Search Results (143)

Background/Objectives. Warfarin possesses a bitter taste and requires a personalized dose in the range of 4.5 to 77 mg per week. This study investigated the potential for personalizing warfarin dosing by developing taste-masked matrix pellets. Pellets, supposedly, can be counted and orally administered in the required quantity to obtain the required dose. Methods. The study evaluated the effects of drug load (10, 20, and 30 wt.%) on the duration of thermal postprocessing (to achieve the desired aspect ratio) and drug release. The warfarin sodium clathrate was characterized by determining its pKa value and dissolution kinetics in water, stomach-simulated media (0.1 M HCl, pH 1.2), and mouth-simulated media (phosphate-buffered solution (PBS), pH 6.8). A solid dispersion of warfarin sodium clathrate with Kollicoat^® Smartseal 100 P or Eudragit^® E PO was prepared using hot melt extrusion (HME). The mechanical properties of extruded filaments were characterized by measuring their elastic modulus. The microparticles (1–4 mm in length) prepared with filament cut pelletizing were thermally treated to produce ‘smoothened’ particles, which were analyzed with optical microscopy and drug release testing. Conclusions. Microparticles with smoothened edges and an aspect ratio close to one are expected to improve mouthfeel and potentially patient compliance. No drug release was observed in mouth-simulated media, which indicated applicability to the taste masking of the microparticles. The proposed thermal treatment of HME microparticles, exemplified in this study, is a novel concept with underexplored potential in preparing taste-masked matrix pellets and dose personalization. Full article

This paper presents an analysis of the physicochemical and biological properties of the developed composite zinc phosphate cement modified with bismuth oxide and phosphorus slag additives. The powder phase was synthesized by sintering a frit with an optimal composition (ZnO, MgO, SiO₂, Bi₂O₃) using phosphorus slag as the active component. The study included an assessment of the microstructure, chemical resistance in aggressive environments (5% NaCl solution, 10% lactic acid, carbonated water), solubility in artificial saliva, and cytotoxicity in human fibroblasts. The addition of phosphorus slag was found to promote the formation of low-melting eutectics, which reduces the sintering temperature by 100 °C and increases the material’s whiteness to 97.8%. X-ray diffraction analysis confirmed the presence of zincite, quartz, and periclase phases, forming a dense microstructure without pronounced pores or cracks. The experimental cement demonstrated high acid resistance: the maximum weight loss in lactic acid was 8%, while the leaching of toxic elements (Pb, As, Cr, etc.) remained extremely low (10–67 ppm), confirming the material’s environmental safety. Testing of the composite zinc phosphate cement in artificial saliva revealed minimal weight loss compared to similar products. Biological testing showed that the cement’s cytotoxicity is dose-dependent; at a 0.3 g dose and a 1:4 dilution, the material loses its toxic properties and becomes safe for living tissue. The developed zinc phosphate composite cement composition offers improved aesthetic and mechanical properties, high chemical stability, and biocompatibility at working concentrations, making it promising for use in clinical dentistry. Full article

Background/Objectives: Amorphous solid dispersions (ASDs) produced via hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing represent a promising strategy for improving the performance of poorly water-soluble drugs. However, the integrated HME-FDM workflow is inherently energy-intensive, and sustainability considerations are rarely incorporated into formulation and process optimization. The present study aimed to develop and optimize indomethacin (IND) ASDs using a systematic Design of Experiment (DoE) framework that integrates electrical energy consumption as a quantitative response alongside pharmaceutical performance attributes. Methods: Polymer–plasticizer miscibility was screened using hot-stage microscopy, followed by filament preparation via HME. A factorial DoE was applied to optimize drug loading and extrusion temperature considering electrical energy consumption, extrusion yield, encapsulation efficiency, and residual crystallinity. Solid-state characterization was performed using DSC and XRD. The optimized filament was subsequently subjected to geometry screening and a second DoE to optimize platform temperature, nozzle temperature, and printing speed with respect to printing time, electrical energy consumption, and drug assay. Results: Complete drug amorphization was achieved within a defined thermal window, with residual crystallinity governed by kinetic dissolution constraints at lower extrusion temperatures. Electrical energy demand during both HME and FDM was strongly influenced by thermal setpoints and process duration. Multi-response overlay analysis identified sustainability-oriented operating windows for both stages. Experimental validation confirmed close agreement between predicted and observed responses, demonstrating simultaneous reduction in electrical demand and maintenance of dose accuracy and solid-state stability. Conclusions: This study demonstrates that electrical energy consumption can be systematically embedded as a quantitative design variable in pharmaceutical process optimization. The proposed dual-stage DoE strategy establishes a rational framework for developing 3D-printed ASD dosage forms that balance molecular performance and environmental efficiency. 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

