Search Results (565)

Background: The limited aqueous solubility of BCS Class II drugs, exemplified by itraconazole (ITR), continues to hinder their bioavailability and therapeutic performance following oral administration. The present study investigated the development of amorphous solid dispersions (ASDs) of ITR via continuous manufacturing technologies, such as hot melt extrusion (HME) and spray drying (SD), to improve drug release. Methods: Polymer selection was guided by Hansen solubility parameter (HSP) analysis, film casting, and molecular modeling, leading to the identification of aminoalkyl methacrylate copolymer type A (Eudragit^® EPO), polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus^®), and hypromellose acetate succinate HG (AQOAT^® AS-HG) as suitable carriers. ASDs were prepared at drug-to-polymer ratios of 1:1, 1:2, and 2:1. Comprehensive characterization was performed using ATR-FTIR, NMR, DSC, PXRD, SEM, PLM, and contact angle analysis. Results: HME demonstrated higher process efficiency, solvent-free operation, and superior dissolution enhancement compared to SD. Optimized HME-based ASDs were formulated into tablets. The ITR–Eudragit^® EPO formulation achieved 95.88% drug release within 2 h (Weibull model, R² > 0.99), while Soluplus^® and AQOAT^® AS-HG systems achieved complete release, best described by the Peppas–Sahlin model. Molecular modeling confirmed favorable drug–polymer interactions, correlating with the formation of stable complex and enhanced release performance. Conclusions: HME-based continuous manufacturing provides a scalable and robust strategy for improving the oral delivery of poorly water-soluble drugs. Integrating predictive modeling with experimental screening enables the rational design of ASD formulations with optimized dissolution behavior, offering potential for improved therapeutic outcomes in BCS Class II drug delivery. Full article

This study focuses on realistic modeling of forming load and microstructural evolution during hot metal extrusion, emphasizing the effects of friction models and hydraulic press behavior. Rather than merely predicting load magnitudes, the objective is to replicate actual press operation by integrating a load limit response into finite element modeling (FEM). By applying Coulomb and shear friction models under both constant and hydraulically controlled press conditions, the resulting impact on grain size evolution during deformation is examined. The hydraulic press simulation features a maximum load threshold that dynamically reduces die velocity once the limit is reached, unlike constant presses that sustain velocity regardless of load. P91 steel is used as the material system, and the predicted grain size is validated against experimentally measured data. Incorporating hydraulic control into FEM improves the representativeness of simulation results for industrial-scale extrusion, enhancing microstructural prediction accuracy, and ensuring forming process reliability. Full article

To address the critical challenge of synergistically enhancing both high-temperature mechanical properties and thermal conductivity in neutron-absorbing materials for dry storage of spent nuclear fuel, this study proposes an innovative strategy. This approach involves the controlled distribution, size, and crystalline states of nano-Al₂O₃ within an aluminum matrix. By combining plastic deformation and heat treatment, we aim to achieve a structurally integrated functional design. A systematic investigation was conducted on the microstructural evolution of Al₂O₃/10 wt.% B₄C/Al composites in their forged, extruded, and heat-treated states. We also examined how these states affect high-temperature mechanical properties and thermal conductivity. The results indicate that applying hot extrusion deformation along with optimized heat treatment parameters (500 °C for 24 h) allows for a lamellar dispersion of nano-Al₂O₃ and a crystallographic transition from amorphous to γ-phase. As a result, the composite demonstrates a tensile strength of 144 MPa and an enhanced thermal conductivity of 181 W/(m·K) at 350 °C. These findings provide theoretical insights and technical support for ensuring the high density and long-term safety of spent fuel storage materials. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. 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

Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus^® and Kollidon^® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article

The burgeoning crisis of plastic waste accumulation necessitates innovative approaches towards sustainable packaging solutions. Polylactic acid (PLA), a leading biopolymer, emerges as a promising candidate in this realm, especially for environmentally friendly packaging. PLA is renowned for its compostable properties, offering a strategic avenue to mitigate plastic waste. However, its dependency on specific industrial composting conditions, characterized by elevated temperatures, humidity, and thermophilic microbes, limits its utility for household composting. This study aims to bridge the research gap in PLA’s recyclability and explore its feasibility in mechanical recycling processes. The research focuses on assessing the mechanical characteristics of PLA and PLA-based composites post-recycling. Specifically, we examined the effects of two extrusion methods—conical and parallel—on PLA and its composites containing 20 wt.% basalt fibers (BF). The recycling process encompassed repeated cycles of hot melt extrusion (HME), followed by mechanical grinding to produce granules. These granules were then subjected to injection moulding (IM) after 1, 3 and 5 recycling cycles. The tensile properties of the resulting IM-produced bars provided insights into the material’s durability and stability. The findings reveal that both PLA and PLA/BF composites retain their mechanical integrity through up to 5 cycles of mechanical recycling. This resilience underscores PLA’s potential for integration into existing recycling streams, addressing the dual challenges of environmental sustainability and waste management. The study contributes to the broader understanding of PLA’s lifecycle and opens new possibilities for its application in eco-friendly packaging, beyond the limits of composting. The implications of these findings extend towards enhancing the circularity of biopolymers and reducing the environmental footprint of plastic packaging. Full article

