Search Results (105)

Background/Objectives: Long-acting injections (LAIs) are innovative drug delivery systems that improve patient compliance by maintaining therapeutic drug levels over extended periods. Micro- and nanosuspensions are commonly used in LAIs to enhance bioavailability, but their thermodynamic instability poses challenges, including particle aggregation and growth. This study aimed to evaluate the impact of two helping processes—vehicle thermal treatment and high-shear homogenization—on the stability and manufacturing efficiency of aripiprazole monohydrate (AM) suspensions. Methods: AM suspensions containing sodium carboxymethyl cellulose (CMCNa), mannitol and disodium phosphate in water for injections (WFIs) were prepared using a combination of thermal treatment of the vehicle solution, high-shear homogenization and bead milling. Four manufacturing variants were tested to assess the influence of these processes on particle size distribution (PSD), viscosity and stability during a 3-month accelerated stability study. Molecular weight changes in CMCNa from thermal treatment were analyzed using size exclusion chromatography with multiangle scattering (SEC-MALS), and PSD was measured using laser diffraction. Results: Thermal treatment of the vehicle solution had minimal impact on CMCNa molecular weight, preserving its functionality. High-shear homogenization during bead milling significantly reduced particle aggregation, resulting in improved PSD and reduced viscosity. Synergistic effects of the two helping processes used in one manufacturing process were observed, which led to superior stability and minimal changes in PSD and viscosity during storage. Batches without the helping processes exhibited increased particle size and viscosity over time, indicating reduced suspension stability. Conclusions: Incorporating vehicle thermal treatment and high-shear homogenization during bead milling enhances the stability and manufacturing efficiency of AM suspensions. These findings underscore the importance of optimizing laboratory-scale processes to ensure the quality and safety of pharmaceutical suspensions. Full article

Background/Objectives: This study aimed to develop a dry powder inhalation (DPI) formulation of rivaroxaban (RVX) using a combination of bead milling (BM) and jet milling (JM) to enhance lung-targeted delivery for the effective treatment of pulmonary embolism while minimizing systemic exposure. Methods: A carrier-free DPI formulation of RVX was developed using sequential BM and JM, with L-leucine incorporated at various concentrations (1%, 5%, and 10%) as a force control agent. The formulations were characterized for particle morphology, size distribution, crystallinity, and thermal properties. The in-vitro aerodynamic performance was evaluated using a next-generation impactor, while ex-vivo studies assessed anticoagulant activity. Pharmacokinetic and tissue distribution studies were carried out in Sprague Dawley rats following intratracheal administration, and the effects of inhaled RVX were compared with those of oral administration. Results: The optimized BM-JM-5L formulation achieved a Dv50 of 2.58 ± 0.01 µm and a fine particle fraction of 72.10 ± 2.46%, indicating suitability for pulmonary delivery. The two-step milling effectively reduced particle size and enhanced dispersibility without altering RVX’s physicochemical properties. Ex-vivo anticoagulation tests confirmed maintained or improved activity. In-vivo studies showed that pulmonary administration (5 mg/kg) led to a 493-fold increase in lung drug concentration and 2.56-fold higher relative bioavailability vs. oral dosing, with minimal heart tissue accumulation, confirming targeted lung delivery. Conclusions: The two-step milled RVX DPI formulations, particularly BM-JM-5L with 5% leucine, demonstrated significant potential for pulmonary administration by achieving high local drug concentrations, rapid onset, and improved bioavailability at lower doses. These findings highlight the feasibility of RVX as a DPI formulation for pulmonary delivery in treating pulmonary embolism. Full article

