Search Results (549)

Background. Physicomechanical properties and clinical service of bulk-fill composites depend on their adequate polymerization and depth of cure. Some manufacturers claim that these composites can be adequately cured when used in bulks exceeding 4 mm. Objective. The aim of this study was to compare Vickers microhardness (VMH) and depth of cure (DOC) of six contemporary bulk-fill resin composites at depths of 4 mm and 6 mm. Material and methods. Six bulk-fill composites were evaluated in this study: 1. Tetric EvoCeram Bulk (Ivoclar Vivadent, Schaan, Liechtenstein), (TEC); 2. Filtek Bulk Fill Posterior (3M ESPE Dental Products Division, St. Paul, MN, USA), (FBF); 3. Filtek One Bulk Fill (3M ESPE Dental Products Division, St. Paul, MN, USA, (FOB); 4. SonicFill 2 (Kerr, Orange, CA, USA), (SF2); 5. Admira Fusion X-tra (Voco, GmbH, Cuxhaven, Germany), (AFX); 6. GrandioSO X-tra (Voco, GmbH, Cuxhaven, Germany), (GSX). The 18 specimens (3 of each composite) were prepared in split Teflon moulds of 4 mm diameter and 6 mm thickness. All composites were cured in standard mode for 20 s using LED LCU (D-Light Duo, RF-Pharmaceuticals Sarl, Geneva, Switzerland; 1200–1300 mW/cm). The VMH was measured using a digital Micro Hardness Tester Shimadzu (HMV-2T E, Shimadzu Corporation, Kyoto, Japan). A 50 g (0.5 N) load force was applied for 30 s. Each specimen was measured at five places selected by chance at each level (N = 15). The hardness ratio or DOC was calculated for all samples as the ratio of bottom and surface microhardness at levels of 4 and 6 mm. Data were analysed using one-way ANOVA and Tukey’s post hoc test. Results. Significant reduction in VMH was observed for all tested materials when comparing top surface and bottom (p < 0.01). The highest VMH was obtained for GSX and AFX, and the lowest for TEC. The results show that the degree of polymerization was adequate for all tested materials at a depth of 6 mm, since the hardness ratio exceeded 0.80 in all cases. The hardness ratio at 4 mm was high for all tested composites ranging from 0.91 for TEC to 0.98 for GSX. All composites showed adequate DOC at the bottom of the 6 mm bulk samples. However, the hardness ratio was the highest for Admira Fusion X-tra (0.96) and GrandioSO X-tra (0.97). Conclusions. All tested materials showed a significant decrease in microhardness from the top surface to the bottom. The DOC was adequate for all bulk-fill composites at a depth of 6 mm cured under standard mode for 20 s. All bulk-fill resin composites evaluated in this study can be used in bulk, up to 6 mm. Full article

The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage—they eliminate the need for physical samples and laboratory facilities, while providing rapid and cost-effective alternatives to expensive and time-consuming experimental testing. Computational methods can often effectively address common challenges associated with natural compounds, such as chemical instability and poor solubility. Through a review of the relevant scientific literature, we present a comprehensive analysis of in silico methods and tools used for ADME prediction, specifically examining their application to natural compounds. Whereas we focus on identifying the predominant computational approaches applicable to natural compounds, these tools were developed for conventional drug discovery and are of general use. We examine an array of computational approaches for evaluating natural compounds, including fundamental methods like quantum mechanics calculations, molecular docking, and pharmacophore modeling, as well as more complex techniques such as QSAR analysis, molecular dynamics simulations, and PBPK modeling. Full article

Fibrate pharmaceuticals (fibrates), as a widespread class of emerging contaminants, pose potential risks to both ecological systems and human health. The photocatalytic system based on nitrogen (N) and fluorine (F) co-doped TiO₂ nanotube arrays (NF-TNAs) provides a renewable solution for fibrate pharmaceutical removal from water, powered by inexhaustible sunlight. In this study, the degradation of two typical fibrates, i.e., bezafibrate (BZF) and ciprofibrate (CPF), under simulated sunlight irradiation through NF-TNAs were investigated. The photocatalytic degradation of BZF/CPF was achieved through combined radical and non-radical oxidation processes, while the generation and reaction mechanisms of associated reactive oxygen species (ROS) were examined. Electron paramagnetic resonance detection and quenching tests confirmed the existence of h⁺, •OH, O₂^•−, and ¹O₂, with O₂^•− playing the predominant role. The transformation products (TPs) of BZF/CPF were identified through high-resolution mass spectrometry analysis combined with quantum chemical calculations to elucidate the degradation pathways. The influence of co-existing ions and typical natural organic matters (NOM) on BZF/CPF degradation were also tested. Eventually, the ecological risk of BZF/CPF transformation products was assessed through quantitative structure–activity relationship (QSAR) modeling, and the results showed that the proposed photocatalytic system can largely alleviate fibrate toxicity. Full article