Bacterial and fungal infections, together with oxidative stress-mediated damage, remain major challenges in human health and in the protection of materials, highlighting the need for new multifunctional molecules that combine antioxidant and antimicrobial properties. In this context, a new chloropyridine-based derivative, N4,N4-bis((6-chloropyridin-3-yl)methyl)-N1,N1-diethylpentane-1,4-diamine (AMZ), was synthesized via a simple, catalyst-free N-alkylation of N1,N1-diethylpentane-1,4-diamine with 2-chloro-4-(chloromethyl)pyridine in acetonitrile at 55 °C, affording a 62% yield. The structure of AMZ was confirmed by melting point determination, ¹H and ¹³C NMR spectroscopy, and EI–MS analysis. Its antioxidant activity was evaluated using DPPH and FRAP assays with BHT as a reference standard, while antibacterial and antifungal activities were assessed via disk diffusion and microdilution methods to determine inhibition zones and MIC/MBC values. In silico investigations included drug-likeness and ADMET predictions, as well as molecular docking on catalase (PDB: 2CAG) and fungal CYP51 (PDB: 1EA1). AMZ exhibited dose-dependent radical scavenging in the DPPH assay, reaching 76.88 ± 3.20% inhibition at 1000 µg/mL, with an EC₅₀ of 26.03 ± 0.21 µg/mL, close to that of BHT (23.65 ± 0.22 µg/mL). In the FRAP assay, AMZ showed a higher reducing power than BHT at a low concentration (OD₅₀ µg/mL 0.177 ± 0.023 vs. 0.134 ± 0.017), although its FRAP EC₅₀ was higher (700.48 ± 22.54 vs. 400.16 ± 8.67 µg/mL). AMZ displayed broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi, with particularly strong effects on Bacillus subtilis (44.5 ± 0.5 mm; MIC/MBC 0.008 mg/mL) and Aspergillus niger (30 mm; MIC/MBC 0.030 mg/mL), in some cases comparable or superior to streptomycin and fluconazole. In silico analysis indicated that AMZ fulfilled major drug-likeness rules, showed high predicted intestinal absorption (91.14%), and was classified as non-AMES toxic, while docking predicted favorable binding to catalase and CYP51, in agreement with the experimental antioxidant and antifungal activities. These findings highlight the potential of AMZ as a multi-target pyridine-based lead compound that warrants further structural optimization and in vivo evaluation for applications in oxidative-stress-related and infectious conditions. Full article

This study presents the effect of gamma rays of up to 2000 kGy on the chemical structure and the physical properties of a poly(butylene adipate-co-terephthalate) (PBAT) with 48% mol of terephthalic units. PBAT is a polymer with properties similar to polyethylene (PE) but it is biodegradable and not toxic to the environment, and it can be prepared with a renewable content of up to 68.6% weight, with uses in biomedicine and packaging. Previous studies found in the literature have been conducted using low doses and the results were contradictory. The results for gel content and crosslinking efficiency were in agreement with the results found in the literature. Molecular weight decreased and widened with the increase in dose. Proton NMR analysis was used for the first time in PBAT to determine the changes in chemical species, the formation of new chemical species, and the bonds more susceptible to be broken by gamma rays. Both thermal and mechanical properties were explained by the scission of the chains in the amorphous phase and at the boundaries of the crystallites. The thermal parameters most affected by irradiation were the crystallization temperature and temperature of melting after cooling from the melt. Stress and strain at break suffered a continuous decrease with dose until PBAT became fragile at high dose. Full article

