262,184 research outputs found

    A floating 3D printed formulation for the coadministration and sustained release of antihypertensive drugs - Underlying CT data

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    Underlying CT data of Zgouro et al (2024) &quot;A floating 3D printed polypill formulation for the coadministration and sustained release of antihypertensive drugs&quot;, International Journal of Pharmaceutics, 655, 124058, https://doi.org/10.1016/j.ijpharm.2024.124058 Microfocus Computed Tomography (&mu;CT) X-ray microfocus computed tomography (&mu;CT) was employed for the characterization of the microstructure of the printed object, assessing the overall volume, porosity, local thickness and other printing defects. The imaging took place at the University of Southampton&rsquo;s &mu;-VIS X-ray Imaging Centre (www.muvis.org) / 3D X-ray Histology facility using a customized &mu;CT scanner optimized for 3D X-ray histology (www.xrayhistology.org) (Katsamenis et al., 2023) based on Nikon&rsquo;s XTH225ST system (Nikon Metrology, Castle Donington, UK). The scanner was operated at 110 kVp / 90 &mu;A (9.9 W), with the X-ray beam prefiltered using 0.04 mm of aluminum. The source-to-object and source-to-detector distances were 28.4 mm and 1136.7 mm, respectively, resulting in a magnification factor of 40x. Acquisition parameters included 2201 projections, averaging 4 frames per projection, with an exposure time of 177 ms per projection. The 2850 x 2850 dexels detector was binned 2x (virtual detector: 1425 &times; 1425 dexels), resulting in an isotropic voxel edge of 7.5 &mu;m. The reconstructed data underwent visualization and analysis using Dragonfly software (Comet Technologies Canada Inc.; software available at http://www.theobjects.com/dragonfly).</span

    Bone matrix material properties on the micro- and nanoscale

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    The evaluation of fracture risk in osteoporotic patients, which is still mostly based on bone mineral density (BMD) measurements, constitutes a major clinical challenge. Despite the fact that BMD is highly correlated with fracture risk in large populations, it unfortunately fails to be an accurate predictor for the individual. To increase the accuracy of fracture risk evaluation, a better understanding of all factors affecting bone fracture behaviour, including (but not limited to) BMD, is needed. This means a deeper understanding of bone’s material properties and structure-function relationship is required.Mammalian bones are composed of mineralized type I collagen fibrils immersed in a matrix of non-collagenous proteins (NCPs). This fundamental unit assembles into progressively larger features in a hierarchical manner, supplying bone with various “lines of defence” against catastrophic failure. Optimal load transfer and energy dissipation mechanisms have, to some extent, been discovered within bone’s nanostructure on which NCPs have been proposed to play a crucial role. Yet, it is largely unknown if integration of such mechanisms occurs to any other hierarchical level. This thesis attempts to answer this question for the osteonal level of cortical bone. The feature dominating this level is a hollow tubular structure of a few hundred micrometres in diameter, the osteons, consisting of concentric aligned lamellae. Lamellae range from 3 -10 ?m in thickness and between them lie interlamellar areas (often referred to as thin lamellae).This thesis is the outcome of three studies. The first focuses on the aforementioned osteonal features, namely lamellae and interlamellar areas, studying their structure, composition and their mechanical behaviour during loading. For this purpose a series of experimental techniques were used including ?-RAMAN microscopy, atomic force microscopy (AFM), AFM cantilever-based nanoindentation and in-situ AFM analysis during microtensile testing. It was shown that interlamellar areas differ from lamellae by (a) being collagen-deficient and NCP-rich, (b) having a different arrangement of collagen fibres, (c) being more compliant when no load is applied to the bone and (d) exhibiting higher strains under loading conditions. Finally, stable crack propagation was for the first time captured in a time-lapsed fashion within the interlamellar areas by means of AFM, further proving their significant contribution towards fracture toughness.The second is a technical study for the development of a method capable for generating full fracture-resistance curves (R-curves) of small bone samples where crack propagation cannot easily be observed. The outcome was the development of a novel computer-aided videography method, “whitening-front tracking” method, which uses the whitening effect formed by the development of the damage in front of the crack-tip (frontal process zone) to indirectly track the crack propagation which is needed for the generation of the R-curve.The new method was then applied in the third study to correlate the ultimate toughness of human cortical bone, i.e. “fracture toughness” and “crack growth resistance” at the tissue-level, with the elasticity inhomogeneity between lamella and interlamellar areas at the osteonal-level and the damage-formation resistance at the micro-level. In this study the mechanical properties of bone in tissue-, micro- and osteonal-level were measured by means of the “whitening front tracking”, reference point indentation (RPI) and AFM cantilever-based nanoindentation methods respectively. The results revealed a correlation of toughness and crack-growth resistance at the tissue-level with the elastic inhomogeneity between the sub-osteonal features. That is, the higher the difference between the moduli of lamellae and interlamellar areas the higher the toughness of the tissue. Furthermore, toughness and crack-growth resistance correlated with bone’s “resistance to damage” as it was characterised by RPI at the micro-level. Finally, these measured suggested age-related degradation of the mechanical properties at all three levels measured. Overall, the results presented in this thesis propose that osteons are the principal component of a previously unknown proactive mechanism which transfers load and movement in a manner analogous to engineered “elastomeric bearing pads”. This ability originates from the elastic inhomogeneity between the lamellae and the interlamellar areas which allows osteons to adapt to high stresses without damage formation