Accurate and efficient estimation of microalgae cell concentration is critical for applications in hydrochemical monitoring, biofuel production, pharmaceuticals, and ecological studies. Traditional methods, such as manual counting with a hemocytometer, are time-consuming and prone to human error, while automated systems are often costly and require extensive training data. This paper presents a low-cost, automated approach for estimating cell concentration in Chlorella vulgaris suspensions using classical computer vision techniques. The proposed method eliminates the need for deep learning by leveraging the Hough circle transform to detect and count cells in microscope images, combined with a conversion factor to translate pixel measurements into metric units for direct concentration calculation (cells/mL). Validation against manual hemocytometer counts demonstrated strong agreement, with a Pearson correlation coefficient of 0.96 and a mean percentage difference of 17.96%. The system achieves rapid processing (under 30 s per image) and offers interpretability, allowing specialists to verify results visually. Key advantages include affordability, minimal hardware requirements, and adaptability to other microbiological applications. Limitations, such as sensitivity to cell clumping and impurities, are discussed. This work provides a practical, accessible solution for laboratories lacking expensive automated equipment, bridging the gap between manual methods and high-end technologies. Full article

Background: Transition metal complexes incorporating fluorinated counter anions represent a significant class of compounds with broad applications in industry, pharmaceuticals, and biomedicine. These fluorinated anions are known to enhance the solubility, stability, and reactivity of the complexes, thereby expanding their functional utility in various chemical and biological contexts. Methods: A set of metal(II) complexes of the general formula [MPy₆][B(C₆F₅)₄]₂ where (Py = pyridine, M = Mn (1), Fe (2), Co (3), Ni (4), Cu (5), Zn (6)) have been synthesized by direct reaction of metal halides and pyridine in the presence of Ag[B(C₆F₅)₄]. The complexes were characterized using different techniques to assure their purity, such as elemental analysis (EA), electron paramagnetic resonance (EPR) spectroscopy, thermogravimetric analysis (TGA), ultraviolet–visible (UV–Vis) spectroscopy, ¹¹B-NMR, ¹H-NMR, and FT-IR spectroscopy. The antimicrobial and antifungal properties against different types of bacteria and fungi were studied for all prepared complexes. Results: The synthesized complexes exhibited broad-spectrum antimicrobial activity, demonstrating variable efficacy compared to the reference antibiotic, oxytetracycline (positive control). Notably, complex 6 displayed exceptional antibacterial activity against Streptococcus pyogenes, with a minimum inhibitory concentration (MIC) of 4 µg/mL, outperforming the control (MIC = 8 µg/mL). Complexes 1, 2, and 4 showed promising activity against Shigella flexneri, Klebsiella pneumoniae, and Streptococcus pyogenes, each with MIC values of 8 µg/mL. Conversely, the lowest activity (MIC = 512 µg/mL) was observed for complexes 3, 5, and 6 against Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, respectively. Regarding antifungal properties, complexes 5 and 6 demonstrated the highest activity against Candida albicans, with MIC values of 8 µg/mL, equivalent to that of the positive control, fluconazole. Density functional theory (DFT) calculations confirmed an overall octahedral coordination geometry for all complexes, with tetragonal distortions identified in complexes 3, 4, and 5. Full article

