solvents afforded the salts pazufloxacinium mesylate (1), pazufloxacinium mesylate dihydrate (2), pazufloxacinium mesylate hydrate (3) and pazufloxacinium mesylate bis(peroxosolvate) (4), which were all crystallographically characterized. Molecular and crystal structures of these compounds, as well as their thermal behavior, were studied. For all compounds, single-crystal X-ray diffraction confirmed that a proton migrates from methanesulfonic acid to the amino group of pazufloxacin to form a salt. Dehydration of two hydrates occurs as a two-step single-crystal-to-powder process, leading to the formation of two metastable polymorphs of the anhydrous salt. In the solid state, the peroxosolvate compound is stable under ambient conditions for several months, thus making this drug–drug solid suitable for topical application. Full article

Ascorbic Acid (AA), an important biomolecule present in relatively high concentrations in blood and other biological fluids, has been rarely investigated with reference to its effect on the biological mineralization–demineralization processes. To our knowledge, the present work is one of an extremely limited few found in the literature in which the effect of the presence of AA in mineralizing or demineralizing electrolyte solutions is addressed in a quantitative way. We have used the constant saturation method for the accurate measurement of the rates of crystal growth of hydroxyapatite (HAP, Ca₅(PO₄)₃OH), the model compound of the inorganic component of the hard tissues of higher mammals. It was found that both crystal growth and dissolution were accelerated significantly. The increase in crystal growth rates showed stronger dependence on the solution supersaturation (120% increase for the highest and 460% for the lowest) in the presence of 0.1 mM of AA, pH 7.40, 37 °C, 0.15 M NaCl. The dissolution rate increase was less dependent (average of ca. 300% increase). It was concluded from the detailed characterization of the solid that the acceleration effect was due to the uptake of AA on the HAP surface. Full article

In this study, canola oil was used as a natural enriched source of C18 fatty acids and coconut oil as a natural enriched source of C12 fatty acids. The study synthesized five potassium carboxylate (RCOO⁻K⁺) liquid soaps via saponification of coconut–canola oil blends (100:0, 75:25, 50:50, 25:75, 0:100) using a novel in situ dissolution method with controlled KOH addition to prevent solid paste formation. The water demand required to dissolve RCOO⁻K⁺ and mitigate soap crystallization was determined, increasing from 1.76 to 5.18 g H₂O/g oil as canola oil content rose, with soap concentration decreasing from 55.1% (100:0) to 18.5% (0:100). Reaction kinetics revealed faster KOH depletion in coconut oil-rich blends (100:0, 75:25, 50:50; 2 h) compared to canola oil-rich blends (25:75, 0:100; 8 h). Key soap properties, including foam stability, detergency, wettability, viscosity, and thermal behavior, were assessed. The 50:50 blend exhibited the highest foam stability due to the synergistic effects of medium-chain saturated (e.g., laurates) and long-chain unsaturated (e.g., oleates) RCOO⁻K⁺. The short, saturated chains promoted rapid foam formation, while the longer, unsaturated chains enhanced foam film stability. RCOO⁻K⁺ detergency on hair tresses with artificial sebum ranged from 16.9% to 29.7% and was relatively higher compared to sodium lauryl sulfate, sodium laureth sulfate, cocamidopropyl betaine, and sodium cocoyl glutamate (6.1–13.2%) but lower compared to sodium isethionates (34.2%). RCOO⁻K⁺ wettability on cotton textiles improved with higher coconut oil content. RCOO⁻K⁺ contact angles on artificial sebum surface (6.1–13.7°) demonstrated excellent wettability, effectively penetrating and emulsifying hydrophobic residues. Viscosity ranged from 13–45 mPa·s with Newtonian Flow-type behavior. No crystals were observed in the soaps when cooled in the range of 60 to −30 °C. These results demonstrate RCOO⁻K⁺ soaps as tunable, sustainable liquid soaps with performance optimized by adjusting the oil blend ratios. Full article

