1,721,001 research outputs found
Desarrollo de un nuevo medicamento de liberación prolongada de Tolcapone
Full text linkEl objetivo del presente estudio ha sido la investigación y desarrollo de un nuevo medicamento sólido de Tolcapone, en forma farmacéutica de comprimido de liberación prolongada y administración oral con una pauta posológica preferente de 1 administración cada 12 o 24 horas, diseñado específicamente para una nueva indicación terapéutica: el tratamiento de la polineuropatía amiloidea familiar.
Este objetivo ha implicado la investigación de las características químicas, físicas y tecnológicas del principio activo vehiculizado, el diseño de una formulación robusta y adecuada, establecer la tecnología de fabricación óptima y el estudio del comportamiento cinético de liberación y disolución del fármaco partir de la forma farmacéutica, realizando ensayos “in vitro” e “in vivo” en modelo animal.
La selección de los comprimidos matriciales como forma farmacéutica de liberación prolongada de elección ha sido motivada por las características físicoquímicas y tecnológicas del principio activo y por tratarse de formas farmacéuticas fácilmente industrializables.
Se han llevado a cabo 3 líneas de investigación en paralelo en función del tipo de matriz utilizada y el comportamiento de la misma: matrices hidrófilas de hinchamiento ilimitado, matrices hidrófilas de hinchamiento limitado y matrices hidrófobas.
Los comprimidos matriciales hidrófilos de hinchamiento ilimitado son los que han permitido obtener mejores resultados.
La compresión directa se considera la tecnología de fabricación de elección por las ventajas que presenta. Tolcapone es apto para su compresión vía directa si se formula junto a los excipientes adecuados para compensar sus deficiencias.
El excipiente seleccionado para la formación de la matriz polimérica ha sido la hidroxipropilmetilcelulosa, excipiente muy utilizado para la formulación de este tipo de comprimidos. Se ha decidido formular con celulosa microcristalina como diluyente ya que por sus características intrínsecas es capaz de compensar la cohesividad deficitaria que presenta el principio activo. Se añaden a la formulación un deslizante, sílice coloidal anhidra, y dos lubrificantes, estearato magnésico y talco.
Se han realizado diferentes formulaciones con concentraciones de hidroxipropilmetilcelulosa comprendidas entre un 20 % y un 35%. Se ha confirmado el hecho de la dependencia existente entre la cantidad de agente retardante en la
formulación y la velocidad de liberación del fármaco a partir del comprimido matricial. A mayor cantidad de hidroxipropilmetilcelulosa en la formulación, más lenta es la liberación del fármaco, existiendo una relación que se ajusta a un modelo exponencial.
Una disminución en el tamaño de partícula del principio activo ha dado lugar a una cinética de disolución del fármaco más lenta cuando el excipiente retardante se encuentra por debajo del 29% en la formulación.
Para demostrarlo, se ha realizado un estudio estadístico cuyos resultados permiten afirmar que existen diferencias estadísticamente significativas entre las cinéticas de disolución realizadas con los comprimidos matriciales fabricados con principios activos de diferente tamaño de partícula , siendo más rápida la correspondiente a la formulación fabricada con tolcapone de tamaño de partícula mayor.
A pesar de que el modelo animal escogido para el estudio (perro) resultó no ser el adecuado para ensayar este tipo de formulaciones de liberación prolongada debido a las diferencias considerables a nivel de tracto gastrointestinal (diferente tránsito, diferente pH gástrico, etc) existente entre perro y humano, se propone la formulación con una concentración de hidroxipropilmetilcelulosa del 29% como fórmula definitiva y apta para una administración cada 12 horas.The aim of this study was the research and development of a new solid formulation of Tolcapone, in a sustained release tablet dosage form for an oral administration with a preferred dosage regimen of 1 administration every 12 or 24 hours, designed specifically for a new indication therapy: treatment of Familial Amyloid Polyneuropathy.
This goal has involved the investigation of the chemical, physical and technological characteristics of the active ingredient, the design of a robust and suitable formulation, establish an optimal manufacturing technology and study the kinetic behavior of liberation and dissolution of the pharmaceutical form, conducting trials "in vitro" and "in vivo" in animal model.
The selection of matrix tablets and sustained-release dosage form of choice has been motivated by the physico-chemical and technological characteristics of the active substance and for being easily industrialized dosage forms.
Three different lines have been developed in parallel depending on the type of matrix used and its behaviour: unlimited swelling hydrophilic matrices, limited swelling hydrophilic matrices and hydrophobic matrices.
The best results have been obtained with unlimited swelling hydrophilic matrices.
Direct compression is considered a manufacturing technology of choice for the advantages presented. Tolcapone is suitable for compression straightaway if it is formulated with suitable excipients to improve its limitations.
The carrier selected for forming the polymer matrix has been hydroxypropylmethylcellulose, excipient widely used for the formulation of this type of tablets. It has been decided formulated with microcrystalline cellulose as a diluent because its intrinsic characteristics are able to compensate the deficit of cohesiveness of the active ingredient. A glidant, colloidal anhydrous silica, and two lubricants, magnesium stearate and talc, are added to the formulation.
They were performed with different concentrations of hydroxypropylmethylcellulose formulations between 20% and 35%. It has confirmed the fact the dependence between the amount of retarding agent in the formulation and the release rate of the drug from the matrix tablet. A greater amount of hydroxypropylmethylcellulose in the formulation, the slower the drug release, having a relationship that conforms to an exponential model.
A decrease in particle size of the active ingredient has resulted in dissolution kinetics slower drug when the retardant excipient is below 29% in the formulation.
To prove it, it has done a statistical study whose findings are such that there are statistically significant differences between the kinetics of dissolution made to matrix tablets made with active ingredients of different particle size, being faster corresponding to the formulation made with tolcapone larger particle size.
Although the animal model chosen for study (dog) resulted to be not suitable for testing such sustained release formulations due to the significant differences at the level of the gastrointestinal tract (different transit different gastric pH, etc) between dog and human, the formulation is proposed with a concentration of 29% hydroxypropylmethylcellulose as final and suitable formula for administration every 12 hours
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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
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