    X-ray microfocus Computed Tomography: a powerful tool for structural and functional characterisation of 3D printed dosage forms

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    One of the most promising advances in modern pharmaceutical technology is the introduction of three-dimensional (3D) printing technology for the fabrication of drug products. 3D printed dosage forms have the potential to revolutionize pharmacotherapy as streamlined production of structurally complex formulations with optimal drug releasing properties is now made possible. 3D printed formulations are derived as part of a process where a "print-head" deposits, or sinters material under computer control to produce a drug carrier. However, this manufacturing route inherently generates objects that deviate from the ideal designed template for reasons specific to the 3D printing method used. This short opinion article discusses the potential of high-resolution non-destructive 3D (volume) imaging by means of X-ray microfocus Computed Tomography (μCT) as a Process Analytical Technology for the structural and functional characterisation of 3D printed dosage forms. </p

    3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery

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    3D printing has been recently employed in the design and fabrication of medicine, aiming to improve their properties and release behavior. In the current work an oral solid dosage form was designed by Fused Deposition Modeling (FDM), using a custom built filament comprised of a water soluble polymer polyvinyl alcohol (PVA), mannitol and hydrochlorothiazide (HCTZ) as model drug and further co-formulated via Hot-Melt Extrusion (HME). This composition was printed as the inner part of a three-compartment hollow cylinder dosage form using a dual extrusion 3D FDM printer, whereas the outer parts of the formulation consisted of water-insoluble polylactic acid (PLA). The produced formulations were characterized by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Release studies were performed in pH 1.2 and 6.8 whereas four-dimensional X-ray micro focus Computed Tomography (4D-CT), was employed to visualize volumetric and morphological changes of the formulations during the dissolution procedure. The results showed that HCTZ was incorporated in the amorphous state. Dissolution studies demonstrated that HCTZ exhibited zero-order kinetics whereas 4D-CT revealed a bi-directional smooth and homogenous reduction of PVA further corroborating the dissolution studies. The results showed that FDM printing might be used to ‘fine tune’ the release of drug molecules

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Protecting Animals 36: Author Witi Ihimaera

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    In this very special episode of Knowing Animals I am joined by beloved New Zealand author Witi Ihimaera. Witi has written many books featuring nonhuman animals. He offers us a non-colonial lens through which to think about the human/nonhuman relationship

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries

    <i>In silico</i> simulations of diffusion tensors and tortuosity in cells grown on 3D-printed scaffolds for tissue engineering

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    Tissue engineering is set to revolutionise regenerative medicine, drug discovery, and cancer biology. For this to succeed, improved 3D imaging methods that penetrate non-invasively into the developing tissue is fundamental to guide the design of new and improved 3D supports. In particular, it is very important to characterise the time- and space-heterogeneous pore network that continuously changes as the tissue grows, since delivery of nutrients and removal of waste is key to avoid the development of necrotic tissues. In this paper, we combine high-resolution microfocus Computed Tomography (μCT) imaging and in silico simulations to calculate the diffusion tensor of molecules diffusing in the actual pore structure of a tissue grown on 3D-printed plastic scaffolds. We use such tensors to derive information about the changing pore network and derive tortuosity, a key parameter to understand how pore interconnection changes with cell proliferation. Such information can be used to improve the design of 3D-printed supports as well as to validate and improve cell culture protocols

    Controlled release of 5-Fluorouracil from alginate beads encapsulated in 3D printed pH-responsive solid dosage forms

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    Three-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/
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