Search Results (6,641)

This paper proposes a genetic algorithm (GA) for the Dual-Resource Flexible Job Shop Scheduling Problem with Partial Resource Allocation (DRFJSSP-PRA), a particular variant of a dual-resource constrained scheduling problem that has not been fully explored due to its intricate nature. The DRFJSSP-PRA poses a challenging scheduling problem, having several applications in many industries, including food, chemistry and pharmaceutics. The proposed algorithm is applied to real-world scheduling instances in pharmaceutical quality control. The objective function considered is the total completion time. The GA is compared with three state-of-the-art algorithms. For small- and medium-size instances, the proposed algorithm achieves optimal or near optimal results for the majority of the instances tested. For large-sized instances, the proposed GA outperforms all the other algorithms, in all of the tested instances. Thus, the experimental results show that the proposed GA achieves competitive results for any type of instance. The proposed algorithm also has the ability to optimize production processes through scheduling, leading to potential cost savings, increased efficiency, and improved competitiveness. Full article

Resveratrol (RSV) is a poorly water-soluble polyphenolic compound with various potential health benefits, but its pharmaceutical application is limited by low aqueous solubility and poor oral bioavailability. Additive manufacturing (AM), particularly fused deposition modeling (FDM) 3D printing, offers a flexible approach for fabricating oral dosage forms with customized geometry and internal architecture. In this study, hot-melt extrusion (HME) combined with fused deposition modeling (FDM) 3D printing was used to prepare RSV-loaded tablets with different infill patterns. Hydroxypropyl methylcellulose acetate succinate and hydroxypropyl cellulose were selected as polymeric carriers to prepare RSV-loaded filaments suitable for FDM printing. The effects of infill pattern on the solid-state characteristics, dimensional accuracy, mechanical properties, floating behavior, and in vitro drug release of the printed tablets were systematically investigated. Differential scanning calorimetry, powder X-ray diffraction, and polarized light microscopy indicated that RSV was mainly converted into an amorphous or molecularly dispersed state after HME and FDM processing. All designed tablets were successfully printed and showed acceptable shape fidelity, while different infill patterns resulted in variations in tablet weight, mechanical strength, floating duration, and release behavior. In vitro dissolution studies showed that the RSV release profiles were dependent on the internal infill architecture. Tablets with more complex infill patterns generally exhibited slower drug release, which may be related to differences in internal pore structure, medium penetration pathways, matrix hydration, and diffusion distance. Release kinetic analysis further suggested that RSV release from the printed tablets involved a combination of diffusion and polymer relaxation processes. These results demonstrate that infill pattern is an important structural parameter for modulating the mechanical performance and drug release behavior of FDM 3D-printed RSV tablets. This study provides useful guidance for the design of 3D-printed oral dosage forms with tunable release characteristics. Full article

This review examines the emerging role of machine learning (ML) in pharmaceutical chemistry, with emphasis on molecular design, synthetic feasibility, and structure–property–performance (SPP) relationships. By enabling pre-synthesis prediction of physicochemical properties, reaction pathways, and pharmaceutical performance, ML can reduce empirical trial-and-error experimentation and support more efficient exploration of chemical space. A structured narrative review design with PRISMA-aligned systematic search elements was used to evaluate 101 studies, enabling transparent literature identification, eligibility screening, and thematic synthesis across heterogeneous ML applications in pharmaceutical chemistry. This review examines structure–property relationships (SPRs) and property–performance relationships (PPRs), with emphasis on key pharmaceutical endpoints such as solubility, permeability, stability, dissolution, and bioavailability. An integrated SPP framework is proposed to connect molecular structure, intermediate properties, and final performance outcomes while incorporating retrosynthetic analysis and experimental feedback and closed-loop optimization. Recent frontier developments are also discussed, including molecular foundation models, multimodal language–graph models, diffusion-based molecular generation, E(3)-equivariant models, and MolMIM-like latent-space optimization. This review also covers co-folding and joint ligand–protein modeling, Boltz-2-like affinity prediction, AlphaFold 3-related biomolecular interaction modeling, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. Key limitations include dataset leakage, benchmark inconsistency, assay variability, conformational and protonation-state effects, reproducibility challenges, regulatory constraints, and the gap between computational prediction and prospective experimental validation. Future progress is expected to depend on hybrid physics–ML models, uncertainty-aware prospective validation, autonomous experimentation, explainable artificial intelligence, and sustainability-aware molecular design. Overall, ML is evolving from a predictive tool into a chemically informed decision-support framework for rational, synthesis-aware, and experimentally validated pharmaceutical development. Full article