The objective of the current research is to investigate the role of Neusilin US2 as a porous carrier for improving the drug loading and stability of Ezetimibe (EZB) by hot melt extrusion (HME). The amorphous solid dispersions (ASDs) were developed from 10–40% of drug loading using Kollidon VA 64 (Copovidone) as a polymer matrix and Neusilin US2 as a porous carrier. The solid-state characterization of EZB was studied using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). The formulation blends were characterized for flow properties, and CTC (compressibility, tabletability, compactibility) profile. The in-vitro drug release profiles were studied in 0.1 N HCl (pH 1.2). The incorporation of Neusilin US2 has facilitated the development of ASDs up to 40% of drug loading. The CTC profile has demonstrated excellent tabletability for the ternary (EZB, copovidone and Neusilin) dispersions over binary dispersion (EZB and copovidone) formulations. The tablet formulations with binary (20%) and ternary (30% and 40%) dispersions have demonstrated complete dissolution of the drug in 30 min in 0.1 N HCl (pH 1.2). The incorporation of copovidone has prevented the recrystallization of the drug in the solution state. Upon storage of formulations at accelerated conditions, the stability of ternary dispersion tablets was preserved attributing to the entrapment of the drug within Neusilin pores thereby inhibiting molecular mobility. Based on the observations, the current research concludes that it is feasible to incorporate Neusilin US2 to improve the drug loading and stability of ASD systems. Full article

Precision extrusion forging is an innovative manufacturing process for trouble-free production of high-quality components with an accurate shape. The process provides a reduced technological chain and high production efficiency, as only certain surfaces need additional processing. This study used QForm software as an environment for simulating precision extrusion forging. The main goal of this research was to present a brief overview of the latest research on the simulation of precision extrusion forging, with an emphasis on the production cycle rather than on mathematical description. This article examines the processes of simulation modeling of precision extrusion forging with newly designed tooling for the manufacture of a newly introduced asymmetric load-bearing facade element patented by Braykov. With the help of simulation modeling, appropriate modes for specific production were established, and were later implemented. The production process itself is briefly presented at the end of this article. Full article

Thermokinetic characterization of amorphous carbamazepine was performed utilizing non-isothermal differential scanning calorimetry (DSC) and thermogravimetry (TGA). Structural relaxation of the amorphous matrix was described in terms of the Tool–Narayanaswamy–Moynihan model with the following parameters: Δh* ≈ 200–300 kJ·mol⁻¹, β = 0.57, x = 0.44. The crystallization of the amorphous phase was modeled using complex Šesták–Berggren kinetics, which incorporates temperature-dependent activation energy and degree of autocatalysis. The activation energy of the crystal growth was determined to be >320 kJ·mol⁻¹ at the glass transition temperature (T_g). Owing to such a high value, the amorphous carbamazepine is stable at T_g, allowing for extensive processing of the amorphous phase (e.g., self-healing of the quench-induced mechanical defects or internal stress). A discussion was conducted regarding the converse relation between the activation energies of relaxation and crystal growth, which is possibly responsible for the absence of sub-T_g crystal growth modes. The high-temperature thermal decomposition of carbamazepine proceeds via multistep kinetics, identically in both an inert and an oxidizing atmosphere. A complex reaction mechanism, consisting of a series of consecutive and competing reactions, was proposed to explain the second decomposition step, which exhibited a temporary mass increase. Whereas a negligible degree of carbamazepine degradation was predicted for the temperature characteristic of the pharmaceutical hot-melt extrusion (~150 °C), the degradation risk during the pharmaceutical 3D printing was calculated to be considerably higher (1–2% mass loss at temperatures 190–200 °C). Full article

Aim: In addition to numerous benefits provided by nanosuspensions (NSs) (e.g., enhanced saturation solubility, increased area for interaction with fluids), they suffer from major stability, handling and compliance issues. To overcome these challenges, we evaluated the feasibility of hot melt extrusion (HME) in transforming a cinnarizine-based NS, selected as a case study, into granules for oral intake. Methods: Thermoplastic polymers, in principle compatible with the thermal behavior of the selected drug and characterized by different interaction mechanisms with aqueous fluids, were used as carriers to absorb the NS and were processed by HME. Results: The extruded granules pointed out good physio-technological characteristics, a drug content > 85% with coefficient of variation (CV) < 5% and tunable in vitro performance coherent with the polymeric carriers they were composed of. Particle size as well as the solid state of cinnarizine was checked using several analytical techniques in combination (e.g., DSC, SEM, FT-IR, Raman). Depending on the composition of the granules, and specifically for formulations processed below 85 °C, the drug was found to remain crystalline and in the desired nanoscale. Conclusions: HME turned out to be a versatile process to transform, in a single-step, NSs into multi-particulate solid products for oral administration showing a variety of release profiles. Full article