Background/Objectives: This study aims to present a strategic approach to enhancing the photostability and antioxidative resilience of curcumin and capsaicin by integrating selected natural stabilizers within a nanoemulsion-based delivery system. Methods: Coffee extract (Coffea arabica Linn.), along with its active components and vitamin E-containing natural oils, was assessed in terms of improving the photostabilizing and antioxidative retention abilities of curcumin and capsaicin. An optimized ratio of the active mixture was then loaded into a nanoformulation. Results: The analysis of active contents with validated high-performance liquid chromatography (HPLC), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays confirmed the stabilization enhancement after irradiation with UV and white light for 72,000–84,000 lux hours. The optimized combination of coffee extract with turmeric and chili mixtures loaded into the optimized nanoemulsion enhanced the half-lives (T_1/2) of curcumin and capsaicin by 416% and 390%, respectively. The interactions of curcumin and capsaicin with caffeine and chlorogenic acid were elucidated using computational calculations. Interaction energies (E_int), HOMO-LUMO energy gap (HLG) analysis, and global reactivity descriptors revealed hydrogen bonding interactions be-tween capsaicin and chlorogenic acid, as well as between curcumin and caffeine. Conclusions: By leveraging the synergistic antioxidative properties of coffee extract and vitamin E within a nanoemulsion matrix, this study overcomes the intrinsic stability limitations of curcumin and capsaicin, offering a robust platform for future pharmaceutical and nutraceutical applications. Full article

Background/Objectives: The oral cavity represents a convenient route of administration for drugs that exhibit significant hepatic first-pass extraction. In this study, the mucosal permeation properties of selected active pharmaceutical ingredients (APIs) incorporated into oral cavity drug products that are approved by the U.S. Food and Drug Administration were quantified using the human-derived sublingual HO-1-u-1 and buccal EpiOral™ in vitro tissue models. Methods: Epithelial barrier properties were monitored using propranolol and Lucifer Yellow as prototypic transcellular and paracellular markers. APIs were dissolved in artificial saliva, pH 6.7, and transepithelial flux from the apical to the basolateral compartment was quantified using HPLC. Results: Apparent permeability coefficients (Papp) calculated for these APIs in the sublingual HO-1-u-1 tissue model varied from Papp = 2.72 ± 0.06 × 10⁻⁵ cm/s for asenapine to Papp = 6.21 ± 2.60 × 10⁻⁵ cm/s for naloxone. In contrast, the buccal EpiOral™ tissue model demonstrated greater discrimination power in terms of permeation properties for the same APIs, with values ranging from Papp = 3.31 ± 0.83 × 10⁻⁷ cm/s for acyclovir to Papp = 2.56 ± 0.68 × 10⁻⁵ cm/s for sufentanil. The tissue-associated dose fraction recovered at the end of the transport experiment was significantly increased in the buccal EpiOral™ tissue model, reaching up to 8.5% for sufentanil. Conclusions: Experimental permeation data collected for selected APIs in FDA-approved oral cavity products will serve as a training set to aid the development of predictive computational models for improving algorithms that describe drug absorption from the oral cavity. Following a robust in vitro–in vivo correlation analysis, it is expected that such innovative in silico modeling strategies will the accelerate development of generic oral cavity products by facilitating the utility of model-integrated evidence to support decision making in generic drug development and regulatory approval. Full article

In recent years, microalgae have gained significant biotechnological importance as a sustainable source of various metabolites of industrial interest. Among these, paramylon, a polysaccharide produced by the microalga Euglena gracilis, stands out for its diverse applications in biomedicine and pharmaceuticals. E. gracilis is an adaptable secondary eukaryote capable of growing photoautotrophically, heterotrophically and mixotrophically. During photoautotrophic growth, varying light conditions impact biomass and paramylon production. To investigate the effects of varying illumination more thoroughly, we designed and built a modular photobioreactor that allowed us to simultaneously evaluate the photoautotrophic growth of E. gracilis under twelve different light conditions: seven single-spectrum lights (ultraviolet, royal blue, blue, green, red, far-red, and infrared) and five composite-spectrum lights (3000 K, 10,000 K, and 30,000 K white lights, amber light, and “Full-spectrum” light). The 24-day growing kinetics were recorded, and the growth parameters were calculated for each light regime. Both growth curves and pigment composition present differences attributable to the light regime used for cell culture. Additionally, photosynthetic and respiratory machinery functionality were proven by oximetry. Finally, our results strongly suggest that the far-red component enhances paramylon production during the stationary phase. Full article