Cyclodextrin glycosyltransferase (CGTase) is a highly valuable biocatalyst in industrial starch conversion, particularly for the synthesis of cyclic oligosaccharides. In this study, a CGTase, designated HfCGT, was cloned from Haloferax sp. and heterologously expressed in Escherichia coli. The recombinant enzyme was purified and biochemically characterized. HfCGT exhibited maximal catalytic activity at 70 °C and pH 8.0, tolerance to metal ions and EDTA, and enhanced activity in the presence of 1 M NaCl and Ca²⁺. High-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) analyses revealed that the starch products by HfCGT degradation were mainly large-ring cyclodextrins (LR-CDs) with polymerization degrees of 9 to 20. Altogether, the thermostability, haloalkaliphilic, and distinctive product profile make HfCGT a promising biocatalyst for pharmaceutical, food, and biotechnological applications. Full article

Background: Recent technology improvements have enabled desorption electrospray ionisation (DESI) mass spectrometry imaging to achieve down to 5 µm (pixel) image resolution. However, operating at this resolution introduces challenges, particularly regarding increased total analysis time and the need for sufficient instrument sensitivity to detect analytes from very small tissue areas. Methods: High mass and image resolution DESI imaging was performed on rat brain tissue using a Xevo™ MRT benchtop mass spectrometer equipped with a multi-reflecting time-of-flight mass analyser and a DESI XS source. Data acquisition was conducted at speeds of up to 100 Hz. Sensitivity was assessed using a dilution series of five Active Pharmaceutical Ingredients (APIs) spotted onto porcine liver tissue. Signal detection limits were evaluated using extracted ion chromatograms (XICs) with signal-to-noise (S/N) calculations against blank samples. Additionally, enhanced duty cycle (EDC) was applied to evaluate improvements in analyte signal intensity across specific mass ranges in both positive and negative ionisation modes. Results: At acquisition speeds of up to 100 Hz, excellent data quality was achieved, with signal intensity remaining suitable for analytical applications. All five tested APIs were detectable at concentrations of 25 pg/mm². Three of the five compounds were further detected at concentrations as low as 2.5 pg/mm², with signal-to-noise ratios greater than 5. The application of EDC resulted in a significant increase in analyte signal intensity within the targeted mass ranges, particularly for small molecule endogenous metabolites and lipids, in both ionisation modes. Furthermore, the system demonstrated substantially improved spectral quality, achieving mass resolution up to 100,000 FWHM. This enabled the resolution of previously indistinguishable analytes with significantly improved mass accuracy compared to systems operating at approximately 30,000 FWHM. Conclusions: The Xevo™ MRT mass spectrometer with DESI XS source enables high-resolution DESI imaging at speeds up to 100 Hz without compromising data quality or sensitivity. The system demonstrates excellent detection limits for pharmaceutical compounds and improved performance through enhanced duty cycle operation. Overall, the combination of high spatial resolution, increased mass resolution, and improved spectral quality allows for more accurate analyte differentiation, representing a significant advancement over lower-resolution systems. Full article

Recent advancements in computer vision, particularly in detection, segmentation, and classification, have significantly impacted various domains. However, these advancements are still strongly tied to RGB-based systems, which are insufficient for applications in industries such as waste sorting, pharmaceuticals, and defence, where material characterization beyond shape or visible colour is necessary. Hyperspectral (HS) imaging captures spatial and spectral information for each pixel and therefore offers a promising route for material-level classification. This study evaluates the potential of combining HS imaging with deep learning for plastic material classification. The work includes: (i) the design of an experimental setup with a HS line-scan camera, conveyor, and controlled illumination; (ii) the construction of an object-disjoint dataset of HDPE, PET, PP, and PS samples with semi-automated mask generation and Raman spectroscopy-based labelling; and (iii) the development of P1CH, a lightweight pixel-wise 1D convolutional hyperspectral classifier. On object-disjoint test images, P1CH achieved 97.44% all-pixel accuracy. A boundary sensitivity analysis, reported separately because semi-automated labels are uncertain at material/background interfaces, yielded 99.94% accuracy after excluding a pre-defined two-pixel border band. Additional ablation, baseline, and robustness analyses show that the proposed pixel-wise spectral approach is effective for small fragments, visually similar plastics, and overlapping materials, while black or very dark plastics remain challenging under the present camera and illumination configuration. Full article