Background: We previously reported that carbopol hydrogels incorporating indomethacin nanoparticles (IMC NPs) improved the low permeability and bioavailability of skin formulations in transdermal drug delivery systems. However, the combination of NPs with other types of hydrogels has not been sufficiently explored to date. Therefore, this study investigated propylene glycol (PG)/polyvinyl alcohol (PVA) hydrogel as an alternative base to carbopol hydrogel for incorporating IMC NPs. Methods: IMC NPs were prepared using bead milling treatment, and these NPs were incorporated into PG/PVA hydrogel (IMC-NP@PG/PVA hydrogel). The IMC concentration was measured using the HPLC method, and seven-week-old Wistar rats were used to evaluate skin absorption. Results: Bead milling reduced the IMC particle size in the PG/PVA hydrogels to the nanoscale (30–200 nm) without altering its crystalline form. The IMC-NP@PG/PVA hydrogel exhibited enhanced uniformity, solubility, and drug release compared to the IMC microparticle-loaded PG/PVA hydrogel (IMC-MP@PG/PVA hydrogel), with a 1.44-fold greater area under the concentration–time curve. Transdermal permeability studies revealed that IMC-NP@PG/PVA had 2.36-fold higher absorption than the IMC-MP@PG/PVA hydrogel, with dissolved IMC permeating the skin. Pharmacokinetics in the rats showed significantly increased plasma levels, absorption rates, and bioavailability for IMC-NP@PG/PVA, demonstrating its superior delivery efficiency. Moreover, the skin absorption of IMC-NP@PG/PVA was higher than that of carbopol hydrogel. Conclusions: These findings highlight the potential of PG/PVA hydrogels as an effective base for transdermal drug delivery systems based on NPs. Full article

Microalgae have emerged as a sustainable and efficient source of protein, offering a promising alternative to conventional animal and plant-based proteins. Species such as Arthrospira platensis and Chlorella vulgaris contain protein levels ranging from 50% to 70% of their dry weight, along with a well-balanced amino acid profile rich in essential amino acids such as lysine and leucine. Their cultivation avoids competition for arable land, aligning with global sustainability goals. However, the efficient extraction of proteins is challenged by their rigid cell walls, necessitating the development of optimized methods such as bead milling, ultrasonication, enzymatic treatments, and pulsed electric fields. These techniques preserve functionality while achieving yields of up to 96%. Nutritional analyses reveal species-dependent digestibility, ranging from 70 to 90%, with Spirulina platensis achieving the highest rates due to low cellulose content. Functionally, microalgal proteins exhibit emulsifying, water-holding, and gel-forming properties, enabling applications in baking, dairy, and meat analogs. Bioactive peptides derived from these proteins exhibit antioxidant, antimicrobial (inhibiting E. coli and S. aureus), anti-inflammatory (reducing TNF-α and IL-6), and antiviral activities (e.g., Dengue virus inhibition). Despite their potential, commercialization faces challenges, including regulatory heterogeneity, high production costs, and consumer acceptance barriers linked to eating habits or sensory attributes. Current market products like Spirulina-enriched snacks and Chlorella tablets highlight progress, but food safety standards and scalable cost-effective extraction technologies remain critical for broader adoption. This review underscores microalgae’s dual role as a nutritional powerhouse and a source of multifunctional bioactives, positioning them at the forefront of sustainable food and pharmaceutical innovation. Full article

This study investigates the potential of additive-free extraction techniques to produce a proteolytically active yeast extract for use in the food industry. Brewer’s spent yeast, a by-product of the brewing industry, is utilized as a feedstock, and thus a new route for its valorization is proposed. Four methods of releasing these components while maintaining their intrinsic bioactivity are investigated: thermal autolysis, ultrasonication, cell milling and high-pressure homogenization. Thermal yeast autolysis resulted in the highest release of protease activity, with 2.45 ± 0.05 U/g_dm after 3 h incubation at 45 °C. However, autolysis poses challenges for automation, and thus a stop criterion, due to the lack of in-line enzyme activity assays,. While glass bead treatment gave the highest reproducibility, ultrasonication and high-pressure homogenization resulted in comparably high protease activities in the BSY extracts produced. Both methods, in the form of a cell mill and high-pressure homogenizer, are cell disruption methods that are already employed on an industrial scale. It has now been demonstrated that these methods can be used to produce proteolytically active yeast extracts from a previously considered waste stream. Full article