White mulberry (Morus alba L.) is a tree growing up to 15 m in height. It is a plant whose cultivation is historically associated with silk production. Mulberry leaves are the only food source of the mulberry silkworm caterpillars (Bombyx mori L.). The cultivation of this tree has recently gained renewed importance. Due to the content of numerous bioactive substances, mulberry is a valuable raw material for the food, pharmaceutical and herbal industries. This article presents the results of tests on pellets from 1-, 3- and 5-year-old branches, which are waste biomass remaining after pruning mulberry shrubs cultivated to obtain leaves to feed silkworms. Additionally, analyses of pellets from mulberry leaves were also carried out. For the specified mulberry biomass yield, analyses of chemical composition of mulberry biomass (branches and leaves) were carried out, and energy properties (heat of combustion and calorific value) and energy potential were calculated. The heat of combustion of pellet from mulberry branches was, on average, 19,266 MJ∙Mg⁻¹, and the calorific value was 17,726 MJ∙Mg⁻¹. The energy potential, on the other hand, was, on average, 159 GJ∙ha⁻¹ and 44 MWh∙ha⁻¹. The obtained results indicate the possibility of the effective use of mulberry branches after the annual pruning of bushes in plantations for energy purposes. Full article

Background: The solubility and phase behavior of APIs are crucial for the development of medicines and ensuring their stability. However, conventional experimental approaches often do not allow for the precise determination of phase transitions and solubility limits, especially for poorly soluble compounds. Purpose: The aim of this study was to demonstrate the possibility of using the laser microinterferometry method, traditionally used to define the phase equilibria of polymer systems, to determine the thermodynamic solubility of the APIs. Methods: Using laser microinterferometry, the thermodynamic solubility and phase behavior of amorphous darunavir were determined in various pharmaceutical solvents, including vaseline and olive oils, water, glycerol, alcohols (methanol, ethanol, isopropanol), glycols (propylene glycol, polyethylene glycol 400, polypropylene glycol 425, polyethylene glycol 4000), and ethoxylated polyethylene glycol ether obtained from castor oil in the temperature range of 25–130 °C. Dissolution kinetics was estimated at 25 °C. Hansen solubility parameter calculations were also performed for comparison. Results: Darunavir is practically insoluble in olive and vaseline oils. In water and glycerol, an amorphous equilibrium with an upper critical solution temperature was observed, and phase diagrams were constructed for the first time. In alcohols, glycols, and ethoxylated polyethylene glycol ether obtained from castor oil, darunavir showed high solubility, accompanied by the formation of crystalline solvates. Kinetic evaluation showed that the dissolution rate of darunavir in methanol is four times faster than in ethanol and thirty times faster than in isopropanol. Comparison of the obtained data with previously published and calculated values of solubility parameters demonstrates a good correlation. Conclusions: Laser microinterferometry has been demonstrated as a potential tool for determining the thermodynamic solubility of APIs. This method allows for directly observing the dissolution process, determining the solubility limits, and detecting phase transitions. These studies are necessary for selecting appropriate excipients, preventing the formation of undesirable solvates and predicting formulation stability, which are all critical factors in early-stage drug development and pharmaceutical formulation design. Full article

A series of new isatin hydrazones bearing phosphorus-containing moiety was synthesized through a simple, high-yield and easy work-up reaction of phosphine oxide (Phosenazide) or phosphinate (2-chloroethyl (4-(dimethylamino)phenyl)(2-hydrazinyl-2-oxoethyl)phosphinate, CAPAH) hydrazides with aryl-substituted isatins. The ³¹P NMR technique showed that, in most cases, out of 12 examples in solution, the ratio of the two spatial isomers varied from 1:1 to 1:3. Quantum chemical calculations confirmed the predominance of Z,syn form both in the gas phase and in solution. According to X-ray analysis data in crystals, they exist only in Z,syn form too. Most of the phosphine oxide derivatives and 5-methoxy- and 5-bromoaryl phosphinate analogs exhibit anti-aggregant activity at the level of acetylsalicylic acid but inhibit platelet activation processes more effectively. The 5-chloro type phosphinate derivative exhibits anti-aggregant properties more effectively than acetylsalicylic acid under the conditions of the tissue factor (TF)-activated thromboelastography (TEG) model, the ex vivo thrombosis model. Thus, all the obtained results can become the basis for future pharmaceutical developments to create effective anti-aggregation drugs with broad antithrombotic potential. Full article

