Search Results (452)

Background/Objectives: The aim of our research was to understand how excipients, unit operations, and process parameters impact processability and resulting properties, performance, and stability of tablets containing bovine lactoferrin, a cohesive biomacromolecule. Methods: Microcrystalline cellulose (MCC), croscarmellose (xCMC), lactose (LAC), hydroxypropyl methylcellulose (HPMC), and sodium stearyl fumarate (SSF) were used to produce various tablet formulations containing lactoferrin across a concentration range of 5 to 45%, targeting immediate- or controlled release performance. Tablets were made either by direct compression or via dry granulation followed by tableting. In addition to release performance, tablet attributes were characterized for tensile strength, friability, weight uniformity, and content uniformity. Results: Acceptable tablet tensile strength, friability, and performance were obtained for lactoferrin concentrations ranging from 15 to 45%, using a variety of excipients and manufacturing approaches. In several cases, dry granulation improved content uniformity. Excipient choice and tablet compression force impacted drug release, particularly when MCC alone was used as dry binder for immediate release. Dry granulation impacted tablet tensile properties, but did not significantly impact release performance. Lactoferrin–excipient compatibility was demonstrated for up to 2 years in ambient laboratory conditions. Conclusions: The study demonstrates that robust tablets can be produced using excipients and processes amenable to scale-up for industrial production. Consistent, stable, and suitably performing tablets were successfully produced using a variety of excipients, processing approaches, and across a broad concentration range with this cohesive biomacromolecule active pharmaceutical ingredient (API). Both immediate- and controlled release performance modes were possible. Full article

Vervain (Verbena officinalis L., Verbenaceae family) is a perennial plant which grows widely in Europe. It is rich in iridoids, phenolic acids, phenylpropanoid glycosides, flavonoids and terpenoids. Verbena has traditionally been used in folk medicine to calm the nervous system, but there is a lack of scientific data about it. The aim of this study was to explore and characterise the chemical profile and neurotropic effects of V. officinalis dry extracts and their amino acid-based preparations. We determined a total of eight main phenolic compounds and 17 amino acids in the V. officinalis dry extracts. To evaluate the neurotropic effects of the verbena extracts, the following behavioural pharmacology tests were used: Open Field Test, Elevated Plus Maze, Black-and-White Box Test and Tail Suspension Test. The dry aqueous–ethanolic extract (extractant 70% ethanol) demonstrated strong anxiolytic and antidepressant effects, while its dry modified extracts with valine and arginine consistently exhibited pronounced sedative activity across all studies. For example, the Tail Suspension Test demonstrated that the total immobility time in animals receiving the dry aqueous–ethanolic extract was the lowest, being 1.22-fold (p < 0.05) lower than in control animals and 2.25-fold (p < 0.05) lower than in the animals treated with the reference drug preparation (“Sedaphyton”). A novel aqueous-based gel formulation feasible for semi-solid extrusion (SSE) 3D printing was designed. This printing gel enables the fabrication of new oral dosage forms for V. officinalis dry extracts. The effects of pharmaceutical preparations on the human central nervous system require clinical studies. Full article

Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV antigenic proteins (K78R, A104R, E120R, E183L, D117L, and H171R) were fused with the Lactiplantibacillus plantarum WCFS1 surface anchor LP3065 (LPxTG motif) to generate recombinant Lactiplantibacillus plantarum NC8 (rNC8) strains. The surface expression was confirmed using immunofluorescence and Western blotting assays. Additionally, the dendritic cell-targeting peptides (DCpep) were co-expressed with each antigen protein. Mice were immunized at a dosage of 10⁹ colony-forming units (CFU) per strain per mouse via intragastric (I.G.), intranasal (I.N.), and intravenous (I.V.) routes. The bacterial mixture was heat-inactivated by boiling for 15 min to destroy viable cells while preserving antigenic structures. I.V. administration caused no hypersensitivity, confirming the method’s safety and effectiveness. Results: Following I.G. administration, rNC8-E120R, rNC8-E183L, rNC8-K78R, and rNC8-A104R induced significant levels of secretory immunoglobulin A (sIgA) in fecal samples, whereas rNC8-H171R and rNC8-D117L failed to induce a comparable response. Meanwhile, rNC8-D117L, rNC8-K78R, and rNC8-A104R also elicited significant levels of sIgA in bronchoalveolar lavage fluid (BALF). Following I.N. immunization, rNC8-E120R, rNC8-K78R, and rNC8-A104R significantly increased sIgA levels in both fecal and BALF immunization. In contrast, I.V. immunization with heat-inactivated rNC8-K78R and rNC8-A104R induced robust serum IgG titers, whereas the remaining antigens elicited minimal or insignificant responses. Flow cytometry analysis revealed expanded CD3⁺CD4⁺ T cells in mice immunized via the I.N. and I.G. and CD3⁺CD4⁺ T cells only in those immunized via the I.N. route. Th1 responses were also significant in the sera of mice immunized via the I.G. and I.N. routes. Conclusions: The rNC8 multiple-antigen cocktail elicited strong systemic and mucosal immune responses, providing a solid foundation for the development of a probiotic-based vaccine against ASF. Full article

