Search Results (333)

Hot-melt extrusion (HME) is widely used in pharmaceutical manufacturing; however, reliable analytical tools are required to simultaneously monitor drug content and excipient stability under thermal processing. In this study, a selective and robust HPLC–UV method was developed and validated for the concurrent determination of triamcinolone acetonide (TA) and triethyl citrate (TEC) in HME polymeric films and porcine buccal mucosa. Chromatographic separation was achieved on a C₁₈ column using an acetonitrile–water mobile phase (30:70, v/v) at a flow rate of 0.6 mL min⁻¹, with detection at 240 nm for TA and 210 nm for TEC. The method was validated for selectivity, linearity, precision, and accuracy, including selectivity assessment in the presence of mucosal extract and polymeric matrix components, and recovery of TA in porcine buccal mucosa. Excellent linearity was obtained over 0.20–12.5 µg mL⁻¹ for TA and 4.5–30.0 µg mL⁻¹ for TEC (r ≥ 0.998), with precision below 6.3% and TA recovery exceeding 94%. Application to extruded films confirmed uniform analyte distribution and enabled simultaneous monitoring of TA degradation and TEC loss under thermal stress. These results demonstrate that the proposed method is suitable for formulation development, process monitoring, and stability assessment of HME-based pharmaceutical systems. Full article

Background: Hot-melt extrusion (HME) is a promising technology for the manufacturing of drug products; however, its application is limited by elevated thermal and shear stresses that may induce degradation of thermolabile active pharmaceutical ingredients. One of the approaches to reducing processing temperatures is the use of polymeric systems with tailored thermal and rheological properties. The aim of the study was to develop an approach for the design of polymeric systems exhibiting a transient plasticization window, enabling a reduction in melt viscosity and improved processability under low-temperature extrusion conditions, followed by the formation of a structurally coherent matrix upon cooling. Methods: The compatibility of the initial polymers was assessed using laser microinterferometry. Based on the obtained data, three- and four-component polymeric compositions were designed and prepared by hot-melt extrusion. The resulting materials were characterized by differential scanning calorimetry, melt rheology analysis, and storage stability assessment. Thermal and rheological data were used to iteratively optimize the polymeric systems. Results: A four-component polymeric system based on PVP K-29/32, PEG 400, PEG 1500, and HPC EF was developed, suitable for processing by hot-melt extrusion at 70 °C. The final system enabled formation of a homogeneous extrudate, exhibited reproducible rheological behavior, and remained stable in the solid-state during storage, with no evidence of cold flow. Conclusions: It was established that, in the design of polymeric systems for hot-melt extrusion, the key factor is not achieving the lowest possible glass transition temperature, but rather the design of a system in which viscosity is transiently reduced under processing conditions and followed by structural stabilization upon cooling. The proposed approach may be applied in the development of polymeric premixes for the preparation of dosage forms by hot-melt extrusion, including those incorporating thermolabile active pharmaceutical ingredients. Full article

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

Background: Fused deposition modeling (FDM) is one of the most well-known and often published methods for 3D-printed drug delivery systems. In early scientific reports, the active pharmaceutical ingredients were added by soaking, but later, a new milestone was established, after researchers started to manufacture their own filaments by hot-melt extrusion (HME). The number of publications covering this method has multiplied in the last decade, a wide range of natural and synthetic polymers have been tested with versatile active pharmaceutical ingredient components, and various printing parameters and their effects have been investigated. Objectives: In this review, we aim to synthesize how the available quality by design approaches and the scientific results established so far can facilitate the creation of a guideline for appropriate quality production of HME-FDM 3D-printed pharmaceuticals. Methods: Based on PRISMA 2020 guidelines, a systematic search of relevant publications from 2015 to 2025 was carried out using the PubMed database. Twenty-six articles were included, based on number of monitored parameters and methodological description. Reporting of important quality processes and material parameters was assessed. Results: HME, the FDM, and analytical testing experiences were compared and collected into three tables from the selected publications. In two different sections, the pharmacopeial dosage-form tests and the involvement of process analytical technologies (PAT) were also analyzed. We found that reporting of influential parameters is heterogenous, and lack of robust reporting schemes limits the development of QbD approaches. Conclusions: Regarding the data, trends were synthetized, and a guideline was created which is limited by inconsistent parameter reporting. Full article

The aim of the study was to modify polylactide with zinc oxide nanoparticles (ZnO), raspberry leaf extract (E), and a combined ZnO/extract system (EZnO) in order to prepare novel packaging materials via a solvent-free method, namely cast extrusion. Physicochemical properties: Morphology (GPC, SEM, FTIR), mechanical (tensile tests, puncture), barrier (WVTR, OTR, UV-Vis) and water contact angle for PLA-based films with two thickness ranges were investigated. Additionally, antimicrobial (antibacterial, antifungal and antiviral) tests were performed. GPC results revealed that the presence of the extract counteracted biopolyester degradation during hot melt processing. The best mechanical properties (TS ca. 50 MPa, EB ca. 18%) were obtained for PLA modified with raspberry leaf extract (PLA/E). EZnO addition led to the highest increase in oxygen (with 25%) and water vapor (up to ca. 28%) barrier properties. The material with EZnO addition was also found to be the only one to demonstrate antibacterial effectiveness, although the activity was insignificant. However, the incorporation of EZnO into the biopolymer matrix enhanced its antiviral properties, resulting in the complete inactivation of Φ6 bacteriophage particles used as a surrogate of SARS-CoV-2 virus. Full article

