Search Results (308)

Background/Objectives: Hot-melt injection molding (HMIM) was evaluated as a solvent-free process for the preparation of glibenclamide (GLB), a poorly soluble BCS Class II drug, glassy solutions with the objective of improving dissolution and bioavailability for diabetes. Methods: GLB was blended at a concentration of 10% w/w with PVP K25, PVP VA64, and Soluplus^® (SOL) matrices. The miscibility of the GLB–polymer systems (matrices) was calculated based on the Hansen solubility parameters and validated using differential scanning calorimetry (DSC) analysis. The HMIM extrudates were milled into granules and analysed for their solid-state properties (DSC, XRPD, FTIR, and SEM studies), and flow properties. The produced granules were compressed into immediate release tablets and assessed for in vitro performance, stability, and in vivo bioavailability using 20 healthy male Sprague Dawley rats. Results: Findings revealed the formation of single-phase glassy solutions, specifically for PVP VA64 and SOL, which also exhibited advantageous manufacturing and extrudate clarity. The glassy solution formulations showed considerably improved dissolution characteristics compared with the crystalline GLB and the commercial product. The glassy solution formulations displayed fast drug release for PVP K25 and PVP VA64, and biphasic drug release for SOL. Stability testing confirmed the capability of PVP VA64 and SOL to maintain GLB in a molecularly dispersed, amorphous state for 12 months. The in vivo assessment revealed an increase in relative bioavailability to 246.3% and 124.5% for the SOL and PVP VA64 formulations when compared to the commercial formulation. Conclusions: Overall, the findings demonstrate the potential of HMIM-processed glassy solutions, especially those prepared using SOL, as promising platforms for promoting oral delivery of the poorly soluble antidiabetic GLB. Full article

Background: Bedside manipulation of adult anti-tuberculosis tablets for paediatric dosing is common in low-resource settings, yet it can compromise drug stability. This study investigated how grinding and multi-drug co-suspension affect the supramolecular organisation, thermal stability, and dissolution of isoniazid (INH). Methods: INH raw, INH branded tablets (whole and ground), and multi-drug combination mixtures (MCMs) that simulate paediatric multi-drug-resistant tuberculosis (MDR-TB) regimens were assessed. Samples were analysed as solids and aqueous suspensions using hot-stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, FTIR-ATR, USP dissolution, and HPLC (LOD 0.0015 mg mL⁻¹; LOQ 0.005 mg mL⁻¹). Results: Grinding and co-mixing lowered melting points and masked typical INH events. Spectroscopy revealed the broadening and shifting of OH/NH and pyridine-ring bands, consistent with the formation of new hydrogen-bonding networks, correlative with supramolecular rearrangements. In multi-drug suspensions, INH fell below the HPLC quantification limit in both pH 1.2 and 6.8 media, despite visible residue, suggesting the formation of non-dissociable supramolecular complexes. Using a validated HPLC assay, no quantifiable INH was detected from the crushed multi-drug suspensions in either pH 1.2 or pH 6.8, whereas intact API/tablets showed measurable release. Conclusions: Co-suspension of INH with companion tuberculosis (TB) drugs disrupts its supramolecular integrity, leading to pre-administration degradation and a loss of quantifiable drug. Dissolution testing showed minimal INH release at pH 1.2 and none at pH 6.8, contrasting with intact tablets/API. These observations highlight that converting an immediate-release tablet into an aqueous suspension fundamentally alters its physicochemical environment and requires rational formulation design to preserve molecular stability, differentiating true resistance from formulation failure. Full article

The aim of this review is to analyze current routes for the administration and absorption of vitamin B12 in older adults, with a special focus on the sublingual route using orodispersible films, and evaluate the advances, materials, and challenges associated with this method of administration. Thus, the review aims to provide an updated overview of safe and effective alternatives for preventing and treating vitamin B12 deficiency in this age group. Vitamin B12 deficiency predominantly affects older adults. After the age of 70, absorption decreases, and deficiency occurs most frequently due to age-related gastric atrophy, decreased gastric acid production, reduced intrinsic factor secretion, and inadequate dietary vitamin B12 intake. This narrative review examines traditional and current treatments for vitamin B12 administration in older adults, with a focus on sublingual administration (SL) via orodispersible films (ODFs) to enhance absorption, adherence, and accessibility. SL vitamin B12 bioavailability, advantages versus disadvantages, ODF formulations (polymers such as pregelatinized starch, HPMC, and chitosan), and pharmaceutical process challenges (solvent casting and hot-melt extrusion) were explored in the reviewed in vitro and in vivo studies. According to the collected evidence, the sublingual route appears to offer rapid absorption directly into the bloodstream, with efficacy comparable to/superior to intramuscular (IM)/oral (OP) routes of administration, representing a patient-centered innovation for older adults that overcomes painful treatments and gastrointestinal/swallowing barriers. Future longitudinal clinical trials should validate long-term efficacy, standardize materials, and scale up to viable industrial production, addressing issues related to chemical stability and polypharmacy. Full article