New hard tissue formation helps create a more stable seal in endodontic treatment. To achieve this, a novel class of endodontic sealers containing the pro-osteogenic element, strontium (within a BG), embedded in a polydimethylsiloxane matrix (Sr-PDMS) was produced. The properties of this sealer were compared with a commercially available bioactive endodontic sealer, Guttaflow Bioseal (GFBS). Glass was prepared via the melt quench method and incorporated into the GFBS matrix. Its physical properties were tested against the International Organisation for Standardisation (ISO) 6876. For biocompatibility assessment, dose–response proliferation of OCCM-30 cells was quantified by measuring DNA levels in varying concentrations of exogenous calcium and strontium, in culture media conditioned with the novel BG powder, and in sealer discs of the GFBS and novel Sr-PDMS. Two-way ANOVA followed by one-way ANOVA and the Bonferroni post hoc test were applied to the cell viability data. Both the GFBS and novel Sr-PDMS sealants demonstrated physical properties that met ISO 6876, but Sr-PDMS displayed greater radiopacity (p < 0.05), lower solubility, and increased setting time. Both sealants released ions into the immersion solution, with the additional release of Sr from the novel sealer. GFBS displayed evidence of apatite formation. As expected, high concentrations of BG-conditioned media were cytotoxic, but the levels released by the BG in the Sr-PDMS were not cytotoxic with 1:000 dilution and resulted in significantly increased (p < 0.01) cell proliferation compared to the control group. Full article

Fiber actuators underpin soft robots, artificial muscles, and smart textiles. A persistent bottleneck is the fabrication of monodomain liquid crystal elastomer (LCE) microfibers with narrow size distributions while preserving axial alignment. This work establishes a melt-centrifugal spinning (MCS) route with two-step UV fixation that separates flow-induced alignment from network crosslinking. High-speed rotation creates a long extensional jet; an obliquely incident, on-the-fly UV dose at touchdown locks the director, and a post-cure consolidates the network. The obtained LCE microfiber can achieve large reversible contraction (L/L₀ = 0.56), lift a weight, and trigger the tweezers. The method produces a new approach for the fabrication of device-ready LCE actuators, establishes a general design principle for diameter control via curing sequence, and opens a practical path toward artificial muscles and flexible micro robotics. Full article

Polyetheretherketone (PEEK) is a high-performance engineering plastic widely used in aerospace, automotive, and other industries due to its heat resistance and mechanical strength. However, its high friction coefficient and low thermal conductivity limit its use in heavy-load environments. Existing studies have extensively explored the individual effects of thermal processing or irradiation on PEEK. However, the synergistic mechanism between the initial microstructure formed by mold temperature and subsequent irradiation modification remains unclear. This paper investigates the coupled effects of injection molding temperature and electron beam irradiation on the tribology of carbon fiber-reinforced PEEK composites, with the aim of identifying process conditions that improve friction and wear performance under high load by controlling the crystal morphology and cross-linking network. Carbon fiber (CF) particles were mixed with PEEK particles at a 1:2 mass ratio, and specimens were prepared at injection molding temperatures of 150 °C, 175 °C, and 200 °C. Some specimens were irradiated with an electron beam dose of 200 kGy. The friction coefficient, wear rate, surface shape, and crystallinity of the material were obtained using friction and wear tests, white-light topography, SEM, and XRD. The results show that the injection molding temperature of the material influences the friction performance. Optimal performance is obtained at 175 °C with a friction coefficient of 0.12 and wear rate of 9.722 × 10⁻⁶ mm³/(N·m). After irradiation modification, the friction coefficient decreases to 0.10. This improvement is due to the moderate melt fluidity, adequate fiber infiltration, and dense crystallization at this temperature. In addition, cross-linking of chains occurs, and surface transfer films are created at this temperature. However, irradiation leads to a slight increase in wear rate to 1.013 × 10⁻⁵ mm³/(N·m), suggesting that chain segment fracture and embrittlement effects are enhanced at this dose. At 150 °C, there is weak interfacial bonding and microcrack development. At 200 °C, excessive thermal motion reduces crystallinity and adds residual stress, increasing wear sensitivity. Overall, while irradiation reduces the friction coefficient, the wear rate is affected by the initial microstructure at molding. At non-optimal temperatures, embrittlement tends to dominate the wear mode. This study uncovers the synergistic and competitive dynamics between the injection molding process and irradiation modification, offering an operational framework and a mechanistic foundation for applying CF/PEEK under heavy-load conditions. The present approach can be extended in future work to other reinforcement systems or variable-dose irradiation schemes to further optimize overall tribological performance. Full article