The limited water solubility of active compounds remains a significant challenge for efficient dermal drug delivery, particularly for BCS class IV drugs such as curcumin. This study aimed to enhance curcumin’s dermal penetration using two strategies: extracellular vesicles (EVs) and plantCrystals derived from soybeans. EVs were isolated using classical methods. However, plantCrystals containing extracellular vesicles (PCEVs) were formed during the preparation of plantCrystals through bead milling. Curcumin was either added after PCEVs were formed, resulting in curcumin-added PCEVs, or added to the soybean dispersion before bead milling, forming curcumin-loaded PCEVs. The formulations were characterized for their physicochemical properties and assessed for dermal penetration efficacy using quantitative dermatokinetic and semi-quantitative ex vivo porcine ear models. The results indicated that curcumin-loaded PCEVs achieved higher penetration efficacy compared to curcumin-added PCEVs and curcumin-loaded EVs, with approximately 1.5-fold and 2.7-fold increases in penetration efficacy, respectively. Additionally, curcumin-loaded PCEVs showed superior penetration depth, while curcumin from the curcumin-loaded EVs remained in the stratum corneum. These findings suggest that the plantCrystals strategy via bead milling offers a more effective approach than the classical EVs strategy for improving the topical delivery of class IV drugs like curcumin. Full article

Marine microalgae are emerging as promising sources of polyphenols, renowned for their health-promoting benefits. Recovering polyphenols from microalgae requires suitable treatment and extraction techniques to ensure their release from the biomass and analytical methodologies to assess their efficiency. This review provides a comprehensive comparison of traditional and cutting-edge extraction and analytical procedures applied for polyphenolic characterization in marine microalgae over the past 26 years, with a unique perspective on optimizing their recovery and identification. It addresses (I) cell disruption techniques, including bead milling, high-speed homogenization, pulsed electric field, ultrasonication, microwave, freeze-thawing, and enzymatic/chemical hydrolysis; (II) extraction techniques, such as solid–liquid extraction, ultrasound and microwave-assisted extraction, pressurized-liquid extraction, and supercritical CO₂; (III) analytical methods, including total phenolic and flavonoid content assays and advanced chromatographic techniques like GC-MS, HPLC-DAD, and HPLC-MS. Key findings showed bead milling and chemical hydrolysis as effective cell disruption techniques, pressurized-liquid extraction and microwave-assisted extraction as promising efficient extraction methods, and HPLC-MS as the finest alternative for precise phenolic characterization. Unlike previous reviews, this study uniquely integrates both extractive and analytical approaches in one work, focusing exclusively on marine microalgae, a relatively underexplored area compared to freshwater species, offering actionable insights to guide future research and industrial applications. Full article

The main objective of this research is to conduct an experimental investigation of the bimetallic material formed by 316LSI stainless steel and S275JR structural steel, produced via hybrid wire arc additive manufacturing technology with cool metal transfer welding and machining, and with the objective of being able to reduce the industrial cost of certain requirements for one of the materials. A methodological investigation has been carried out starting with welding beads of 316LSI on S275JR plates, followed by overlapping five beads and conducting final experiments with several vertical layers, with or without intermediate face milling. The results achieved optimal bead conditions for wire speeds of 4 m/min and 5 m/min at a travel speed of 400 mm/min. Overlap experiments show that the best deposition results are obtained with an overlap equal to or greater than 28%. Cooling time does not significantly influence the final geometry of the coatings. Regarding metallographic analysis, the filler material presents an austenitic columnar structure. In the base material, a bainitic structure with inferred grain refinement was detected in the heat-affected zone. An increase in hardness is observed in the heat-affected zone. In the results obtained from the tensile tests of the bimetallic material, an increase in mechanical strength and yield strength is observed in the tested specimens. Full article