Thermokinetic characterization of amorphous carbamazepine was performed utilizing non-isothermal differential scanning calorimetry (DSC) and thermogravimetry (TGA). Structural relaxation of the amorphous matrix was described in terms of the Tool–Narayanaswamy–Moynihan model with the following parameters: Δh* ≈ 200–300 kJ·mol⁻¹, β = 0.57, x = 0.44. The crystallization of the amorphous phase was modeled using complex Šesták–Berggren kinetics, which incorporates temperature-dependent activation energy and degree of autocatalysis. The activation energy of the crystal growth was determined to be >320 kJ·mol⁻¹ at the glass transition temperature (T_g). Owing to such a high value, the amorphous carbamazepine is stable at T_g, allowing for extensive processing of the amorphous phase (e.g., self-healing of the quench-induced mechanical defects or internal stress). A discussion was conducted regarding the converse relation between the activation energies of relaxation and crystal growth, which is possibly responsible for the absence of sub-T_g crystal growth modes. The high-temperature thermal decomposition of carbamazepine proceeds via multistep kinetics, identically in both an inert and an oxidizing atmosphere. A complex reaction mechanism, consisting of a series of consecutive and competing reactions, was proposed to explain the second decomposition step, which exhibited a temporary mass increase. Whereas a negligible degree of carbamazepine degradation was predicted for the temperature characteristic of the pharmaceutical hot-melt extrusion (~150 °C), the degradation risk during the pharmaceutical 3D printing was calculated to be considerably higher (1–2% mass loss at temperatures 190–200 °C). Full article

The current paper examines the sustainable possibility for recycling unused or expired Metoprolol (MET), a benzodiazepine derivative, as an effective corrosion inhibitor for carbon steel in saline solutions. Repurposing expired medicinal drugs aligns with green chemistry concepts and supports circular economy initiatives by reducing pharmaceutical waste and averting the production of new synthetic inhibitors. The technical benefit of recycling expired MET drugs pertains to the elimination of costs associated with organic inhibitor manufacturing and the decrease in disposal expenses for the expired medication. A combination of electrochemical techniques (potentiodynamic polarization and electrochemical impedance spectroscopy) and quantum chemical calculations was employed to evaluate the inhibitory mechanism and efficacy of MET. At a concentration of 10⁻³ M, MET reduced the corrosion current density from 19.38 to 5.97 μA cm⁻², achieving a maximum IE of 69.1%. Adsorption Gibbs free energy, determined using different adsorption isotherms, revealed that interactions between metal atoms and MET adsorbed molecules have a chemical character with a ∆G^o_ads value of −50.7 kJ·mol⁻¹. Furthermore, quantum chemistry calculations indicate that the investigated drug, owing to its molecular structure (E_HOMO = −9.12 eV, E_LUMO = 0.21 eV, µ = 3.95 D), possesses the capacity to establish an adsorption layer on the metal surface, thereby impeding the diffusion of molecules and ions involved in the overall corrosion process. The results obtained using the different techniques were in good agreement and highlighted the effectiveness of MET in the corrosion inhibition of carbon steel. Full article

Background: Solubility is a fundamental physicochemical property in pharmaceutical, chemical and environmental industrial processes. Regarding Triclocarban (TCC), a broad-spectrum antimicrobial, solubility is particularly challenging due to its low aqueous solubility and hydrophobic nature; these challenges can be addressed by some effective techniques such as cosolvency, which allows one to increase the solubility of drugs by several orders of magnitude. This study aims to thermodynamically evaluate the solubility of TCC in cosolvent mixtures of PEG 200 + water at different temperatures. Methods: Experimental solubility data were determined using the shake-flask followed by UV quantification analysis at saturation methods, and thermodynamic functions of the solution processes were calculated using the Gibbs–van’t Hoff–Krug model. Results: The solubility results demonstrate the positive cosolvent effect of PEG 200 on the solubility of TCC, whose solution process is thermodynamically strongly governed by the enthalpy of solution with entropic preference in PEG 200-rich mixtures. Conclusions: The solubility of TCC is an endothermic, thermo-dependent process. The addition of PEG 200 to the cosolvent mixture favors this process and shows a positive cosolvent effect. Full article

Polymethyl methacrylate (PMMA) is a polymer with excellent properties for water remediation. Understanding the molecular interactions between pharmaceuticals, such as β-blockers, and PMMA is essential for optimizing purification technologies. Atomistic calculations provide a detailed understanding of the interaction between molecules without the need for expensive equipment. This study presents a computational analysis of how PMMA interacts with salbutamol and atenolol. Geometrical optimizations were performed using semiempirical and density functional theory (DFT) calculations. To identify interactions between PMMA and pharmaceuticals, we employed the reduced density gradient (RDG) approach, providing insight into intramolecular noncovalent interactions between PMMA’s atoms and pharmaceuticals. Full article