Polyphenols have attracted considerable scientific interest over recent years due to their broad spectrum of biological activities, including antioxidant, cardioprotective, anti-inflammatory, antidiabetic, and anticancer properties. However, their practical application is often limited by unfavorable physicochemical characteristics, particularly low aqueous solubility. Consequently, amorphous solid dispersions (ASDs) have been extensively investigated as a formulation strategy to overcome these limitations. This article represents the first part of a two-part review and presents the current state of the art in amorphous solid dispersions of polyphenols. The available literature is systematically summarized with respect to the investigated polyphenolic compounds, the employed carriers (with particular emphasis on polymeric systems), the preparation methods, and the solid-state characterization techniques used to confirm amorphization. Both single-component systems and binary combinations of polyphenols reported in the literature are considered. The collected data are presented in tabular form and complemented by a heat map illustrating the frequency of reported polyphenol–carrier combinations. The aim of this review is to organize the available knowledge, identify the most extensively studied systems, and highlight research areas that remain underexplored. A detailed discussion of the pharmaceutical benefits and mechanistic aspects of polyphenols in ASD systems will be provided in Part II. Full article

Background/Objectives: This study aimed to develop bilayer tablets using hot-melt pneumatic extrusion (HMPE)-based 3D printing for the integrated treatment of allergic rhinitis and asthma. The formulation combined levocetirizine dihydrochloride (immediate release) and montelukast sodium (delayed release) within a single dosage form to provide a sequential-release formulation strategy relevant to the intended pharmacological roles of the two drugs. Distinct polymer matrices were selected for each drug layer to ensure mechanical robustness, stability, and appropriate release characteristics. Methods: The printed tablets were systematically characterized by mechanical testing, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and in vitro dissolution. Drug content uniformity was evaluated in accordance with USP <905>. Results: The tablets satisfied USP standards for content uniformity and exhibited sufficient mechanical strength for handling and packaging. DSC and PXRD analyses indicated amorphization of levocetirizine within the polymer matrix, while the amorphous state of the raw montelukast used in this study was retained after printing. In vitro dissolution tests demonstrated immediate release of levocetirizine in acidic medium (pH 1.2) and delayed release of montelukast at intestinal pH (6.8), thereby achieving the intended dual-phase release profile. Conclusions: These findings demonstrate the feasibility of fabricating an HMPE-based 3D-printed bilayer tablet integrating immediate-release levocetirizine and delayed-release montelukast, with reproducible dual-phase release and drug-specific solid-state and performance characteristics within a single oral dosage form. 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

Sustainable nanotechnologies derived from renewable resources are increasingly being positioned at the interface of green chemistry, advanced drug delivery, and translational pharmaceutics. Over the past decade, lignocellulosic nanomaterials, chitin/chitosan platforms, polysaccharide-based nanogels and nano-enabled hydrogels, lignin- and polyphenol-derived nanostructures, and bio-based lipid nanocarriers have been engineered through progressively eco-efficient routes, including solvent-minimized self-assembly, nanoprecipitation, spray drying, hot-melt extrusion, and microfluidic-assisted fabrication. This work provides a structured evidence map of nano-enabled drug delivery and therapeutic platforms derived from renewable biological resources. Specifically, we aim to (i) identify and classify nanoplatform classes and renewable feedstocks; (ii) summarize reported pharmaceutical critical quality attributes (CQAs) and performance and safety endpoints; and (iii) appraise how “renewability” and “green” claims are evidenced (feedstock origin vs. process sustainability) and how frequently translational readiness factors (scalability, quality control, regulatory alignment) are addressed. We critically compare renewable and conventional nanomaterial platforms across key translational dimensions, including carbon footprint, batch consistency, biodegradability, functional tunability, safety/persistence, and scale-up maturity. Finally, we delineate a practical translational pathway—from biomass sourcing and fractionation to nanoformulation, characterization/stability, and GMP scale-up—highlighting cross-cutting enablers such as lifecycle assessment, EHS/toxicology risk assessment, quality-by-design, and regulatory alignment. Collectively, the evidence supports renewable nanomaterials as viable, scalable candidates for next-generation therapeutics, provided that variability control, standardized characterization, and safety-by-design principles are embedded early in development. 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

