Search Results (1,037)

This study aimed to optimize the inoculation dosage and fermentation duration to enhance the protein content and reduce soluble oligosaccharides in soybean meal using Aspergillus oryzae and assessed its performance in dog food extrusion. A 3 × 5 factorial design was used to determine the optimal fermentation conditions. These conditions were applied to ferment soybean meal in bulk for nutritional analysis. Finally, the impact of fermentation on extrusion processing was assessed by formulating and extruding four diets: SBM (30% soybean meal), AMF (30% soybean meal with 1% Amaferm^®—A. oryzae biomass), FSBM (30% fermented soybean meal), and SPI (18% soy protein isolate). Diets were extruded with a single-screw extruder, and physical characteristics of kibbles, particle size distribution, and viscosity of raw mixes were analyzed. The optimal fermentation conditions were 1 × 10⁴ spore/g substrate for 36 h, which increased the crude protein content by 4.63% DM, methionine and cysteine total content by 0.15% DM, and eliminated sucrose, while significantly reducing stachyose, raffinose, and verbascose (95.22, 87.37, and 41.82%, respectively). The extrusion results showed that FSBM had intermediate specific mechanical energy (SME), in-barrel moisture requirements, and sectional expansion index (198.7 kJ/kg, 28.2%, and 1.80, respectively) compared with SBM (83.7 kJ/kg, 34.5%, and 1.30, respectively) and SPI (305.3 kJ/kg, 33.5%, and 2.55, respectively). The FSBM also exhibited intermediate particle size distribution and the least raw mix viscosity. These findings demonstrate that A. oryzae fermentation enhances the nutrient profile of soybean meal while improving extrusion efficiency and kibble quality, supporting its potential use as a sustainable pet food ingredient. Full article

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

Background/Objectives: Mammary carcinoma is a common disease in female dogs. Cannabidiol (CBD) can inhibit cell proliferation and induce apoptosis in human cancer cells. However, its low solubility in aqueous media requires solvents such as ethanol or dimethylsulfoxide that limit their dosage. Incorporating CBD into oil-in-water nanoemulsions (Nem) can improve its aqueous dispersibility. This study aimed to develop a CBD-Nem formulation and evaluate its effects on canine mammary cancer cell lines (CF41.Mg and IPC366) and non-cancer cells (MDCK). Methods: CBD-Nem was prepared with Miglyol 812 oil and Epikuron 145 V as the surfactant, and was characterized by analyzing size, morphology, zeta potential, release profile, and uptake/internalization. Moreover, the antitumor effects of CBD-Nem were evaluated in cancer cells through viability, proliferation, cell cycle, and migration–invasion assays. Results: CBD-Nem exhibited a monodisperse nanometric population (~150 nm), spherical shape, and negative zeta potential (~−50 mV). The in vitro release kinetics showed slow and sustained delivery at both pH 5.5 and pH 7.4. Rhodamine-Nem, as a fluorescent model of CBD-Nem, was taken up and homogenously internalized in CF41.Mg cells. CBD-Nem decreased the viability of cancer cells with a maximum effect at 50 µM and showed a lower toxicity in MDCK cells. Long-term efficacy (20 days) was evidenced by CBD-Nem at inhibiting colony formation in cancer cells. Furthermore, CBD-Nem reduced the proportion of cells in the G2-M phase, induced apoptosis, and inhibited the migration and invasion of CF41.Mg cells. Conclusions: CBD-Nem exhibited an in vitro antitumor effect, which supports its study in dogs with mammary carcinoma. Full article