This review aims to compare the biological properties of eleven fruits of the Prunus species, with the focus on their potential in the prevention and management of chronic diseases. The search spanned publications from 2000 to May 2026, only in English, and utilized databases such as PubMed, Web of Science, and Google Scholar, focusing on the in vitro and in vivo studies. The exclusion criteria included review articles, studies focusing exclusively on isolated phytochemicals or synthetic derivatives from Prunus species, and in silico or theoretical analyses. The fruits of Prunus species exhibited a broad spectrum of activities, including antioxidant, anti-inflammatory, anticancer, antihyperglycemic, or neuroprotective. Interestingly, sour cherries exhibited sleep-enhancing, and xanthine oxidase-inhibitory effects, while apricots showed promising hepatoprotective activity. Key species, including apricots, cherries, peaches, and plums, are widely recognized for their bioactive phytochemicals and potential health benefits, while some (e.g., bird cherry, blackthorn) are less examined, although promising. Prunus fruits revealed health-benefit potential, that at least partially supports their ethnopharmacological uses. However, further clinical and mechanistic studies are warranted to validate their efficacy and explore potential applications in pharmaceutical formulations. Full article

Background: 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a postbiotic gut microbiota-derived flavanol metabolite with reported anti-inflammatory activity. Despite growing interest in its potential dermatological applications, its pharmaceutical properties and suitability for topical delivery have not been systematically investigated. This study aimed to perform the first comprehensive preformulation and formulation-oriented evaluation of DHPV and to develop stable topical ointment formulations suitable for further dermatological research. Methods: The physicochemical properties of DHPV were characterized using powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), quantitative solubility assessment, and excipient compatibility studies. Based on the obtained preformulation data, two anhydrous ointment formulations containing DHPV were developed. The formulations were evaluated for homogeneity, rheological behavior, chemical stability under accelerated storage conditions, and in vitro drug release performance. Results: DHPV was identified as a crystalline compound with heterogeneous particle morphology and limited aqueous solubility. Quantitative solubility studies demonstrated the highest solubility in PEG 300 and glycol-based solvents. Compatibility testing revealed increased impurity formation in hydrophilic environments, whereas lipophilic excipients provided improved chemical stability. Both ointment formulations exhibited acceptable physical characteristics and maintained DHPV stability throughout accelerated storage. However, marked differences in release behavior were observed. The lipid–wax formulation showed significantly higher release rates, lower variability, and more reproducible release profiles than the petrolatum-based reference formulation, indicating more efficient diffusion of DHPV from the semisolid matrix. Conclusions: The physicochemical characteristics of DHPV strongly influence formulation design and performance. Anhydrous lipid-based systems provide a favorable environment for maintaining DHPV stability, while formulation composition significantly affects drug release. The developed lipid–wax formulation represents a promising platform for future skin permeation, pharmacodynamic, and efficacy studies. Full article

Rice bran polysaccharides (RBPs) are natural plant-derived polysaccharides predominantly found in the rice bran layer, a major byproduct of rice milling, and exhibit a wide range of biological activities. These bioactive components, with their complex structures and diverse functions, hold immense potential for application in the food, pharmaceutical, and cosmetic industries. This review summarizes recent advances in the composition and bioactive functions of RBPs, with particular emphasis on how extraction methods and physicochemical modifications alter their molecular weight, monosaccharide composition, and chain conformation, thereby modulating key biological activities, including anti-inflammatory, antioxidant, immunomodulatory, and gut microbiota-regulating effects. Furthermore, to better elucidate their potential in industrial applications, this study systematically analyzes how the physicochemical properties of rice bran polysaccharides influence production and processing, with particular attention to their emerging roles as delivery carriers, food additives, and bioactive components. Full article

Human urine is a sustainable source of nutrients with significant fertilizer potential. The presence of pharmaceutical residues, however, obstructs its use in agriculture. Also, the loss of ammonia formed in enzyme-catalyzed hydrolysis of urea in stored urine compromises the approach. This study presents gas-phase pulsed corona discharge (PCD) used in the oxidation of pharmaceuticals and enzymes, improving the applicability of urine as a fertilizer. The prioritized beta-blocker propranolol (PR) and antibiotic tetracycline were chosen as target micropollutants for the experimental study, demonstrating enhanced oxidation relative to matrix constituents. Tetracycline showed its more recalcitrant character in urine than PR for its more pronounced matrix-mediated scavenging or complexation. The PCD oxidation significantly lowered the urease enzyme activity, thus preventing nitrogen loss through ammonia volatilization. According to the phytotoxicity assessment using the Pisum sativum garden peas test, urine PCD-treated with the energy dose sufficient to substantially degrade pharmaceuticals is not phytotoxic when applied at recommended agronomic doses. The findings reveal the use of PCD as an energy-efficient technology for producing safe and stable urine-derived fertilizer. Full article