This study investigates the synthesis of zeolite from kaolinite-rich saprolite from Al-Habala Area, Saudi Arabia, providing insights on kaolinite as an economically viable precursor for zeolite formation. This study was conducted using hydrothermal rectors with a 0.5 M Na₂CO₃ solution at temperatures of 150 °C, 200 °C, and 250 °C over a duration of 336 h. At 150 °C, the dissolution of the clay and feldspar grains began, forming amorphous silica, from which mordenite rods formed. Increased temperatures promoted the formation of cubic analcime crystals at 200 °C to well-developed trapezohedron aggregates at 250 °C. The mineralogical transformations were characterized using SEM, XRD, and ICP-OES analyses, revealing the role of temperature on the morphologies, compositional alteration, and decreasing Na concentrations correlating with the formation of analcime. The newly formed analcime closely matched the composition of natural analcime from different basins. The results confirm that saprolite can effectively serve as a medium for zeolite synthesis, highlighting its potential for cost-effective industrial applications and expanding the understanding of kaolinite-to-zeolite conversion pathways. Full article

Syngenetic fluid inclusions in natural diamonds are indicators of the composition of fluids responsible for growth and crystallization conditions. The chloride concentration in saline fluid inclusions of natural diamonds reaches 50 wt%. We study the dissolution of diamonds in the H₂O-KCl-NaCl system at temperatures of 1200 °C and 1400 °C and a pressure of 5.5 GPa using a BARS high-pressure multi-anvil apparatus. Two scenarios of diamond dissolution were experimentally investigated: (i) metasomatism by saline brines at high oxygen fugacity of the magnetite–hematite buffer; (ii) interaction with reduced carbon-unsaturated water–chloride fluid at low fO₂ imposed by the iron–wüstite buffer. It is found that the presence of alkaline chlorides in the aqueous fluid significantly accelerates diamond dissolution at high oxygen fugacity but inhibits the process under reduced conditions. The morphology of diamond dissolution features is controlled by the presence of water in the fluid over the entire range of the studied P-T-fO₂ conditions. Experimental results indicate that the interaction with oxidizing highly saline fluids during metasomatic events could negatively affect diamond preservation in mantle rocks and eventually lead to the formation of uneconomic kimberlites. Under reducing conditions, water–chloride fluids favor diamond preservation. Full article

Objectives: Transforming poorly soluble crystalline drugs into their amorphous form is a well-established strategy in pharmaceutical science to enhance their solubility and improve their clinical efficacy. However, developing amorphous forms of organic drugs for pharmaceutical applications presents significant technical hurdles due to the lack of suitable analytical tools for the amorphization process. Carbamazepine is a crystalline BCS class II drug commonly used for epilepsy and trigeminal neuralgia, whose clinical efficacy is compromised by its low solubility and slow dissolution. Therefore, this study focuses on investigating the amorphization of carbamazepine to enhance its solubility by using a micro-droplet precipitation system. Methods: These micro-droplets serve as individual reactors, enabling homogeneous nucleation for precipitation of carbamazepine. During crystallization, carbamazepine undergoes an intermediate liquid–liquid phase transition characteristic of two-step nucleation. By varying the solvent’s composition (methanol/water), we characterized the kinetics and stability of the intermediate liquid phase under various conditions. Results: Our results indicate that carbamazepine can undergo either a one-step liquid-to-amorphous-solid phase transition or a two-step liquid-to-crystalline-solid phase transition. Notably, both transitions pass through a liquid-to-dense-liquid phase separation process starting from the supersaturated solution, where the generated intermediate phases exhibit different sizes and numbers that are influenced by the solvent and its concentration. Conclusions: Our findings not only elucidate the mechanism underlying the carbamazepine phase transition but also propose a novel method for studying the amorphous process, which could be broadly applicable to other poorly soluble pharmaceutical compounds and may be helpful to amorphous formulations production, potentially offering significant improvements in drug efficacy and patient compliance. Full article

Rising incidents of critical lithium-ion battery (LIB) accidents highlight the pressing demand for safety enhancements that do not degrade the electrochemical performance parameters. This article provides a comprehensive overview of thermal failure mechanisms and thermal stability strategies, including their cathode, anode, separator, and electrolyte. The analysis covers the current thermal failure mechanisms of each component, including structural changes and boundary reactions, such as Mn dissolution in the cathode, solid–electrolyte interface decomposition in the anode, the melting–shrinkage–perforation of the separator, as well as decomposition–combustion–gas generation in the electrolyte. Furthermore, the article reviews thermal stability improvement methods for each component, including element doping and surface coating of the electrode, high-temperature resistance, flame retardancy, and porosity strategies of the separator, flame retardant, non-flammable solvent, and solid electrolyte strategies of the electrolyte. The findings highlight that incorporating diverse elements into the crystal lattice enhances the thermal stability and extends the service life of electrode materials, while applying surface coatings effectively suppresses the boundary reactions and structural degradation responsible for thermal failure. Furthermore, by using solid electrolytes such as polymer electrolytes, and combining innovative ceramic-polymer composite separators, it is possible to effectively reduce the flammability of these components and enhance their thermal stability. As a result, the overall thermal safety of LIBs is improved. These strategies collectively contribute to the overall thermal safety performance of LIBs. Full article