The aim of the study is to formulate an injectable nanocrystalline suspension (NS) of dutasteride (DTS), a hydrophobic 5α-reductase inhibitor used to treat benign prostatic hyperplasia and scalp hair loss, for parenteral long-acting delivery. A DTS-loaded NS (DTS-NS, 40 mg/mL DTS) was prepared using a lab-scale bead-milling technique. The optimized DTS-NS prepared using Tween 80 (0.5% w/v) as a nano-suspending agent, was characterized as follows: rod/rectangular shape; particle size of 324 nm; zeta potential of −11 mV; and decreased drug crystallinity compared with intact drug powder. The DTS-NS exhibited a markedly protracted drug concentration-time profile following intramuscular injection, reaching a maximum concentration after 8.40 days, with an elimination half-life of 9.94 days in rats. Histopathological observations revealed a granulomatous inflammatory response at the injection site 7 days after intramuscular administration, which significantly subsided by day 14 and showed minimal inflammation by day 28. These findings suggest that the nanosuspension system is a promising approach for the sustained release parenteral DTS delivery, with a protracted pharmacokinetic profile and tolerable local inflammation. Full article

Microplastics (MPs) are persistent, globally relevant pollutants that have thus far been rigorously studied in natural waters but have not been as extensively studied in industrial wastewaters. Samples were collected from the forestry industry, wastewater treatment plants and the biogas industry. An enzymatic treatment protocol for MPs’ detection was applied to an assortment of industrial samples ranging from wastewaters, effluents and condensates to sludges and digestates. The effects of selected enzymes were studied systematically to develop a basis for digestion protocols on industrial samples. Further, different methods of detection (micro FTIR and Raman) were compared to each other, and the samples were visually examined using SEM. The developed protocols in this study were then compared with blank samples, contamination controls and samples spiked with artificial microplastics. This research aimed to fill some of the gap in the knowledge regarding the analysis methods and especially in the type of samples screened for microplastics thus far and presents a systematic approach to MPs’ detection in industrial wastewaters. It highlights the issues with the used analytical methods (such as misidentification) and validates the analysis results with milled, random shape and wide-size-range reference MPs that represent real samples better than standardized, ideal round beads. This study provides the first-ever suggestion for an enzymatic digestion protocol for industrial sample analysis. Full article

Microalgae are a promising biomass source because of their capability to fixate CO₂ very efficiently. In this study, the potential of Microchloropsis salina biomass as a feedstock for fermentation was explored, focusing on biomass hydrolysis by employing various mechanical and chemical cell disruption strategies in combination with enzymatic hydrolysis. Among the mechanical cell disruption methods investigated on a lab scale, namely ultrasonication, bead milling, and high-pressure homogenization, the most effective was bead milling using stainless-steel beads with a diameter of 2 mm. In this way, 87–97% of the cells were disrupted in 40 min using a mixer mill. High-pressure homogenization was also effective, achieving 86% disruption efficiency after four passes on a 30–200 L scale using biomass with 15% (w/w) solids content. Enzymatic hydrolysis of the disrupted cells using a mixture of cellulases and mannanases yielded up to 25% saccharification efficiency after 72 h. Acidic hydrolysis of undisrupted cells followed by enzymatic treatment yielded around 30% saccharification efficiency but was coupled with significant dilution of the resulting hydrolysate. Microalgal biomass hydrolysate produced was determined to have ~8.1 g L⁻¹ sugars and 2.5% (w/w) total carbon, as well as sufficient nitrogen and phosphorus content as a fermentation medium. Full article