Agri-food byproducts are increasingly recognized as sustainable feedstocks for high-value bioactive compounds; but their practical valorization requires integrated evidence on recovery conditions; chemical composition; bioactivity; and application readiness. This review critically examines green recovery strategies and chemical profiling platforms for bioactive compounds recovered from peels; pomace; seed residues; hulls; vegetation waters; and pruning waste. Emphasis is placed on how extraction variables shape chemical profiles; extract quality; and reported biological activities. Ultrasound- and microwave-assisted extraction; enzyme- and fermentation-assisted recovery; supercritical fluid extraction; pressurized liquid extraction; pulsed electric field-assisted pretreatment; and green solvent-based extraction are discussed in terms of target-compound selectivity; solvent and energy demand; process safety; scalability; and sustainability-related evidence. Chromatographic; mass-spectrometric; spectroscopic; and metabolomics-based profiling approaches are evaluated for identification; annotation; quantification; fingerprinting; quality-marker selection; and standardization; with confidence levels distinguished according to authentic-standard matching; tandem mass spectrometry evidence; spectral libraries; or fingerprint-level evidence. Circular valorization pathways in food; nutraceutical; cosmetic; pharmaceutical, and biopesticide-related applications are further considered with attention to feedstock heterogeneity; process standardization; stability; safety; regulatory feasibility; scalability; and techno-economic feasibility. Overall; this review provides a linkage-oriented framework for developing standardized; application-readiness-oriented bioactive candidates from agri-food byproducts. Full article

Compounds from olive (Olea europaea L.) and pomegranate (Punica granatum L.) have many beneficial effects on human health. This review paper considers the inhibitory potential, under in vitro conditions, of bioactive components of olive and pomegranate on different enzyme systems. Research shows that olive polyphenols (oleuropein, hydroxytyrosol, luteolin, and oleocanthal), as well as pomegranate polyphenols (punicalagin, urolithin A, ellagic acid), inhibit cyclooxygenase and lipoxygenase enzymes, which are associated with inflammatory processes. They also show an inhibitory effect on acetylcholinesterase, butyrylcholinesterase, and β-secretase, which opens up the possibility of a strong neuroprotective effect. Olive and pomegranate polyphenols also have an inhibitory effect on enzymes involved in carbohydrate metabolism, such as amylase and glucosidase, and can help fight diabetes and regulate human metabolism. In addition, polyphenols and extracts of both plants showed an inhibitory effect on cytochrome P450 enzymes, which metabolize most drugs. These data open up the possibility of interactions with certain groups of drugs. The current evidence supports the view that olive and pomegranate polyphenols act as biologically versatile compounds with considerable pharmaceutical and nutraceutical potential. Future investigations integrating enzymology, metabolomics, molecular docking, and clinical validation will be essential for translating these promising in vitro findings into evidence-based therapeutic applications. Full article

Volatile fatty acids (VFAs) are essential precursors in chemical synthesis for various chemicals, polymers, pharmaceuticals, and fragrance compounds. Acidogenic anaerobic digestion (or arrested methanogenesis) is a promising method to stabilize organic wastes and convert them to value-added products such as VFAs. However, the VFAs’ accumulation could in turn suppress the fermentation process through product inhibition and limit the titer of VFA in the digestate. Therefore, in situ separation and recovery of VFAs from the fermentate is crucial to constructing an effective continuous VFA-producing system. Recent research has been dedicated to addressing these issues and advancing the utilization of biobased VFAs, particularly through process-intensified strategies employing novel green solvents such as natural deep eutectic solvents. Furthermore, in situ conversion of VFAs into esters is another potential strategy for VFA removal. However, VFA esterification in an aqueous medium is challenging due to the abundant water driving the reaction toward hydrolysis. Recent advances in free or immobilized enzyme catalysis in solvents have demonstrated improved ester yield by providing a hydrophobic space for the esterification reaction in aqueous solution. In this review, we present an overview of critical aspects on the state-of-the-art of green solvent-based process intensification strategies, including feedstock selection and pretreatment, operating condition optimization, advances in membrane- and solvent-based recovery methods, and biocatalytic in situ esterification. Lastly, we provide perspectives toward cost-effective, continuous, high-solid, environmental-benign, and industrial-relevant VFA production applications. Full article