The immiscibility of thermoplastic starch (TPS) and polybutylene succinate (PBS) complicates the thermal processing of these materials. This study provides the first comparative assessment of two compatibilizers with differing reaction mechanisms, Joncryl^® ADR 4468 and epoxidized linseed oil (ELO), for the optimization of biobased TPS/PBS blends. A total of 13 batches, varying in compatibilizer and blend composition, were processed via hot melt extrusion and injection molding to produce pellets. Blends were analyzed using tensile and impact testing, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), rheology, and scanning electron microscopy (SEM). The findings suggest that both compatibilizers can improve the compatibility of these blends, as evidenced by higher glass transition temperatures (T_g) compared to the reference batch (100-0-N/A). Joncryl^® ADR 4468 batches exhibit superior tensile strength and Young’s moduli, while ELO batches demonstrate greater elongation at break. The enhanced processability observed in Joncryl^® ADR 4468 is attributed to the increased polymer chain entanglement and molecular weight, whereas ELO facilitates greater chain mobility due to its plasticizing effect. These differences arise from the distinct mechanisms of action: Joncryl^® ADR 4468 promotes chain extension and crosslinking, whereas ELO mainly enhances flexibility through plasticization. Overall, this study provides a comparative assessment of these compatibilizers in TPS/PBS blends, laying the groundwork for future investigations into optimizing compatibilizer concentration and blend composition. Full article

As the severe environmental impacts of plastic pollution demand determined action, the European Union (EU) has included recycling at the core of its policies. Consequently, evolving jurisdiction now aims to achieve a recycling rate of 65% for non-PET plastic bottles by 2040. However, the widespread use of post-consumer high-density polyethylene (rPE-HD) recyclates in household chemical containers is still limited by PP contamination, poor mechanical properties, and low environmental stress cracking resistance (ESCR). Although previous studies have explored the improvement of regranulate properties through additives, few have examined whether reducing the variety of extrusion blow-moulded PE-HD packaging could offer similar benefits. Therefore, two sorted fractions of rPE-HD hollow bodies were processed into regranulates under industrial conditions, including hot washing, extrusion, and deodorisation. Subsequently, both materials underwent comprehensive characterisation regarding their composition and performance. The opaque material, which was sourced from milk bottles in the UK, exhibited greater homogeneity with minor impurities, leading to improved ductility and melt strain hardening at moderate strain rates compared to the mixed material stream, which contained approximately 2.5% PP contamination. However, both rPE-HD recyclates exhibited similar short-term creep behaviour, relatively low strain hardening moduli, and were almost devoid of inorganic particles. Considering the sum of the investigated properties, melt blending with suitable virgin material is likely one of the most effective options to maximise regranulate utilisation in hollow bodies, followed by recycling-oriented packaging design (e.g., for efficient sorting), and the employment of advanced sorting technology. Full article

Lollipop sticks were developed with fully biobased materials made of different plantain by-products, using extrusion processing followed by hot compression molding. The thermoplastic matrix was constituted of flour and starch from plantain bunch pulp and plantain peel cake. At the same time, two types of reinforcement were used, one of them being yarn from the lignocellulosic fibers of the pseudostem sheaths to constitute the BC1 lollipop stick and the other directly from the plantain pseudostem treated sheath to establish the BC2 lollipop stick. The biobased lollipop sticks were characterized in the migration test, finding a higher structural stability in lipophilic foods, with chocolate chosen as a confection to undergo physicochemical, structural, mechanical, and dynamic–mechanical characterization when interacting with the two biobased lollipop sticks until post-consumption was reached. The BC2 lollipop stick was characterized by maintaining higher stability in maximum tensile strength (12.62 to 11.76 MPa), higher flexural strength (19.07 to 10.11 MPa), storage modulus (4.97 to 1.65 GPa at 30 °C), and Tan delta (66.90 to 52.64 °C). Full article

This study compares the microstructures and mechanical properties of the AlSi10Mg alloy processed by laser powder bed fusion (LPBF) after undergoing different post-processing techniques. These techniques include conventional extrusion at 350 °C (CE-350) and KOBO extrusion at both room temperature (KOBO-RT) and 350 °C (KOBO-350). The extrusion processes, regardless of the method used, effectively densified the alloy, fragmented the primary silicon network, and refined the grain structure. Notably, a microstructure analysis indicated that the CE-350 method produced the finest grains, whereas the KOBO-350 method resulted in the largest grains. From a mechanical perspective, extrusion significantly increased ductility—rising from 2.4% to more than 14% elongation—while decreasing strength compared to the as-built state. Among the extruded samples, CE-350 provided the best balance of strength and ductility, exhibiting a yield strength of 186 MPa and a ductility of 18.1% elongation. Overall, the results demonstrate that while extrusion enhances ductility, it does so at the expense of strength, with conventional extrusion yielding a more favorable property balance for this alloy under the tested conditions. Full article