Background/Objectives: Poor aqueous solubility of active pharmaceutical ingredients (APIs) remains a critical barrier to effective oral formulation. This study investigated the production of ketoprofen amorphous solid dispersions (ASDs) via hot melt extrusion (HME) using hydrophilic carriers and surfactants to enhance solubility and dissolution. Methods: ASDs were prepared by the fusion method employing mannitol or polyethylene glycol (PEG) 4000 hydrophilic carriers and further modified by addition of poloxamer 188 or poloxamer 407 as surfactants. Solubility was evaluated, and the best performing formulations were selected for HME to assess the effect of extrusion parameters (temperature, screw speed and re-extrusion) on API solubility and dissolution. Selected ASD extrudates were formulated into tablets and capsules and further tested. Results: Ternary ASDs exhibited higher solubility than their binary counterparts. The combinations of high-concentration hydrophilic carrier (mannitol or PEG 4000) and poloxamer 407 proved the most effective. The HME-produced ASDs showed superior solubility compared to the simple fusion method, with temperature being the most critical processing parameter, while screw speed and re-extrusion were carrier dependent, enhancing solubility for mannitol-based ASDs but not for PEG 4000; re-extrusion also led to mild color changes and technological issues preventing further processing. The selected ASD extrudates were successfully formulated into tablets and capsules with good physical characteristics and dissolution profiles. Conclusions: These findings demonstrate the need to further investigate the potential of re-extrusion strategies and surfactant-enhanced ASD systems for improving the oral delivery of poorly soluble drugs. Full article

Background/Objectives: Oral surgical procedures in patients at risk of/diagnosed with MRONJ require systemic antibiotic therapy, which can fail to achieve an adequate local drug concentration. This research aims to design mucoadhesive buccal patches (containing erythromycin or the erythromycin–resveratrol combination) tailored to the therapeutic needs of patients at risk of MRONJ undergoing oral surgery. Methods: Erythromycin (ERY) and resveratrol (RSV) were embedded into lipid-based microparticles prepared via hot melt dispersion. The microparticles, recovered in the form of dry powders, were characterized in terms of yield, softening/melting temperature, active(s) content, physical state (amorphous vs. crystalline), and individual and bulk properties. Then, they were loaded into a hydrophilic gel, which was dried, obtaining microparticle-loaded buccal patches. The optimized patches were characterized in terms of uniformity, folding endurance, swelling, mucoadhesion, and oromucosal permeation/retention. Results: The microparticles were efficiently produced via a green approach, resulting in reproducible pharmaceutical powders with high loading efficacy (≈90%), spherical morphology, particle sizes in the range of approximately 106–425 μm, and a softening temperature close to body temperature. The buccal patches were also obtained via a green approach, and were found to be thin, flexible, homogeneous, highly swellable, extremely mucoadhesive, and able to promote ERY and RSV accumulation in the buccal tissue (≈25% and 2% of ERY and RSV, respectively, after 2 h) while avoiding active(s) absorption. Conclusions: The proposed buccal patches are viable candidates for further clinical trials aimed at evaluating both the effectiveness of locoregional antibiotic treatment and the usefulness of the co-administration of RSV and ERY. Full article

Background: Three-dimensional (3D) printing has been established in pharmaceutical sciences for preparing customized dosage forms with intricate release profiles. However, realizing this potential requires complex design strategies and the careful use of various excipients. This study was designed to evaluate the utility of hypromellose acetate succinate (HPMC-AS) as a singular release-modifying excipient for manufacturing oral solid dosage forms via fused deposition modeling (FDM) 3D printing. Methods: The scope of work encompassed comprehensive material characterization, formulation and production of drug-loaded filaments using hot-melt extrusion (HME), subsequent FDM 3D printing of tablet geometries, and in vitro dissolution studies using mebeverine hydrochloride (MebH) as the model drug. Results: Initial HME processing indicated that the HPMC-AS-based filaments were brittle, presenting technical challenges for direct 3D printing. This issue was successfully overcome by incorporating an additional preheating stage into the FDM printing process, which enabled production of the tablets. Dissolution analysis demonstrated that the 3D-printed mebeverine hydrochloride tablets exhibited delayed and sustained-release characteristics. Conclusions: These results confirm the viability of HPMC-AS as a standalone functional excipient in FDM 3D printing to produce tailored, complex drug delivery systems. Full article