This review explores the potential of magistral formulas (MFs) as a viable option to meet the needs of neonates, given the lack of adequate therapies for this vulnerable group. The scientific literature on medicines available for neonates is limited. The physiological differences between neonates and adults make it difficult to formulate these medicines. In addition, there are a variety of difficulties in conducting research on neonates: few clinical trials are performed, and there is frequent use of unauthorized medicines. Pharmacokinetics in neonates was investigated in comparison to adults, and different aspects of the absorption, distribution, metabolism, and excretion were observed. One of the main problems is the different pharmacokinetics between the two populations. It is necessary to promote and allow research related to pediatric drug design, approve a specific authorization for use in age-appropriate dosage forms, and improve the quality and availability of information on drugs. This study focused on the MFs typically used for pediatrics, specifically for neonates, analyzing the pharmaceutical forms currently available and the presence of indications and dosage recommendations of the European Medicines Agency. Medications were classified according to therapeutic group, as antihypertensives, corticosteroids, and antiepileptics. The use of off-label medicines remains high in neonatal intensive care units and in primary healthcare, besides in the preparation of MFs by pharmacists. The shortage of medicines specifically designed and approved for neonates is a serious problem for society. Neonates continue to be treated, on numerous occasions, with off-label medicines. Studies and research should be expanded in this vulnerable population group. Full article

Donepezil (DPZ) is an Alzheimer’s disease (AD) drug that promotes cholinergic neurotransmission and exhibits excellent acetylcholinesterase (AChE) selectivity. The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood–brain barrier (BBB). In order to overcome these limitations, various dosage forms aimed at delivering DPZ have been explored. This discussion will focus on the nose-to-brain (N2B) delivery system, which represents the most promising approach for brain drug delivery. Intranasal (IN) drug delivery is a suitable system for directly delivering drugs to the brain, as it bypasses the BBB and avoids the first-pass effect, thereby targeting the central nervous system (CNS). Currently developed formulations include lipid-based, solid particle-based, solution-based, gel-based, and film-based types, and a systematic review of the N2B research related to these formulations has been conducted. According to the in vivo results, the brain drug concentration 15 min after IN administration was more than twice as high those from other routes of administration, and the direct delivery ratio of the N2B system improved to 80.32%. The research findings collectively suggest low toxicity and high therapeutic efficacy for AD. This review examines drug formulations and delivery methods optimized for the N2B delivery of DPZ, focusing on technologies that enhance mucosal residence time and bioavailability while discussing recent advancements in the field. Full article

Background/Objectives: Hot-melt extrusion (HME) has gained prominence for the manufacture of sustained-release oral dosage forms, yet the application of wax-based matrices and their resilience to alcohol-induced dose dumping (AIDD) remains underexplored. This study aimed to develop and characterise wax-based sustained-release felodipine formulations, with a particular focus on excipient functionality and robustness against AIDD. Methods: Felodipine sustained-release formulations were prepared via HME using Syncrowax HGLC as a thermally processable wax matrix. Microcrystalline cellulose (MCC) and lactose monohydrate were incorporated as functional fillers and processing aids. The influence of wax content and filler type on mechanical properties, wettability, and drug release behaviour was systematically evaluated. Ethanol susceptibility testing was conducted under simulated co-ingestion conditions (4%, 20%, and 40% v/v ethanol) to assess AIDD risk. Results: MCC-containing tablets demonstrated superior sustained-release characteristics over 24 h, showing better wettability and disintegration. In contrast, tablets formulated with lactose monohydrate remained structurally intact during dissolution, overly restricting drug release. This limitation was effectively addressed through granulation, where reduced particle size significantly improved surface accessibility, with 0.5–1 mm granules achieving a satisfactory release profile. Ethanol susceptibility testing revealed divergent behaviours between the two filler systems. Unexpectedly, MCC-containing tablets showed suppressed drug release in ethanolic media, likely resulting from inhibitory effect of ethanol on filler swelling and disintegration. Conversely, formulations containing lactose monohydrate retained their release performance in up to 20% v/v ethanol, with only high concentrations (40% v/v) compromising matrix drug-retaining functionality and leading to remarkably increased drug release. Conclusions: This study highlights the pivotal role of excipient type and constitutional ratios in engineering wax-based sustained-release formulations. It further contributes to the understanding of AIDD risk through in vitro assessment and offers a rational design strategy for robust, alcohol-resistant oral delivery systems for felodipine. Full article