Background/Objectives: Smart Formulation is an artificial intelligence-based platform designed to predict the Beyond Use Dates (BUDs) of compounded oral solid dosage forms. The study aims to develop a decision-support tool for pharmacists by integrating molecular, formulation, and environmental parameters to assist in optimizing the stability of extemporaneous preparations. Methods: A tree ensemble regression model was trained using a curated dataset of 55 experimental BUD values collected from the Stabilis database. Each formulation was encoded with molecular descriptors, excipient composition, packaging type, and storage conditions. The model was implemented using the KNIME platform, allowing the integration of cheminformatics and machine learning workflows. After training, the model was used to predict BUDs for 3166 APIs under various formulation and storage scenarios. Results: The analysis revealed a significant impact of excipient type, number, and environmental conditions on API stability. APIs with lower LogP values generally exhibited greater stability, particularly when formulated with a single excipient. Excipients such as cellulose, silica, sucrose, and mannitol were associated with improved stability, whereas HPMC and lactose contributed to faster degradation. The use of two excipients instead of one frequently resulted in reduced BUDs, possibly due to moisture redistribution or phase separation effects. Conclusions: Smart Formulation represents a valuable contribution to computational pharmaceutics, bridging theoretical formulation design with practical compounding needs. The platform offers a scalable, cost-effective alternative to traditional stability testing and is already available for use by healthcare professionals. Its implementation in hospital and community pharmacies may help mitigate drug shortages, support formulation standardization, and improve patient care. Future developments will focus on real-time stability monitoring and adaptive learning for enhanced precision. Full article

Background: The release study is a standard tool for the development, evaluation, and control of dosage forms. In the case of traditional drug delivery systems, it is conducted in accordance with the established principles available in the European and American Pharmacopoeias or guidelines proposed by registration agencies. The problem is the study of modern carriers, not yet described in compendia, which require adjustments to traditionally used methods. Objectives: The present study focuses on developing an optimal method for testing the release of cyclosporine (Cs, 0.5–4%) incorporated in solid lipid microparticles (SLM) dispersions (10%) intended for administration in the form of eye drops. This is a multicompartment lipid carrier that provides prolonged release of the active substance. Methods: Three methods of testing the release were compared: the dialysis bag method, the horizontal cells technique, and a method without a membrane. Results: During the analyses, the proper membrane was selected and the effect of the lysozyme enzyme on the release profile was analyzed. The effect of the composition of the acceptor fluid on the obtained results was also assessed. In the model without a membrane, up to 60% of the Cs was released within 30 min due to the burst effect. In horizontal chambers, no formulation released more than 14% of the Cs over 96 h, while at the same time, 60–70% of the Cs was released from the dialysis bag. Conclusions: Based on the obtained results, the dialysis bag method was selected to study the release of Cs from SLM without the need to use multicomponent artificial tear fluid as an acceptor medium. 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