Background: Individualized care in veterinary practice optimizes pharmaceutical dose regimens, facilitates disease prevention, and supports animal health by considering the animal’s individual profile. Three-dimensional (3D) printing is a suitable technology for manufacturing both tailored drugs and supplements with enhanced efficacy and reduced adverse reactions. Zinc is used to correct deficiencies, support growth, boost the immune system, and treat specific conditions like zinc-responsive dermatosis in dogs. The purpose of the study was to develop and analyze tailored zinc-loaded filaments for the design of custom-made 3D-printed shapes. Methods: Zinc oxide (ZnO) and artificial beef flavor were incorporated into hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC), respectively, to produce tailored 5% or 10% ZnO-containing filaments for 3D printing. The obtained filaments and 3D-printed forms were characterized using sieve analysis, moisture determination, melting point, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction analysis. Results: The characterization of two placebo and four custom-made 3D-printed ZnO supplements suggested that HPMC is a polymer with poor processability, whereas HPC is suitable for incorporating artificial beef flavor and ZnO. FTIR analysis indicated no interaction between the components. Conclusion: The HPC and 10% flavor mixture can be applied as a matrix for manufacturing 3D-printed forms with ZnO for individualized animal care. Full article

Background: Switching stable liver transplant (LT) recipients from twice-daily immediate-release tacrolimus (IR-Tac) to once-daily MeltDose^® extended-release tacrolimus (LCPT) has been proven safe and well tolerated. Moreover, the switch has been associated with enhanced treatment adherence, improvement of tremors, and preserved renal function. Here, we hypothesized that switching to LCPT early after LT may enhance long-term patient outcomes significantly. Methods: This single-center, observational study investigated the long-term safety of LCPT in a large cohort of LT recipients (n = 100). Allograft function, emerging adverse events, the incidence of rejection reactions, renal function, lipid and glucose metabolism, and treatment adherence were assessed over 24 months. Results: In 56% of patients, the switch was conducted within 4 weeks post-transplantation. Adverse events occurred in 90% of patients during the 24-month follow-up, including gastrointestinal complications (28%), neurological symptoms (28%), skin disorders (26%), metabolic disorders (22%), and fatigue (18%). Seven patients (7%) developed renal insufficiency, and five patients (5%) developed renal failure. Three episodes of chronic graft rejection reactions (3%) and a single transplant failure (1%) were observed over 24 months. LCPT was discontinued in 10 patients. Liver and renal function markers, blood lipids (cholesterol and triglycerides), and glucose levels remained stable over the 24-month follow-up. However, 58% of LT recipients had one of their liver function markers elevated at baseline (i.e., before the switch), 28% had low glomerular filtration rate (GFR < 60 mL/min/1.73 m²), and 18% had high serum creatinine (>1.3 mg/dL). In these subgroups, the early switch to LCPT was associated with a significant decrease in liver enzymes (p < 0.001 for alanine transaminase; p = 0.032 for gamma-glutamyl transferase; and p < 0.001 for total bilirubin) and a significant decrease in serum creatinine levels (p < 0.001). Self-reported treatment adherence was good and consistent throughout the study. Conclusions: The early switch from IR-Tac to LCPT was safe and effective in our cohort and may be particularly beneficial for patients with suboptimal liver and renal function following LT. Full article

Diffuse idiopathic skeletal hyperostosis (DISH), or Forestier’s disease, is a non-inflammatory condition characterized by the calcification and ossification of spinal ligaments and entheses, especially the anterior longitudinal ligament. Its prevalence increases with age and it is more common in males. The term DISH usually refers to the imaging aspects of this condition, while “Forestier’s disease” is used for the clinical correlates of the condition, especially the development of dysphagia. Diagnosis is usually made with conventional radiography, based on the Resnick and Niwayama criteria: flowing osteophytes over at least four contiguous vertebral bodies, the preservation of intervertebral disk space, absent facet and costovertebral joint ankylosis, and absent sacroiliac joint abnormalities. A “melted candle wax” appearance along the spine is typical of the advanced disease. Large anterior osteophytes in the cervical spine lead not only to stiffness and chronic neck pain, but also to compressive symptoms such as dysphagia, dysphonia, and even airway compromise. Digital Dynamic Radiography (DDR), thanks to a flat-panel detector system, captures high-temporal resolution sequential low-dose radiographs at high frame rates in dynamic motion studies to provide functional information. We report the case of a 50-year-old female patient diagnosed with Forestier’s disease. Cervical radiography showed coarse anterior osteophytes and calcifications typical of DISH. The patient complained about persistent cervical pain and significant dysphagia. To investigate the underlying mechanism, a DDR with barium oral administration was performed. The examination confirmed the mechanical narrowing of the pharyngeal lumen caused by bulky anterior osteophytes. Given the severity of the symptoms, the patient underwent a surgical resection of the osteophytic and calcified components, with a subsequent improvement of swallowing function. This case highlights how DDR provides functional and morphological information in patients with dysphagia related to cervical DISH. Full article