This study proposed a mechanochemical activation strategy using ethanol-diisopropanolamine (EDIPA) to improve the grindability and hydration reactivity of basic oxygen furnace slag (BOFS), aiming for its large-scale industrial utilization. The incorporation of EDIPA significantly refined the particle size distribution and reduced the repose angle. As a result, the compressive strength of BOFS paste increased by 25.4 MPa at 28 d with only 0.08 wt.% EDIPA. Conductivity tests demonstrated that EDIPA strongly complexes with Ca²⁺, Al³⁺, and Fe³⁺, facilitating the dissolution of active mineral phases, such as C₁₂A₇ and C₂F, and accelerating hydration reactions. XRD and TG analyses confirmed that the incorporation of EDIPA facilitated the formation of Mc (C₄(A,F)ČH₁₁) and increased the content of C-S-H, both of which contributed to microstructural densification. Microstructural observations further revealed that EDIPA refined Ca(OH)₂ crystals, increasing their specific surface area from 4.7 m²/g to 35.2 m²/g. The combined effect of crystal refinement and enhanced hydration product formation resulted in reduced porosity and improved mechanical properties. Overall, the results demonstrated that EDIPA provided an economical, effective, and scalable means of activating BOFS, thereby promoting its high-value utilization in low-carbon construction materials. Full article

The complex system of high-entropy materials makes it challenging to reveal the specific function of each site for oxygen evolution reaction (OER). Here, with nickel foam (NF) as the substrate, FeCoNiCrMo/NF is designed to be prepared by metal–organic frameworks (MOF) as a precursor under an argon atmosphere. XRD analysis confirms that it retains a partial MOF crystal structure (characteristic peak at 2θ = 11.8°) with amorphous carbon (peaks at 22° and 48°). SEM-EDS mapping and XPS demonstrate uniform distribution of Fe, Co, Ni, Cr, and Mo with a molar ratio of 27:24:30:11:9. Electrochemical test results show that FeCoNiCrMo/NF has excellent OER characteristics compared with other reference prepared samples. FeCoNiCrMo/NF has an overpotential of 285 mV at 100 mA cm⁻² and performs continuously for 100 h without significant decline. The OER mechanism of FeCoNiCrMo/NF further reveal that Co and Ni are true active sites, and the dissolution of Cr and Mo promote the conversion of active sites into MOOH following the lattice oxygen mechanism (LOM). The precipitation–dissolution equilibrium of Fe also plays an important role in the OER process. The study of different reaction sites in complex systems points the way to designing efficient and robust catalysts. Full article

This study evaluated and compared two encapsulation techniques—co-crystallization and ionic gelation—for stabilizing bioactive components derived from lavender distillation residues. Utilizing aqueous ethanol extraction (solid residues) and concentration (liquid residues), phenolic-rich extracts were incorporated into encapsulation matrices and processed under controlled conditions. Comprehensive characterization included encapsulation efficiency (Ef), antioxidant activity (AA), moisture content, hygroscopicity, dissolution time, bulk density, and color parameters (L*, a*, b*). Co-crystallization outperformed ionic gelation across most criteria, achieving significantly higher Ef (>150%) and superior functional properties such as lower moisture content (<0.5%), negative hygroscopicity (−6%), and faster dissolution (<60 s). These features suggested enhanced physicochemical stability and suitability for applications requiring long shelf life and rapid solubility. In contrast, extruded beads exhibited high moisture levels (94.0–95.4%) but allowed better control over morphological features. The work introduced a mild-processing approach applied innovatively to the valorization of lavender distillation waste through structurally stable phenolic delivery systems. By systematically benchmarking two distinct encapsulation strategies under equivalent formulation conditions, this study advanced current understanding in bioactive microencapsulation and offers new tools for developing functional ingredients from aromatic plant by-products. Full article

