1,720,996 research outputs found
3D printed hollow microneedles for transdermal insulin delivery
No full textMicroneedles (MN) are miniature devices of a maximum length of 1000 μm, capable of perforating painlessly stratum corneum and releasing their active content in the skin layers beneath. The significance of MNs lies on the fact that they have the potential to substitute the fear inducing injections, while avoiding first pass effect or other possibly unwished metabolic changes of the oral administration1. In the current study 3D printed microneedles were fabricated by means of liquid crystal display (LCD) vat polymerization 3D printing technology for the transdermal delivery of human insulin in vitro.In the current study the structural features of two different 3D printed 6x6 HMN geometries were assessed. Non-destructive 3D (volumetric) imaging by means of μCT demonstrated that the 3D printing method used in this study allows for high consistency and reproducibility with respect to needles’ geometric characteristics. Diffusion studies demonstrated that syringe-like HMNs were more effective upon insulin administration compared with curved pyramid ones. Although syringe-like geometry penetrates skin at higher insertion force, it is probably more suitable for macromolecular drug delivery which might be attributed to the geometrical characteristics of the microneedles
Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients
No full textIn pharmaceutical formulations, pharmacokinetic behavior of the Active Pharmaceutical Ingredients (API's) is significantly affected by their dissolution profiles. In this project, we attempted to create personalized dosage forms with osmotic properties that exhibit different API release patterns via Fused Deposition Modelling (FDM) 3D printing. Specifically, cellulose acetate was employed to create an external shell of an osmotically active core containing Diltiazem (DIL) as model drug. By removing parts of the shell (upper surface, linear lateral segments) were created dosage forms that modify their shape at specific time frames under the effect of the gradually induced osmotic pressure. Hot-Melt Extrusion (HME) was employed to fabricate two different 3DP feeding filaments, for the creation of either the shell or the osmotic core (dual-extrusion printing). Printed formulations and filaments were characterized by means of (TGA, XRD, DSC) and inspected using microscopy (optical and electron). The mechanical properties of the filaments were assessed by means of micro- and macro mechanical testing, whereas micro-Computed Tomography (μCT) was employed to investigate the volumetric changes occurring during the hydration process. XRD indicated the amorphization of DIL inside HME filaments and printed dosage forms, whereas the incorporated NaCl (osmogen) retained its crystallinity. Mechanical properties’ testing confirmed the printability of produced filaments. Dissolution tests revealed that all formulations exhibited sustained release differing at the initiation time of the API dissolution (0, 120 and 360 min for the three different formulations). Finally, μCT uncovered the key structural changes associated with distinct phases of the release profile. The above results demonstrate the successful utilization of an FDM 3D printer in order to create osmotic 3D printed formulations exhibiting sustained and/or delayed release, that can be easily personalized containing API doses corresponding to each patient's specific needs.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Metal Additive Manufacturing
No full textThe following reprint explores the transformative advancements in metal additive manufacturing (AM) across cutting-edge industrial applications. Addressing key challenges in design, performance optimization, and application-specific development, it serves as a platform for state-of-the-art research and innovative methodologies. The collection features 10 high-quality papers authored by 47 contributors from 22 esteemed institutions, highlighting substantial interdisciplinary collaboration efforts. Built upon 381 published works, these studies present novel insights into material properties and real-world applications. With over 9,600 views in the first nine months, this reprint underscores the growing significance of metal AM and its accelerating industrial adoption
Controlled release of 5-Fluorouracil from alginate beads encapsulated in 3D printed pH-responsive solid dosage forms
No full textThree-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments’ mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.<br/
A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery
No full textFused Deposition Modelling (a.k.a. FDM-3D printing) has been previously employed in the development of personalized medicines with unique properties and release behavior. In the present work, a bilayer dosage form containing two anti-diabetic drugs with different daily dosage regimens; i.e. metformin and glimepiride, was manufactured via FDM 3D printing, studied using a variety of techniques and characterized in vitro. Metformin and glimepiride were embedded in Eudragit® RL sustained release layer and polyvinyl alcohol (PVA) layer respectively. Incorporation of more than one API's into the formulation is desirable, as it increases patient compliance and reduces cost of treatment, especially when distinct dosages of API's can be adjusted individually in situ, in order to meet each patient's specific needs, a capability provided by 3D printing. A number of different preparation methods, which involved different plasticizers and extruders, were tested on manufacturing Eudragit® RL drug-loaded filaments for printing the sustained release layer. The properties of the produced filaments were assessed by means of mechanical and physicochemical characterization techniques and the filaments with the optimum properties were used for printing. Microfocus computed tomography (μCT) imaging-based actual/nominal comparison analysis showed a printing accuracy ranging between −100, +200 μm, while X-ray (XRD) diffractograms revealed the incorporation of the (initially crystalline) API's as amorphous dispersions into polymer matrices. Dissolution tests showed sufficient drug release for both drugs in desired time frames (75 min for glimepiride and 480 min for metformin). The results from the current study emphasize the potentiality of 3D printing technology for tailor-made solid dosage forms for combined pharmacotherapy, even at the cases when API's with different desirable release profiles are employed.</p
Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives
No full textIn the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.</p
Tailored sticky solutions: 3D-printed miconazole buccal films for pediatric oral candidiasis
No full textIn this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity
Mechanochemical-induced swelling–activation of a gastric-deployable 4D-printed polypill inspired by natural hygromorphic actuators
No full textGastroretentive drug delivery systems can improve adherence in patients with chronic diseases (CDs), but current options lack dose flexibility and involve complex fabrication methods. Inspired by the hygroscopic deformation observed in multilayered pine cone scales, wherein hydration of the outer active layer induces cone closure, a one-step fabrication method of a personalized 4D-printed water-actuated four-arm polypill is demonstrated in this study. The bilayer-arm polypill self-deploys upon ingestion to prolong gastric retention and sustain drug release. By inversing the orientation of the swellable active layer at the polypill arms compared to pine cone scales, a differential swelling strain develops generating bending force that enables polypill deployment to constrain passage through the pylorus. Finite-element analysis is used to model spatial changes in polymer phase swelling to ensure adequate deployment within the timeframe of gastric emptying. In a stomach model, the polypill expanded to 30 mm over 2 h, exceeding the diameter of the stomach model's distal end. In an in vitro release screening, biocompatible polymer composites capable of providing up to 6 days of release for a three-drug combination for tuberculosis–HIV coinfected patients are identified. The bioinspired 4D-printed polypill can serve as drug delivery platform for a range of CDs.</p
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