This review details the extraction, characterization and utilization of seaweed-derived biopolymers for future packaging applications. The review is contextualized within the broader scope of the challenge of plastic pollution and the current urgent need for more sustainable packaging materials. Macroalgae (or seaweed) has been highlighted as a promising source of biopolymers, most commonly sodium alginate, agar and carrageenan, for reasons such as a rapid growth rate and decreased environmental impact when compared with terrestrial plant life. Extraction methods detailed include traditional solvent-based extraction and more sustainable developments such as ultrasound-assisted extraction, microwave-assisted extraction and bead milling. This review additionally presents the characterization techniques most pertinent in determining the applicability of these biopolymers in packaging applications. Properties of key importance to the development of sustainable packaging materials such as thermal properties, mechanical strength, barrier properties and biodegradability are highlighted in comparison to conventional petroleum-based plastics. This review concludes by realistically identifying the challenges faced by implementing seaweed-based biopolymers into packaging structures, such as cost-effectiveness, scalability and performance while suggesting future directions to mitigate these issues and improve the commercial viability of these materials for the packaging industry. Full article

This study aimed to develop a practical semi-mechanistic modeling framework to predict particle size evolution during wet bead milling of pharmaceutical nanosuspensions over a wide range of process conditions and milling scales. The model incorporates process parameters, formulation parameters, and equipment-specific parameters such as rotor speed, bead type, bead size, bead loading, active pharmaceutical ingredient (API) mass, temperature, API loading, maximum bead volume, blade diameter, distance between blade and wall, and an efficiency parameter. The characteristic particle size quantiles, i.e., x₁₀, x₅₀, and x₉₀, were transformed to obtain a linear relationship with time, while the general functional form of the apparent breakage rate constant of this relationship was derived based on three models with different complexity levels. Model A, the most complex and general model, was derived directly from microhydrodynamics. Model B is a simpler model based on a power-law function of process parameters. Model C is the simplest model, which is the pre-calibrated version of Model B based on data collected from different mills across scales, formulations, and drug products. Being simple and computationally convenient, Model C is expected to reduce the amount of experimentation needed to develop and optimize the wet bead milling process and streamline scale-up and/or scale-out. Full article

Abrasive waterjet (AWJ) machining offers the possibility of creating a wide range of features on mechanical parts with different degrees of complexity with a relatively high efficiency. However, after the roughing passes, the surface quality of features such as blind pockets is rather low, with unfavorable implications for surface waviness and form deviations apart from high surface roughness. Apart from the traditional methods for finishing, such as grinding or lapping, it is worth attempting either to improve the surface quality obtained during roughing by an AWJ or to integrate a post-processing step by using a pure WJ in the existing process in order to ameliorate the surface quality. Thus, in the current study, the effect of pure waterjet (WJ) post-processing of machined pockets by AWJ milling on a Ti-6Al-4V workpiece using recycled glass beads was investigated under different conditions. The findings indicate that although the different post-processing treatments by a pure WJ can affect the surface quality on average, these differences are not considerably important, probably due to an insufficient capability of material removal, which hinders the smoothing effect on machined surfaces. Thus, it was indicated that a higher number of post-processing passes under different conditions than those of the roughing pass can be more favorable for efficient post-treatment by a pure WJ. Full article

The use of nanoparticles (NPs) in industrial applications is consistently increasing given their peculiar properties compared to bulk precursor materials. As a result, there is a growing need to develop alternative technical strategies for the synthesis of such NPs using processes that are not only environmentally friendly but also easy and inexpensive to implement on an industrial scale. In this regard, a novel approach has recently been proposed for the safe and sustainable production of metal NPs directly from a bulky solid by magnetically driven low-energy wet milling, which overcomes the limits of applicability to ferromagnetic materials through a unique device configuration. In the present contribution, the understanding of this alternative configuration is deepened by computational investigation. Discrete Element Method (DEM) simulations were used to model the dynamics of the system, highlighting the role of the various parameters involved in the setup and operation of the process. The collisions between grinding and primary particles are analyzed in terms of frequency, impact angle, and energy. Comparing the results with the standard device configuration, the general trend is preserved, though collisions at higher impact angle and energy are also detected. Full article