In aerospace, defense, and energy systems, ceramic matrix composites (CMCs) are smart structural materials designed to function continuously in harsh mechanical, thermal, and oxidative conditions. Using high-strength fiber reinforcements and tailored interphases that enable damage-tolerant behavior, their creation tackles the intrinsic brittleness and low fracture toughness of monolithic ceramics. With a focus on chemical vapor infiltration, polymer infiltration and pyrolysis, melt infiltration, and additive manufacturing, this paper critically analyzes current developments in microstructural design, processing technologies, and interfacial engineering. Toughening mechanisms are examined in connection to multiscale mechanical responses, including controlled debonding, fiber bridging, fracture deflection, and energy dissipation pathways. Cutting-edge environmental barrier coatings are assessed alongside environmental durability issues like oxidation, volatilization, and hot corrosion. High-performance braking, nuclear systems, hypersonic vehicles, and turbine propulsion are evaluated as emerging uses. Future directions emphasize self-healing systems, ultra-high-temperature design, and environmentally friendly production methods. Full article

Background: Three-dimensional printing (3DP) is a promising technology for advancing pharmaceutical research by enabling the production of personalized drug products. However, its progress has been hindered by the conventional trial-and-error approach to excipient selection and optimization. Methods: In this study, the blend module was employed to determine the miscibility parameters—mixing energy (E_mix) and Flory–Huggins interaction parameter (χ) to find the right excipients and drug–excipient ratio and examine the incorporation of plasticizers and lipids to enhance printability. Furthermore, molecular dynamics (MD) simulations were employed to calculate the cohesive energy density (CED) for predicting the dissolution behavior of 3DP formulations. Results: Data from 51 formulations were analyzed, enabling correlation and experimental validation of the in silico predictions. The predicted miscibility values demonstrated a strong correlation with experimental printability results. Furthermore, using a miscibility parameter, it was possible to accurately forecast minor changes in the drug-to-excipient ratio, plasticizer/lipid concentration, and hot-melt extrusion (HME) temperature that affect printability. Hydrophilic carriers exhibited lower CED values corresponding to faster drug release. In contrast, more hydrophobic carriers revealed high CED values, indicating stronger drug entrapment and sustained release. Conclusions: The miscibility parameters and MD-simulated CED values provide a practical framework for early-stage, high-throughput excipient screening. Overall, in silico prediction offers a viable strategy for modeling the entire 3DP workflow, minimizing the need for trial-and-error experimentation, and thereby accelerating the clinical translation of 3DP drug delivery systems. Full article

This study presents a comparative analysis of two industrially relevant technologies for manufacturing of prepreg composite materials based on polyimide (PI) resin: hot-melt and solvent-based technology. More specifically, the study focuses on evaluating the relationship between key processing parameters and the final properties of the composite material manufactured with unidirectional (UD) C-fibers and woven fabrics used as reinforcement for both technologies. The impregnation process was carried out using a custom-designed coating equipment developed by Mikrosam D.O.O. Manufactured prepregs were characterized in terms of their resin content, volatile content, weight, width, and quality of the applied resin film. The hot-melt method that involves applying the resin in a semi-molten state with minimal solvent content provided a stable resin content (34–35%) and low volatiles (~1.2–1.5%) in the final product. The solvent-based method, using a resin/solvent ratio of 50:50, enabled deeper resin penetration into the fibers, particularly in woven fabrics (resin content: 34–37%) and lower residual volatiles (~0.3–0.5%). These results showed that the hot-melt technology consistently produced prepregs with very stable resin content, which is critical for structural applications requiring increased mechanical performance. In contrast, the solvent-based method demonstrated better adaptability to different reinforcement forms, improved impregnation depth, and excellent film uniformity, particularly suitable for woven fabrics. Representative SEM micrographs confirmed uniform resin distribution, full fiber wetting, and absence of voids, validating the impregnation quality obtained by both techniques. These findings highlight the technological relevance of selecting the appropriate impregnation route for each reinforcement architecture, offering direct guidance for industrial-scale composite manufacturing, where the hot-melt method is preferred for UD prepregs requiring precise resin control, while solvent-based impregnation ensures deeper and uniform resin distribution in woven fabric structures. Full article