The number of newly developed substances with poor water solubility continually increases. Therefore, specialized formulation strategies are required to overcome the low bioavailability often associated with this property. This review provides an overview of novel physical modification strategies discussed in the literature over the past decades and focuses on oral dosage forms. A distinction is made between ‘brick-dust’ molecules, which are characterized by high melting points due to the solid-state properties of the substances, and ‘grease-ball’ molecules with high lipophilicity. In general, the discussed strategies are divided into the following three main categories: drug nanoparticles, solid dispersions, and lipid-based formulations. Full article

Background/Objectives: Although technology has progressed and novel dosage forms have been developed, tablets are still the most used form of medication. However, the present manufacturing methods of these oral solid dosage forms offer limited capacity for personalized treatment and adaptable dosing. Personalized therapy, with a few exceptions, is not yet a part of routine clinical practice. Drug printing could be a possible approach to increase the use of personalized therapy. The aim of this work was to investigate the role of surface tension and the viscosity of inks in the formation of the printing pattern and to investigate how the porosity of substrate tablets influences the behavior of inks on the surface. Methods: Spray-dried mannitol served as a binder and filler, while magnesium stearate functioned as a lubricant in the preparation of substrate tablets. Brilliant Blue dye was a model “drug”. The ink formulation was applied to the substrates in three varying quantities. Results: Increasing the viscosity enhanced the drug content, potentially improving printing speed and pattern accuracy. However, it negatively impacted the dosing accuracy due to nozzle clogging and prolonged drying time. Viscosity had a significantly higher impact on the ink behavior than surface tension. Lowering the surface tension improved the dosing accuracy and reduced the drying time but resulted in smaller drop sizes and decreases in pattern accuracy. Reducing the substrate porosity led to longer drying times and diminished pattern accuracy. Conclusions: A target surface tension of around 30 mN/m is suggested for inkjet printing. It is necessary to further investigate the applicability of the technology with solutions of inks with high viscosity and low surface tension, including the API. Full article

This study investigates cement–bentonite slurries with hydration accelerators for borehole backfilling applications in infrastructure reconstruction projects. Two formulations with different accelerator dosages (5 and 10 kg/m³) were evaluated through combined experimental testing and Moving Particle Semi-implicit (MPS) numerical modeling to optimize material performance. The research focuses on time-dependent rheological evolution and its impact on construction performance, particularly bleeding resistance and workability retention. Experimental flow tests revealed that both formulations maintained similar initial flowability (240–245 mm spread diameter), but the higher accelerator dosage resulted in 33% flow reduction after 60 min compared to 12% for the lower dosage. Bleeding tests demonstrated significant improvement in phase stability, with bleeding rates reduced from 2.5% to 1.5% when accelerator content was doubled. The MPS framework successfully reproduced experimental behavior with prediction accuracies within 3%, enabling quantitative analysis of time-dependent rheological parameters through inverse analysis. The study revealed that yield stress evolution governs both flow characteristics and bleeding resistance, with increases several hundred percent over 60 min while plastic viscosity remained relatively constant. Critically, simulations incorporating time-dependent viscosity changes accurately predicted bleeding behavior, while constant-viscosity models overestimated bleeding rates by 60–130%. The higher accelerator formulation (10 kg/m³) provided an optimal balance between initial workability and long-term stability for typical borehole backfilling operations. This integrated experimental–numerical approach provides practical insights for material optimization in infrastructure reconstruction projects, particularly relevant for aging infrastructure requiring proper foundation treatment. The methodology offers construction practitioners a robust framework for material selection and performance prediction in borehole backfilling applications, contributing to improved construction quality and reduced project risks. Full article

This study uses ordinary Portland–sulfate–silicate composite cement as the matrix and investigates the effects of water–cement ratio, HPMC dosage, and PCS dosage on the performance of specialized grouting materials for subway structure repair during operation through single-factor experiments and orthogonal experiments. Multifactorial variance analysis was employed to quantitatively evaluate the sensitivity of each factor and their interactions to slurry flowability, setting time, anti-dispersibility, and compressive strength. The results show that the water–cement ratio is the most critical factor affecting the performance of the grouting material, with extremely significant impacts on all performance indicators; HPMC dosage significantly affects flowability, setting time, and anti-dispersibility; PCS dosage primarily influences 2 h compressive strength; the interaction between water–cement ratio and HPMC dosage has a significant impact on anti-dispersibility. Principal component analysis revealed the trade-off relationship between flowability, setting time, and strength. The study established a sensitivity ranking for the performance of specialized grouting materials: water–cement ratio > HPMC dosage > PCS dosage > interaction, providing a theoretical basis and methodological reference for the formulation optimization of specialized grouting materials for subway structure repair during operation. Full article