Caryocar coriaceum Wittm. (Caryocaraceae) is a native Brazilian species predominantly distributed in Cerrado areas and transitional regions with the Caatinga in Northeastern Brazil, whose fruits exhibit significant nutritional, technological, and biofunctional potential. This review systematizes and critically analyzes the available scientific evidence regarding the fixed oil extracted from its fruits, addressing extraction methods, chemical composition, physicochemical parameters, nutritional value, technological applications, and the main bioactivities described in experimental models. Chromatographic and bromatological studies demonstrate that the oil presents a lipid profile characterized by the predominance of monounsaturated and saturated fatty acids, especially oleic acid and palmitic acid, in addition to the presence of carotenoids, phenolic compounds, and other bioactive lipophilic constituents. Available preclinical evidence indicates antioxidant, anti-inflammatory, wound-healing, gastroprotective, respiratory, anticonvulsant, and microbial resistance-modulating properties, suggesting potential applications in the food, pharmaceutical, cosmetic, and biotechnological fields. From the perspective of Food Science, the oil demonstrates characteristics compatible with lipid matrices of functional interest, although aspects related to oxidative stability, compositional standardization, sensory acceptability, and industrial scale-up remain insufficiently explored. Additionally, important limitations persist regarding the scarcity of systematic toxicological studies, the absence of clinical trials in humans, and the limited elucidation of the molecular mechanisms involved in the observed bioactivities. Although C. coriaceum presents promising biotechnological potential, its translational application still depends on further multidisciplinary studies integrating chemical standardization, toxicological safety, and technological development. Full article

Background: Alcohol use disorder (AUD) is a grave mental health condition that can result in significant health and social consequences. The medications Naltrexone and Nalmefene are indicated for the treatment of AUD, with Naltrexone having received the most extensive research attention. Methods: The majority of papers assessing universal measures of alcohol consumption employed two primary metrics: total alcohol consumption (TAC) and the number of days per month where individuals engaged in heavy drinking (HDD). Indicators pertaining to the maintenance of complete abstinence were excluded due to the absence of sufficient data. The safety of both substances was also assessed, as were the frequency of side effects and independent patient dropout. The study also incorporated practical factors of the therapy, such as the route of administration, dosage regimen, and the drug’s patient convenience, which can have a significant impact on adherence to therapy. Results: Nalmefene, administered in an “as needed” regimen, demonstrated statistically significant activity in reducing HDD and total alcohol consumption (TAC) among patients with AUD, particularly those with elevated World Health Organization (WHO) DRL risk. Preliminary findings from the ESENSE1 (Efficacy of Nalmefene in Alcohol Dependence; the first phase III study), ESENSE 2 (Efficacy of Nalmefene in Alcohol Dependence, the second phase III study), and SENSE (the final phase III long term-safety and cost-effectiveness study) studies indicate a substantial decrease in HDD and TAC following the initial month of treatment. These effects persist throughout the subsequent follow-up period. Several Japanese studies have corroborated the effectiveness of Nalmefene, demonstrating its efficacy across both short-term and long-term applications. Furthermore, these studies have substantiated its safety profile, indicating that there is no inherent risk of addiction or the emergence of withdrawal symptoms. The mild nature of adverse events (most commonly nausea and dizziness) led to a relatively low discontinuation rate of Nalmefene treatment. A subsequent study, employing a recognized methodology, corroborated the efficacy of psychosocial support in enhancing treatment outcomes. Meta-analyses demonstrate that Naltrexone exhibits comparable efficacy in reducing the frequency and severity of alcohol consumption. In select populations, the injectable form (LAI) of this pharmaceutical agent facilitates less frequent dosing, which is advantageous for the treatment process. A comparison of Nalmefene and Naltrexone reveals that the latter does not demonstrate a significant impact on the likelihood of individuals returning to heavy alcohol consumption. Conclusions: In the treatment of AUD, both naltrexone and nalmefene have been shown to yield positive outcomes, particularly in terms of reducing the HDD and TAC. According to the World Health Organization (WHO) classification, Nalmefene is indicated for individuals with a high risk of developing serious conditions. It has been demonstrated to produce rapid and sustained results while exhibiting a favorable safety profile, characterized by the absence of significant adverse effects. Naltrexone is a medication that has proven to be effective. LAI may have a positive impact on the efficacy of treatment. Full article