The purpose of this study is to combine 3D printing and hot-pressing to improve polyvinylidene fluoride (PVDF) by making its surface smoother, enhancing crystallinity and electrical and mechanical performance. Before printing, PVDF filament was analyzed using rheology, differential scanning calorimetry (DSC), Thermogravimetric Analysis (TGA), and extrusion tests. Based on these results for printing, 250 °C was fixed as the optimized printing temperature. PVDF samples were printed using an Ultimaker S5 dual-nozzle 3D printer, with a size of 30 × 30 × 0.2 mm³. After printing, samples were hot-pressed at five different temperatures, 100, 125, 150, 175, and 200 °C, for 10 min each. Then, the hot-pressed samples were tested using morphology, Fourier transform infrared (FTIR), X-ray diffraction (XRD), DSC, tensile, and electrical properties. From the morphology, the sample thickness decreased from 0.25 to 0.24 mm, making the surface smoother, removing pores after hot-pressing. From FTIR and XRD results, all samples showed similar patterns, but the hot-pressed sample showed slightly stronger β-phase diffraction and peaks near 20° and 840, 1066, and 1275 cm⁻¹, indicating better crystal ordering. The DSC results showed a small increase in melting temperature and stable thermal behavior after hot-pressing, confirming improved thermal stability. The tensile property results confirmed that the hot-pressed samples, around 150 and 175, showed higher strength and better flexibility. The electrical I-V test showed stable and uniform conductivity, and the hot-pressed samples performed more consistently. Overall, hot-pressing improved the surface quality, crystallinity, mechanical, and electrical properties of 3D-printed PVDF, making it more reliable for advanced applications. Full article

Isoflavones are plant-derived polyphenols with broad biological activity; however, their application in topical formulations is limited by poor aqueous solubility. The aim of this study was to enhance the aqueous solubility of formononetin using a solvent-free hot-melt extrusion (HME) approach and to enable its incorporation into a hydrogel formulation suitable for skin delivery. Amorphous formononetin-based systems were prepared by HME using polymeric carriers and hydroxypropyl-β-cyclodextrin, with and without prior inclusion complex formation. The resulting formulations were characterized using XRPD, DSC, and FT-IR/ATR to assess amorphization and intermolecular interactions. Aqueous solubility and skin permeability were evaluated using solubility testing, PAMPA, and Franz diffusion cells. The optimized amorphous system exhibited a substantial increase in apparent aqueous solubility compared to crystalline formononetin while maintaining comparable permeability. Cyclodextrin–formononetin interactions were effectively generated during the extrusion process, rendering pre-inclusion unnecessary. The selected system was successfully incorporated into a hydrogel matrix. This study demonstrates that solvent-free HME combined with cyclodextrins is an effective strategy for improving formononetin solubility and enabling its application in hydrogel-based topical delivery systems. 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

To achieve an optimal balance of mechanical properties in low-cost alloy systems, this study tailored a heterogeneous bimodal structure in dilute Mg-0.4Al-0.3Ca-0.2Mn-xSn alloys (x = 0, 0.1 wt.%) and systematically investigated the critical role of trace Sn microalloying during hot extrusion. Mg-0.4Al-0.3Ca-0.2Mn-xSn alloys were fabricated via melting, homogenization, and subsequent hot extrusion at 320 °C. Trace Sn addition induced the formation of uniformly distributed CaMgSn phases within the homogenized matrix, facilitating a synergistic enhancement of strength and ductility. Specifically, the extruded alloys exhibited a characteristic bimodal grain structure consisting of coarse un-dynamic recrystallized (unDRXed) grains and fine dynamic recrystallized (DRXed) grains. Sn microalloying effectively refined the DRXed grains from 2.66 μm to 2.11 μm and significantly boosted the elongation (EL) from 12.9% to 26.3% while maintaining an Ultimate Tensile Strength (UTS) of 274 MPa. The Sn-containing secondary phases served as potent sites for particle-stimulated nucleation (PSN), thereby promoting the DRX process and reducing the texture intensity from 20.89 to 9.99. Overall, the superior strength-ductility synergy is primarily governed by the formation of the heterogeneous bimodal structure, where trace Sn facilitates grain refinement and texture weakening through PSN mechanisms, providing a robust strategy for the design of high-performance dilute magnesium alloys. Full article

Fenbendazole is an important anti-parasitic medicine widely used in the veterinary field and has recently been considered as a possible anti-cancer agent in humans by some researchers. Fenbendazole encounters challenges in its usage due to its limited aqueous solubility, which consequently impacts its therapeutic efficacy. In this work, an in vitro mechanistic investigation was conducted to evaluate the compatibility, amorphization behaviour and dissolution profile of fenbendazole dispersed in Soluplus^® using the solid dispersion approach via hot-melt extrusion. Three different fenbendazole/Soluplus^® ratios were formulated and characterised through systematic experimentation. Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray (EDX) and Fourier Transform Infrared Spectroscopy (FTIR) were employed for thermal, physical, chemical and morphological analyses. The solubility of the drug formulation during a dissolution test was investigated using Ultraviolet–Visible (UV–Vis) spectrophotometric measurements. In vitro dissolution testing in acidic and neutral media was employed as a controlled environment to compare dissolution behaviour among different loadings. The extrudates demonstrated markedly enhanced apparent solubility compared to neat fenbendazole, with the 5% formulation showing the highest dissolution rate (approximately 85% after 48 h). This improvement can be attributed to better wetting properties and drug dispersion within the Soluplus^® matrix. This innovative strategy holds promise in surmounting fenbendazole’s solubility limitations, presenting a comprehensive solution to enhance its therapeutic effectiveness. Full article