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

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

The fatigue resistance of cement-stabilized macadam (CSM) plays a vital role in ensuring the long-term durability of pavement structures. However, limited cementitious material (CM) content often leads to high packing voids, which significantly compromise fatigue performance. Existing studies have rarely explored the coupled mechanism between pore structure and fatigue behavior, especially in the context of solid-waste-based CMs. In this study, a cost-effective alkali-activated sludge gasification slag (ASS) was proposed as a sustainable CM substitute for ordinary Portland cement (OPC) in CSM. A dual evaluation approach combining cross-sectional image analysis and fatigue loading tests was employed to reveal the effect pathway of void structure optimization on fatigue resistance. The results showed that ASS exhibited excellent cementitious reactivity, forming highly polymerized C-A-S-H/C-S-H gels that contributed to a denser microstructure and superior mechanical performance. At a 6% binder dosage, the void ratio of ASS–CSM was reduced to 30%, 3% lower than that of OPC–CSM. The 28-day unconfined compressive strength and compressive resilient modulus reached 5.7 MPa and 1183 MPa, representing improvements of 35.7% and 4.1% compared to those of OPC. Under cyclic loading, the ASS system achieved higher energy absorption and more uniform stress distribution, effectively suppressing fatigue crack initiation and propagation. Moreover, the production cost and carbon emissions of ASS were 249.52 CNY/t and 174.51 kg CO₂e/t—reductions of 10.9% and 76.2% relative to those of OPC, respectively. These findings demonstrate that ASS not only improves fatigue performance through pore structure refinement but also offers significant economic and environmental advantages, providing a theoretical foundation for the large-scale application of solid-waste-based binders in pavement engineering. 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

The utilization of steel slag (SS), fly ash (FA), and ground granulated blast furnace slag (GGBFS) as soil additives in construction represents a critical approach to achieving resource recycling of these industrial by-products. This study aims to activate the SS-FA-GGBFS composite with a NaOH solution and Na₂CO₃ and employ the activated solid waste blend as an admixture for lateritic clay modification. By varying the concentration of the NaOH solution and the dosage of Na₂CO₃ relative to the SS-FA-GGBFS composite, the effects of these parameters on the activation efficiency of the composite as a lateritic clay additive were investigated. Results indicate that the NaOH solution activates the SS-FA-GGBFS composite more effectively than Na₂CO₃. The NaOH solution significantly promotes the depolymerization of aluminosilicates in the solid waste materials and the generation of Calcium-Silicate-Hydrate and Calcium-Aluminate-Hydrate gels. In contrast, Na₂CO₃ relies on its carbonate ions to react with calcium ions in the materials, forming calcium carbonate precipitates. As a rigid cementing phase, calcium carbonate exhibits a weaker cementing effect on soil compared to Calcium-Silicate-Hydrate and Calcium-Aluminate-Hydrate gels. However, excessive NaOH leads to inefficient dissolution of the solid waste and induces a transformation of hydration products in the modified lateritic clay from Calcium-Silicate-Hydrate and Calcium-Aluminate-Hydrate to Sodium-Silicate-Hydrate and Sodium-Aluminate-Hydrate, which negatively impacts the strength and microstructural compactness of the alkali-activated solid waste composite-modified lateritic clay. Full article

An increasing number of soils, including those in EU countries, are affected by organic matter deficiency and the deterioration of nutrients, and using mineral fertilizers is often associated with negative environmental impacts. One of the basic recommendations for sustainable agriculture is to increase the proportion of organic fertilizers in crop production and preserve soil biodiversity. An increasingly common organic fertilizer is biogas plant digestate, the physical and chemical properties of which depend primarily on the waste material used in biogas production. However, the fertilizer value of this additive and its effects on the soil environment, including beneficial organisms, remain insufficiently studied. Soil macrofauna, particularly earthworms, play a crucial role in soil ecosystems, because they significantly impact the presence of plant nutrients, actively participate in forming soil structures, and strongly influence organic matter dynamics. The present study was undertaken to determine the effects of fertilizing a silt loam soil with the solid fraction of digestate in monoculture crop production on earthworm community characteristics and the resulting changes in selected soil physicochemical properties. The research was conducted at a single site, so the original soil characteristics across the experimental plots were identical. Plots were treated annually (for 3 years; 2021–2023) with different levels of digestate: DG100 (100% of the recommended rate; 30 t ha⁻¹), DG75 (75% of the recommended rate; 22.5 t ha⁻¹), DG50 (15 t ha⁻¹), DG25 (7.5 t ha⁻¹), and CL (a control plot without fertilizer). An electrical method was used to extract earthworms. Those found at the study site belonged to seven species representing three ecological groups: Dendrodrilus rubidus (Sav.), Lumbricus rubellus (Hoff.), and Dendrobaena octaedra (Sav.) (epigeics); Aporrectodea caliginosa (Sav.), Aporrectodea rosea (Sav.), and Octolasion lacteum (Örley) (endogeics); and Lumbricus terrestris (L.) (anecics). Significant differences in the abundance and biomass of earthworms were found between the higher level treatments (DG100, DG75, and DG50), and the lowest level of fertilization and the control plot (DG25 and CL). The DG25 and CL plots showed an average of 24.7% lower earthworm abundance and 22.8% lower biomass than the other plots. There were no significant differences in the earthworm metrics between the plots within each of the two groups (DG100, DG75, and DG50; and DG25 and CL). The most significant influence on the average abundance and average biomass of Lumbricidae was probably exerted by soil moisture and the annual dosage of digestate. A significant increase in the abundance and biomass of Lumbricidae was shown at plots DG100, DG75, and DG50 in the three successive years of the experiment. The different fertilizer treatments were found to have different effects on selected soil parameters. No significant differences were found among the values of the analyzed soil traits within each plot in the successive years of the study. Full article

