Search Results (447)

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

Background/Objectives: Controlling the critical quality attributes (CQAs), such as granule moisture level and particle size distribution, that impact product performance is essential for ensuring product quality in medicine manufacture. Oral solid dosage forms, such as tablets, often require appropriate powder flow for compaction and filling. Spray-dried fluidized bed granulation (FBG) is a key unit operation in the preparation of granulated powders. The determination of particle sizes in FBG using near-infrared spectroscopy (NIR) has been considered in the literature. Herein, for the first time, NIR is combined with process parameters to achieve improved prediction of the particle sizes in FBG. Methods: An inline model for particle size determination using both NIR and FBG process parameters was developed using the partial least square (PLS) method, or ‘merged-PLS model’. The particle size was predicted at the end point of the process, i.e., the last 10% of the particle-size data for each batch run. An additional two analyses included a merged-PLS model with 12 batches: (1) where nine batches were training and three batches were a test set; and (2) where 11 batches were training and one was a test batch. Results: For all considered particle size fractions, Dv10, Dv25, Dv50, Dv75, and Dv90, an improved root-mean-squared error of prediction (RMSEP) is obtained for the merged-PLS model compared to the NIR-only PLS model and compared to the process parameters alone model. Improved RMSEP is also achieved for the additional two analyses. Conclusions: The improved prediction performance of endpoint particle sizes by the merged-PLS model can help to enhance both the process understanding and the overall control of the FBG process. Full article

Improving the manufacturability of drug formulations via direct compression has been of great interest for the pharmaceutical industry. Selecting excipients plays a vital role in obtaining a high-quality product without the wet granulation processing step. In particular, for diluents which are usually present in a larger amount in a formulation, choosing the correct one is of utmost importance in the production of tablets via any method. In this work, we assessed the possibility of manufacturing a small-molecule drug product, omeprazole, which has been historically manufactured via a multi-step processes such as wet granulation and multiple-unit pellet system (MUPS). For this purpose, four prototypes were developed using several diluents: a co-processed excipient (Microcelac^®), two granulated forms of alpha-lactose monohydrate (Tablettose^® 70 and Tabletose^® 100), and a preparation of microcrystalline cellulose (Avicel^® PH102) and lactose (DuraLac^® H), both of which are common excipients without any enhancement. The tablets were produced using a single punch tablet press and thoroughly characterized physically and chemically in order to assess their functionality and adherence to drug product specifications. The direct compression process was used for the manufacturing of all proposed formulations, and the prototype formulated using Microcelac^® showed the best results and performance during the compression process. In addition, it remained stable over twelve months under 25 °C/60% RH conditions. Full article

Background/Objectives: Difenoconazole (DFC) is a broad-spectrum fungicide. However, its application is limited due to poor aqueous solubility. Drugs with low solubility can be better absorbed using nanostructured lipid carriers (NLCs). Hence, the application of DFC in an NLC delivery system is proposed. Methods: Difenoconazole-loaded nanostructured lipid carriers (DFC-NLCs) with different solid–liquid lipid ratios were prepared by solvent diffusion method. Key physicochemical parameters, including particle diameter, surface charge (zeta potential), drug encapsulation efficiency, and morphological characteristics, were systematically characterized. Using Rhizoctonia solani (R. solani) as the model strain, inhibitory efficiency of DFC-NLC dispersion was compared with that of commercial dosage forms, such as 25% DFC emulsifiable concentrate (DFC-EC) and 40% DFC suspension concentrate (DFC-SC). Additionally, uptakes of DFC-NLC dispersions in R. solani were further observed by fluorescence probe technology. The safety profiles of DFC-NLCs and commercial dosage forms were evaluated using zebrafish as the model organism. Acute toxicity studies were conducted to determine the maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC₁₀). Developmental toxicity studies were performed to observe toxic phenotypes. Results: DFC-NLC dispersions were in the nanometer range (≈200 nm) with high zeta potential, spherical in shape with encapsulation efficiency 69.1 ± 1.8%~95.0 ± 2.6%, and drug loading 7.1 ± 0.3%~9.7 ± 0.6% determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Compared with commercial dosage forms, the antifungal effect of the DFC-NLC on R. solani was significantly improved in in vitro antibacterial experiments (p < 0.05). The 50% effective concentration (EC₅₀) values were 0.107 mg·L⁻¹ (DFC-NLC), 0.211 mg·L⁻¹ (DFC-EC), and 0.321 mg·L⁻¹ (DFC-SC), respectively. The uptakes of FITC-labeled DFC-NLC demonstrated that an NLC was appropriate to deliver DFC into pathogen to enhance the target effect. In safety assessment studies, DFC-NLCs exhibited a superior safety profile compared with commercial formulations (p < 0.05). Conclusions: This study investigates the feasibility of NLCs as delivery systems for poorly water-soluble fungicides, demonstrating their ability to enhance antifungal efficacy and reduce environmental risks. Full article

Background/Objectives: Rivaroxaban, an oral anticoagulant, shows poor aqueous solubility, posing significant challenges to its bioavailability and therapeutic efficiency. The present study investigates the improvement of rivaroxaban’s solubility through the formation of different inclusion complexes with three cyclodextrin derivatives, such as β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by lyophilization in order to stabilize the complexes and improve dissolution characteristics of rivaroxaban. Methods: The physicochemical properties of the individual compounds and the three lyophilized complexes were analysed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Results: FTIR spectra confirmed the formation of non-covalent interactions between rivaroxaban and the cyclodextrins, suggesting successful encapsulation into cyclodextrin cavity. SEM images revealed a significant morphological transformation from the crystalline structure of pure rivaroxaban and cyclodextrins morphologies to a more porous and amorphous matrix in all lyophilized complexes. XRD patterns indicated a noticeable reduction in drug crystallinity, supporting enhanced potential of the drug solubility. TGA analysis demonstrated improved thermal stability in the inclusion complexes compared to the individual drug and cyclodextrins. Pharmacotechnical evaluation revealed that the obtained formulations (by comparison with physical mixtures formulations) possessed favorable bulk and tapped density values, suitable compressibility index, and good flow properties, making all suitable for direct compression into solid dosage forms. Conclusions: The improved cyclodextrins formulation characteristics, combined with enhanced dissolution profiles of rivaroxaban comparable to commercial Xarelto^® 10 mg, highlight the potential of both cyclodextrin inclusion and lyophilization technique as synergistic strategies for enhancing the solubility and drug release of rivaroxaban. Full article

The synergistic mechanism between alkali activation and carbonation in fly ash recycled aggregate concrete (FRAC) remains a critical challenge for enhancing durability and promoting solid waste utilization. This study systematically investigates the effects of CaO-based alkali activator dosages (0%, 4%, 8%, 12%) on carbonation resistance, compressive strength, and pore structure evolution. The results demonstrated 8% CaO maximized compressive strength (48.6 MPa, 10.76% higher than the control group) and minimized porosity (22.87% vs. 39.33% in untreated samples), with enhanced carbonation resistance (35% depth reduction after 28 days). Fractal dimension (FD) analysis revealed that 8% dosage optimized pore complexity (FD > 1.9), forming a dense C–S–H/AFt network that suppressed CO₂ diffusion. CaO addition introduces embodied carbon (9.84 kg CO₂/m³), and the synergy between fly ash’s cement replacement (120 kg CO₂/m³ reduction) and extended service life (theoretically, 15–20 years) ensures a net carbon benefit. These findings establish 8% as a critical threshold for optimizing alkali activation efficiency and durability in low-carbon concrete design. These findings offer theoretical and technical foundations for low-carbon concrete design and sustainable solid waste recycling in construction. Full article