A microalloyed (MA) steel, combined with titanium diboride (TiB₂), was utilised to create a unique steel matrix composite (SMC), enhancing the modulus of the MA steel while also improving its strength. Through thermomechanical processing stages, including hot rolling and plane-strain compression (PSC) testing, followed by various final cooling methods, a cooling rate of 0.1 °C/s was identified as the most effective for achieving a ferrite–pearlite microstructure, which is suitable for toughness and ductility. With TiB₂ reinforcement successfully incorporated via Fe-Ti and Fe-B additions during vacuum induction melting (VIM), it was observed that the TiB₂ particles were homogeneously dispersed in both 5% and 7.5% nominal volume fraction additions, exhibiting faceted and hexagonal morphology. TiB₂ was found to exert a grain-pinning effect on recrystallised austenite at 1050 °C, as evidenced by the retention of grain orientation from hot rolling, in contrast to the MA steel deformed without the composite reinforcement. Increasing the volume fraction of TiB₂ improved the stiffness and strength of both composite alloys, verified through mechanical testing. Full article

Tungsten is a prime candidate material for the plasma-facing components of fusion reactors, thanks to its high melting point, high temperature strength, good thermal conductivity, high erosion resistance, etc. Yet, it has some limitations, mainly its brittle nature, difficulty of machining, and propensity to recrystallize at elevated temperatures. Among the approaches to the improvement of particular properties are alloying, dispersion strengthening, thermomechanical processing, and modifications to the sintering process. This study explores the possibility of combining fine powder size with ultra-high pressure to achieve significant densification at moderate temperatures during hot pressing. Two powder sizes and a range of temperatures from 1000 to 2000 °C were used, and their effects were observed. The resulting tungsten compacts were characterized for their microstructure, density, and mechanical and thermal properties. The high pressure enabled substantial densification already at relatively low temperatures, thanks to the plastic deformation of the powder particles. A significant degree of sintering, as manifested by the microstructural and property evolution, occurred however only at higher temperatures. The compacts exhibited brittleness, calling for further optimization of the method. Full article

Background: Lycopene is a powerful antioxidant, classified as a carotenoid. Numerous studies confirm its beneficial effects in both the prevention and treatment of various diseases. However, its therapeutic application is significantly limited due to its poor water solubility and low bioavailability from natural sources. Developing a formulation with improved therapeutic characteristics could enhance the effectiveness of lycopene, making it more suitable for medical and nutritional use. The objective of this work was to apply hot-melt extrusion to produce extrudates containing an acetone-based lycopene extract combined with selected polymers, aiming to enhance its dissolution properties. Methods: Lycopene-rich extracts were prepared using ultrasound-assisted extraction with acetone. The obtained extract was processed via hot-melt extrusion together with PVP VA64 and Soluplus. The resulting extrudates were characterized using attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Dissolution behavior was assessed using a paddle apparatus, and collected samples were quantified by HPLC. Antioxidant capacity was determined via DPPH radical-scavenging analysis. Results: The polymers PVP VA64 and Soluplus improve lycopene’s dissolution in acidic environments while showing its antioxidant potential. Conclusions: The formulation combining lycopene obtained through hot-melt extrusion with PVP VA64 and Soluplus polymers will enable its wider and more effective application. Full article