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Background: Pharmaceutical compounding remains a predominantly manual process with limited innovation, particularly in non-sterile applications. This study explores the implementation of an automated compounding platform based on 3D printing to enhance precision, efficiency, and adaptability in pediatric corticosteroid formulations. Methods: Personalized hydrocortisone dosage forms were prepared in a hospital pharmacy setting using a proprietary excipient base and standardized procedures, including automated dosing and syringe heating when required. Three dosage forms—3.2 mg gel tablets, 2.8 mg water-free troches, and 1.2 mg orodispersible films (ODFs)—were selected to demonstrate the platform’s versatility and to address pediatric needs for varying strengths and dosage types. All products were prepared using a reproducible semi-solid extrusion (SSE)-based workflow with the consistent API-excipient blending and automated deposition. Results: Analytical testing confirmed that all formulations met pharmacopeial criteria for mass and content uniformity. The ODF and troche forms achieved rapid drug release, exceeding 75% within 5 min, while the gel tablet showed a slower release profile, reaching 86% by 60 min. Additionally, in-process homogeneity testing across syringe printing cycles confirmed the consistent API distribution. Conclusions: The results support the feasibility of integrating automated compounding technologies into pharmacy workflows. Such systems can improve accuracy, minimize variability, and streamline the production of customized pediatric medications, particularly for drugs with poor palatability or narrow therapeutic windows. Overall, this study highlights the potential of automation to modernize non-sterile compounding, and to better support individualized therapy. Full article

The development of eco-friendly surfactants is pivotal for enhanced oil recovery (EOR). In this study, a novel lignin-derived zwitterionic surfactant (DMS) was synthesized through a two-step chemical process involving esterification and free radical polymerization, utilizing renewable alkali lignin, maleic anhydride, dimethylamino propyl methacrylamide (DMAPMA), and sulfobetaine methacrylate (SBMA) as precursors. Comprehensive characterization via ¹H NMR, FTIR, and XPS validated the successful integration of amphiphilic functionalities. Hydrophilic–lipophilic balance (HLB) analysis showed a strong tendency to form stable oil-in-water (O/W) emulsions. The experimental results showed a remarkable 91.6% viscosity reduction in Xinjiang heavy crude oil emulsions at an optimum dosage of 1000 mg/L. Notably, DMS retained an 84.8% viscosity reduction efficiency under hypersaline conditions (total dissolved solids, TDS = 200,460 mg/L), demonstrating exceptional salt tolerance. Mechanistic insights derived from zeta potential measurements and molecular dynamics simulations revealed dual functionalities: interfacial modification by DMS-induced O/W phase inversion and electrostatic repulsion (zeta potential: −30.89 mV) stabilized the emulsion while disrupting π–π interactions between asphaltenes and resins, thereby mitigating macromolecular aggregation in the oil phase. As a green, bio-based viscosity suppressor, DMS exhibits significant potential for heavy oil recovery in high-salinity reservoirs, addressing the persistent challenge of salinity-induced inefficacy in conventional chemical solutions and offering a sustainable pathway for enhanced oil recovery. Full article