Objectives: Drug-drug cocrystals with improved properties can be used to facilitate the development of synergistic therapeutic combinations. The goal of the present study is to obtain novel drug-drug cocrystals involving two anti-glioma agents, temozolomide (TMZ) and myricetin (MYR). Methods: The novel TMZ-MYR cocrystal was prepared via slurry and solvent evaporation techniques and characterized by X-ray diffraction, thermal analysis, infrared spectroscopy, and dynamic vapor sorption measurements. The stability, compaction, and dissolution properties were also evaluated. Results: Crystal structure analysis revealed that the cocrystal lattice contains two TMZ molecules, one MYR molecule, and four water molecules, which are linked by hydrogen bonding interactions to produce a three-dimensional network. The cocrystal hydrate exhibited favorable stability and tabletability compared to pure TMZ. A dissolution study showed that the maximum solubility of MYR in the cocrystal (176.4 μg/mL) was approximately 6.6 times higher than that of pure MYR·H₂O (26.9 μg/mL), while the solubility of TMZ from the cocrystal (786.7 µg/mL) was remarkably lower than that of pure TMZ (7519.8 µg/mL). The solubility difference between MYR and TMZ was diminished from ~280-fold to ~4.5-fold. Conclusions: Overall, the TMZ-MYR cocrystal optimizes the stability and tabletability of TMZ and the dissolution behavior of both drugs, offering a promising approach for synergistic anti-glioma therapy with improved clinical potential. Full article

Rare earth elements (REEs) have garnered significant global attention due to their essential role in advanced technologies. Sri Lanka is endowed with various REE-bearing minerals, including the apatite-rich deposit in the Eppawala area, commonly known as Eppawala rock phosphate (ERP). However, direct extraction of REEs from ERP is technically challenging and economically unfeasible. This study introduces a novel, integrated approach for recovering REEs from ERP as a by-product of nitrophosphate fertilizer production. The process involves nitric acid-based acidolysis of apatite, optimized at 10 M nitric acid for 2 h at 70 °C with a pulp density of 2.4 mL/g. During cooling crystallization, 42 wt% of calcium was removed as Ca(NO₃)₂.4H₂O while REEs remained in the solution. REEs were then selectively precipitated as REE phosphates via pH-controlled addition of ammonium hydroxide, minimizing the co-precipitation with calcium. Further separation was achieved through selective dissolution in a sulfuric–phosphoric acid mixture, followed by precipitation as sodium rare earth double sulfates. The process achieved over 90% total REE recovery with extraction efficiencies in the order of Pr > Nd > Ce > Gd > Sm > Y > Dy. Samples were characterized for their phase composition, elemental content, and morphology. The fertilizer results confirmed the successful production of a nutrient-rich nitrophosphate (NP) with 18.2% nitrogen and 13.9% phosphorus (as P₂O₅) with a low moisture content (0.6%) and minimal free acid (0.1%), indicating strong agronomic value and storage stability. This study represents one of the pioneering efforts to valorize Sri Lanka’s apatite through a novel, dual-purpose, and circular approach, recovering REEs while simultaneously producing high-quality fertilizer. Full article

Objectives: (1) To compare cytokine levels in participants with serum urate (SU) < 360 µmol/L, SU ≥ 360 µmol/L with and without monosodium urate (MSU) crystal deposition, respectively, and inter-critical gout. (2) To explore the association of IL-1β, IL-6 and high-sensitivity (hs) CRP with disease duration and the frequency of self-reported gout flares. Methods: Samples and data from 184 participants from studies conducted at Academic Rheumatology, Nottingham City Hospital, were included. Serum high-sensitivity CRP and cytokines involved in the pathogenesis of gouty inflammation were measured. MANCOVA and multivariate linear regression were used, as appropriate, and were adjusted for age, sex, body mass index and self-reported comorbidities. p values were adjusted for multiple testing using a 5% false-discovery rate. Results: Participants with inter-critical gout had greater levels of IL-1β (p_corr = 0.009), IL-18 (p_corr = 0.02), IL-6 (p_corr < 0.0001), IP-10 (p_corr < 0.0001), TNF-α (p_corr < 0.0001), GRO-α (p_corr = 0.0006) and hsCRP (p_corr = 0.009) compared to other groups in multivariate analyses and after correcting for multiple testing. There were no differences in cytokine and hsCRP levels in participants with SU < 360 µmol/L and in participants with SU ≥ 360 µmol/L with or without MSU crystal deposition. There was a statistically non-significant trend for association between IL-6 levels and number of self-reported gout flares. Conclusions: Our findings suggest that gout is a chronic inflammatory condition. The pre-clinical phases of gout were not associated with systemic inflammation, potentially due to the modest sample size. Further research is required to understand whether treating gout by targeting the complete dissolution of MSU crystals would reduce systemic inflammation in inter-critical gout. Full article