Background/Objectives: Fused deposition modeling (FDM) three-dimensional (3D) printing represents an emerging manufacturing platform for personalized oral dosage forms. Its success relies on developing robust drug-loaded filaments with consistent mechanical, thermal, and dissolution properties. This work aims to (i) develop and characterize ketoprofen-loaded filaments using hot-melt extrusion (HME) and (ii) utilize them to fabricate both immediate-release (IR) and sustained-release (SR) tablets via FDM 3D printing. Methods: Filaments were prepared using Kollicoat^® IR and hydroxypropyl methylcellulose (HPMC, 2600–5600 cP) as functional polymers. Sorbitol and sodium lauryl sulfate (SLS) were incorporated as plasticizer and surfactant, respectively. Filaments were evaluated for quality attributes, drug content, tensile strength, and physicochemical and surface characteristics using Scanning Electron Microscopy (SEM), Attenuated Total Reflection Fourier-transform infrared (ATR-FTIR), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Optimized filaments were fed into an FDM 3D printer to fabricate ketoprofen tablets with varied geometries, shell numbers, and infill densities. Tablets were subjected to USP tests (weight variation, friability, hardness, disintegration, assay, content uniformity), dissolution profiling, and release kinetics modeling. Comparative dissolution studies with market Profenid^® and Bi-Profenid^® tablets were conducted. GastroPlus^® simulations were used for in vitro–in silico correlation. Results: Among the tested formulations, Kollicoat^® IR-based filaments with sorbitol and SLS (F6) demonstrated superior printability, characterized by consistent feeding, stable extrusion, and reliable formation of uniform structures for immediate-release applications. In contrast, HPMC-based filaments with sorbitol (F13) offered the most robust performance for SR formulations. Both exhibited uniform diameter, drug loading, and mechanical strength. IR tablets achieved >80% release within 30 min, while SR tablets prolonged release up to 12 h, following Higuchi and Korsmeyer–Peppas kinetics. All quality attributes complied with USP limits. Market products showed comparable dissolution, validating the approach. GastroPlus^® simulations predicted pharmacokinetic profiles consistent with reported data, supporting IVIVC. Conclusions: This integrated workflow establishes a robust strategy for producing IR and SR ketoprofen tablets from a single FDM platform. The results highlight the feasibility of point-of-care, personalized medicine using 3D printing technologies. Full article

Integrating phase change materials (PCMs) into buildings and HVAC systems improves thermal comfort and energy efficiency. This study presents a climate-responsive methodology for selecting optimal PCMs using a multi-criteria decision-making (MCDM) framework. AHP was employed to determine the relative importance of key thermophysical properties, including melting point (47.5%), latent heat of fusion (25.7%), volumetric latent heat (13.5%), thermal conductivity (6.8%), specific heat capacity (3.3%), and density (3.3%). These weights were applied across five MCDM techniques—COPRAS, VIKOR, TOPSIS, MOORA, and PROMETHEE II—to evaluate 16 PCM alternatives for three representative climate zones: temperate (18 °C), subtropical (23 °C), and tropical hot/desert (28 °C). The results consistently identified n-Heptadecane (C17) as the most suitable PCM for temperate and subtropical climates, while n-Octadecane (C18) and hydrated salts such as CaCl₂·6H₂O and Na₂CO₃·10H₂O were optimal for tropical zones. Results show that n-Heptadecane (C17) is optimal for temperate and subtropical zones (COPRAS K = 1.00; TOPSIS C = 0.79–0.82; PROMETHEE φ = 0.21–0.22), while n-Octadecane (C18) and hydrated salts such as CaCl₂·6H₂O and Na₂CO₃·10H₂O perform best in tropical climates (TOPSIS C = 0.85; PROMETHEE φ = 0.26). These PCMs offer high latent heat (up to 254 kJ·kg⁻¹) and volumetric storage (up to 381 MJ·m⁻³), enabling significant reductions in HVAC loads and improved indoor temperature stability. The convergence of rankings across methods and alignment with existing literature validate the robustness of the proposed approach. This framework supports informed material selection for sustainable building design and can be adapted to other climate-sensitive engineering applications. The framework introduces methodological innovations by explicitly mapping PCM melting points to climate-specific comfort bands, incorporating volumetric latent heat, and validating rankings through cross-method convergence (Spearman ρ > 0.99). Sensitivity analysis confirms robustness against weight perturbations. The approach supports practical PCM selection for both new and retrofit buildings, contributing to EU and US energy goals (e.g., 40% building energy use, DOE’s 50% reduction target). Full article

This study investigated the microstructure and corrosion behavior of 30MnB5 hot-stamped steel after applying a zinc coating using the cold-spraying method followed by heat treatment (HT). Al-10 wt%Si coating is essential for improving the high-temperature corrosion resistance of 30MnB5 steel during the hot-stamping process. Before HT, the coating layer primarily consisted of Al, whereas after HT, Fe–Al-based intermetallic compounds were formed throughout the layer. The Zn in the coating layer applied using the cold-spraying method was not uniformly distributed before HT. However, during HT, the low-melting-point Zn melted and re-solidified, allowing it to combine with Fe diffusing from the substrate. Consequently, Zn–Al–Fe-based intermetallic compounds were formed on the surface of the coating layer. In the Zn-coated specimens, the current density near the corrosion potential tends to be lower than that of the Al–Si-coated specimens because Zn corrodes preferentially owing to its sacrificial anode effect, thereby protecting the underlying Al–Si-coated layer and steel. Full article