Plant polyphenols have emerged as potent bioactive molecules that can modulate key cellular pathways associated with aging and chronic disorders. The Mediterranean diet and the traditional Japanese style of life are rich in polyphenol-containing foods and beverages, and epidemiological evidence links these dietary patterns to increased longevity and reduced morbidity. This narrative review examines the chemical description of plant polyphenols, their mechanisms of action, including anti-inflammatory, antioxidant, and hormetic effects, and how supplementation or a diet rich in these compounds may provide further life extension. We discuss the major classes of polyphenols present in the Mediterranean dietary pattern (e.g., resveratrol and hydroxytyrosol) and in the Japanese diet (e.g., epigallocatechin gallate and soy isoflavones), comparing their biological behaviors and cooperative effects on metabolic, cardiovascular, and neurodegenerative conditions. We also examine a few preclinical and clinical studies that explain the beneficial impact of these chemicals on aging-associated biomarkers. Furthermore, both dietary habits are characterized by low consumption of processed foods and sugary carbonated drinks and reduced utilization of deep-frying with linoleic acid-rich oils, a practice that reduces the formation of harmful lipid peroxidation products, notably 4-hydroxynonenal, known to be implicated in accelerating the aging process. The Mediterranean dietary pattern is also characterized by a low/moderate daily consumption of wine, mainly red wine. This work debates emerging evidence addressing issues of bioavailability, dosage optimization, and formulation technologies for polyphenol supplementation, also comparing differences and similarities with the vegan and vegetarian diets. We also explore how these chemicals could modulate epigenetic modifications that affect gene expression patterns pertinent to health and aging. In conclusion, we aim to show a consolidated framework for the comprehension of how plant polyphenols could be utilized in nutritional strategies for potentiating life expectancy while stimulating further research on nutraceutical development. Full article

To broaden clean asphalt modification methods, this study employs a composite polymer of maleic anhydride-grafted styrene-butadiene-styrene (MA-g-SBS) and styrene-butadiene-styrene (SBS) as a modifier. The composite is formulated into polymer latex and used to modify emulsified asphalt. Routine performance tests were conducted on MA-g-SBS/SBS composite latex-modified emulsified asphalt (MSMEA) with varying ratios to determine the optimal composition. The ideal ratio was found to be MA-g-SBS:SBS = 1:4. Subsequently, conventional property tests, rheological analyses, microphase structure observations, and bending beam creep tests were conducted on MSMEA with the optimal ratio to assess the impact of the composite latex on asphalt performance. Findings indicated that increasing the latex content significantly enhanced the softening point and ductility while reducing penetration. These macroscopic improvements were notably superior to those achieved with single SBS latex modification. Fluorescence microscopy revealed that at low dosages, the MA-g-SBS/SBS composite dispersed uniformly as point-like structures within the asphalt. At higher dosages (above 5%), a distinct network structure emerged. The addition of the composite latex raised the complex shear modulus and rutting factor while reducing the phase angle, with pronounced fluctuations observed between 4% and 5% dosages. This suggests a substantial enhancement in the high-temperature performance of the emulsified asphalt, attributed to the formation of the network structure. FT-IR results confirmed that a chemical reaction occurred during the modification process. Additionally, the bending beam creep test demonstrated that the composite latex reduced asphalt brittleness and improved its low-temperature performance. Full article

Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard capsules. However, the current trends in pharmacy and medicine are centred on personalised drug therapy and drug delivery systems (DDSs). Therefore, 3D printing is an interesting technique for designing and preparing novel personalised pharmaceuticals for flavonoids. The aim of the present study was to develop aqueous polyethylene oxide (PEO) gel inks loaded with rutin for semisolid extrusion (SSE) 3D printing. Methods. Rutin (a model substance for therapeutic flavonoids), Tween 80, PEO (MW approx. 900,000), ethanol, and purified water were used in PEO gels at different proportions. The viscosity and homogeneity of the gels were determined. The rutin–PEO gels were printed with a bench-top Hyrel 3D printer into lattices and discs, and their weight and effective surface area were investigated. Results. The key SSE 3D-printing process parameters were established and verified. The results showed the compatibility of rutin as a model flavonoid and PEO as a carrier polymer. The rutin content (%) and content uniformity of the 3D-printed preparations were assayed by UV spectrophotometry and high-performance liquid chromatography (HPLC). Conclusions. The most feasible aqueous PEO gel ink formulation for SSE 3D printing contained rutin 100 mg/mL and Tween 80 50 mg/mL in a 12% aqueous PEO gel. The 3D-printed dosage forms are intended for the oral administration of flavonoids. Full article

Embedded printing of soft materials relies on yield-stress support matrices to prevent sagging and enable freeform fabrication. The rheological parameters of the matrix material directly influence critical printing outcomes such as strand positioning, cavity formation, structural stability, and defect suppression in embedded printing. Despite widespread use of Carbopol^® formulations, a systematic rheological characterization of ETD2020 across relevant polymer concentrations and pH levels for embedded printing is lacking. Here, we implement a full-factorial design with polymer concentrations from $0.1\mathrm{wt}\%$ to $0.9\mathrm{wt}\%$ and triethanolamine dosages of 30–$50$µL per $100\mathrm{g}$. Steady-shear ($0.001$–$200{\mathrm{s}}^{-1}$) and oscillatory ($1\mathrm{Hz}$) rheometry yielded Herschel–Bulkley parameters ${\tau }_y$, k, n as well as storage and loss modulus $G^{\prime }$/$G^{\prime \prime }$. All formulations exhibited pronounced shear-thinning, with ${\tau }_y$ increasing nonlinearly from <$1\mathrm{Pa}$ to $41.1\mathrm{Pa}$ and $G^{\prime }$ reaching $\approx 400\mathrm{Pa}$ at $0.9\mathrm{wt}\%$. A five-hour window of invariant rheology was identified, followed by a $\Delta {\tau }_y\approx 10\mathrm{Pa}$ increase after five days, indicating delayed polymerization. The comprehensive material characterization defines a rheological window for ETD2020 and facilitates simulation-based modeling and the targeted tuning of matrix properties. Heatmaps provide an interpolated depiction of combined carbomer and triethanolamine concentrations, enabling tunable support matrices for embedded printing. Full article

Background/Objectives: The precise control of drug absorption through the nasal mucosa following intranasal administration can be achieved through optimal formulation development that considers the nasal retention properties of the administered dosage form. This study aimed to quantitatively elucidate the effect of formulation type on nasal residence time in vivo. Methods: The nasal residence behavior of various formulation types, including solutions, particulates, and powders, was estimated in rats. Furthermore, the effect of mucoadhesive polymers on the nasal residence time was investigated using gel and powder dosage forms of sodium alginate. Results: The nasal retention behavior of the formulation in the nasal cavity differed depending on the dosage form. The polystyrene microparticles and lactose powder, a non-adhesive powder, were quickly eliminated into the nasopharynx, whereas the solution remained in the nasal cavity longer than the other formulations. The clearance behavior of the solution was investigated, and it was found that the solution was quickly transported to the stomach without being retained in the esophagus. The disappearance of the gel and powder with the mucoadhesive polymer was different, with the powder clearing faster. This difference in clearance is thought to be due to the powder being cleared before dissolving and diffusing into the nasal mucus. Conclusions: It has been clearly shown that the nasal residence behavior differed depending on the dosage forms. The addition of mucoadhesive polymers was effective in improving the nasal residence of the drug, and more-effective formulations for nasal application can be developed by combining optimal dosage forms, such as powders and gels. Full article