In this work, an innovative approach has been established to overcome the intrinsic limitations of poly(L-lactic acid) (PLLA)-based shape memory polymers (SMPs) by introducing γ-ray-induced crosslinking in miscible PLLA/triallyl isocyanurate (TAIC) blends. The crosslinking density can be precisely adjusted by the TAlC content and absorbed irradiation dose, enabling the fabrication of PLLA SMPS with outstanding shape memory properties. In crosslinked PLLA SMPs, the crosslinking point can significantly suppress the cold crystallization and prevent the irreversible chain slippage during deformation in the shape memory process, resulting in not only a high shape recovery ratio (99.5% at 10 wt% TAIC) but also a good cycle stability (maintaining 97.9% after three cycles). Moreover, the crosslinking points as well as the PLLA crystals endow PLLA with triple-shape memory performance, in which both the glass transition temperature and melting temperature serve as switch conditions. Remarkably, even under extreme deformation conditions (strain up to 800%), the crosslinked PLLA SMPs maintain a recovery ratio as high as 99.3%. Our results offer a novel strategy for fabricating high-performance PLLA SMPs with exceptional shape recovery capabilities. Full article

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote bone regeneration. However, conventional surface-attached delivery on absorbable collagen sponges causes a rapid burst release, excessive inflammation, and suboptimal healing. To overcome these limitations, we developed a thermally controlled Poly(DL-lactide-co-glycolide) (P_DLLGA) encapsulation system, designed to stabilize rhBMP-2 and enable controlled release. rhBMP-2 was incorporated in P_DLLGA pellets using the hot-melt extrusion of a lyophilized mixture containing poloxamer 407 and hydroxypropyl-β-cyclodextrin, and terminal sterilization (X-ray irradiation). The released rhBMP-2 maintained its molecular integrity after sterilization and remained stable for up to 732 days in storage, as confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and capillary electrophoresis (CE). Further, high-affinity binding between released rhBMP-2 and BMPR-IA was confirmed by bio-layer interferometry (BLI), and the released protein induced a robust in vitro ALP response, confirming preserved osteogenic activity. Our encapsulation approach for rhBMP-2 using P_DLLGA, including the combination product with β-TCP (LDGraft; Locate Bio, Nottingham, UK), provides a stable and bioactive rhBMP-2 delivery strategy with inherent dose-shielding properties, supporting safe, controlled, and effective bone regeneration therapies. Full article

Additive manufacturing can be regarded as a game-changing approach for paediatric drug development, as children have special drug-related requirements which are rarely met by conventional technologies. Traditional dosage forms have considerable drawbacks, among them dose, excipient safety, and taste issues, which can be resolved by using three-dimensional (3D) printing. Ease of swallowing and an appealing design are among the improvements brought forth by 3D printing techniques. Techniques that have been thoroughly researched in the paediatric field include hot-melt extrusion (HME) coupled with fused deposition modelling (FDM), direct powder extrusion (DPE) and semisolid extrusion (SSE) 3D printing. Selective Laser Sintering (SLS) 3D bioprinting and binder-jet (BJ) 3D printing are other less known but highly useful techniques. A number of studies focus on significant subjects for the paediatric medicine domain, such as the acceptability of the produced formulations, the size of tablets, the design, the concealment of bitter API flavour, and the stability of the dosage forms. The 3D-printed oral formulations are varied: conventional-sized tablets, miniaturised tablets, chewable tablets, and orodispersible films or tablets. Most of the drugs used in the presented studies are essential medicines for children, for which commercial products with flexible doses and age-appropriate characteristics are often lacking. The practical implications of currently published studies and future directions for paediatric pharmaceutical 3D printing are described. Although there is a substantial amount of technical and in vitro data as well as paediatric engagement work on this subject, its translation into clinical practice is still limited. The clinical efficacy of 3D-printed dosage forms has to be further researched, since only a few studies have targeted this aspect. Full article