1,720,958 research outputs found
PEG microparticles loaded with diazepam obtained by particles from gas saturated solution technique: production, characterisation and in vitro dissolution
No full textUnderstanding solid-state properties of triglycerides used in pharmaceutical and food microencapsulation
No full textHydrophobic materials, in particular hydrogenated vegetable oils, HVO, are extensively used as coating materials in food and pharmaceutical systems. Correct application of these coatings requires an evaluation of their behaviour as a function of various parameters such as melting temperature, solubility, concentration and/or pH. The purpose of this study was to assess the physico-chemical properties of an HVO in terms of composition, crystallisation, phase transition and polymorphism using a variety of analytical techniques, such as electrospray mass spectrometry (ESI-MS), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). High-resolution ESI-MS allowed establishment of the HVO main composition of long-chain triglycerides (average molecular weight 1183 Da). DSC results showed that thermal history determines the formation of at least two polymorphs of HVO, namely two different crystal forms, assigned as form α, melting point (m.p.) 48 °C, and form β', m.p. 60 °C. A third polymorph, the more thermodynamically stable β-form, having a melting point at 62 °C, is obtained by solution-mediated re-crystallisation. Phase transformation paths were investigated by isothermal DSC experiments, which evidenced that the α-form is kinetically stable at temperatures lower than 25 °C. These data are of particular interest in practical applications such as spray freezing or pan coating where significant heat transfer phenomena are involved
Improvement of pharmacokinetic properties and digestive tolerability of diacerhein through solid-state modification
No full textLo scopo di questa tesi è stato principalmente quello di studiare l’interazione tra la reina e il sucralfato. Questo obiettivo è stato perseguito attraverso diversi studi di caratterizzazione al fine di valutare la fattibilità di un approccio formulativo che preveda il sequestro della reina da parte del sucralfato a livello del colon.
Il sucralfato è stato scelto come farmaco modello per il miglioramento della tollerabilità della diacereina. Le sue caratteristiche lo rendono molto promettente per contrastare l’effetto indesiderato della diacereina, sia per quanto riguarda la sua capacità di proteggere la mucosa gastrointestinale che per la sua tendenza a formare composti di interazione con diversi tipi di molecole.
Nella prima parte del lavoro sono state eseguite analisi sulle sostanze pure ed è stato allestito un metodo per studiare l’interazione tra reina e sucralfato. Gli studi in soluzione hanno prodotto campioni i quali sono stati esaminati mediante spettrofotometria UV-vis. In seguito sono state condotte analisi al fine di ottenere informazioni sulle attrazioni intermolecolari del complesso. Questo tipo di studi hanno riguardato dapprima una parte sperimentale in cui le soluzioni di interazione sono state analizzate mediante spettrofotometria UV, HPLC ed NMR in soluzione. Inoltre, sono stati condotti esperimenti d’interazione tra reina e alluminio idrossido per valutare il ruolo di quest’ultimo nell’interazione con la reina.
Infine, l’ultima parte del lavoro ha previsto la caratterizzazione dello stato solido del composto d’interazione tra le due sostanze attraverso microscopia ottica, calorimetria differenziale a scansione (DSC), diffrazione di raggi X su polvere (PXRD).The improvement of biopharmaceutical characteristics of drugs is one of the leading purpose of pharmaceutical research. Some active principles, though provided with significant therapeutical efficiency cannot be employed for their negative chemical, physical and biological features. Frequently, the most troublesome elements are the molecule solubility, permeability and dissolution rate but also its potential adverse effects. According to present technologies, it is possible to improve drugs solubility with methods more efficient than simple mechanical or chemical processes. Solid state chemistry (co-crystal production, polymorph research) and lipid or polymer–based formulations are the most promising approaches exploited to obtain an increase in solubility but also in dissolution rate of active pharmaceutical ingredients. Solubility and permeability improvement of a drug means the opportunity to reduce its daily administration dose. This feature grants a proportional decrement of adverse effects that can moreover be removed with particular technological operations. Some specific compounds can therefore protect from adverse effects when administered in association with another drug (for example non-steroideal anti-inflammatory drugs with gastro-protective molecules) or when administered by an alternative route that by-passes the area subjected to the side effects (injection of drugs or in-situ release). Side effects can also be avoided in a more specific way, by avoiding contact with the area where it performs its negative activity. This purpose is easily attained by taking advantage of the sequestrating ability of some compounds that bind active principles avoiding their undesired activity.
Diacerein is classified as a slow-acting anti-arthritic drug. It is administered by oral route and it is metabolised in rhein by enterocytes and hepatocytes before reaching the systemic circulation. Diacerein is a safe drug with a different mechanism of action with respect to non-steroideal anti-inflammatory drugs but it is not frequently used in therapy for two principal reasons: its low solubility in water and the laxative effect carried out by its metabolite, rhein, at colon level.
The improvement of biopharmaceutical characteristics and digestive tolerability of diacerein are fundamental for its safe use in therapy.
A promising technique to avoid a drug adverse effects could be carried out mimicking the procedures used in detoxifying practice, namely by identifying a molecule-specific method that could remove rhein side effect at colon level. The in situ formation of an interaction product between rhein and a binding agent would create an insoluble and/or not absorbable compound that could prevent the active ingredient side effect.
Sucralfate is a drug mainly used in therapy to treat and prevent gastric ulcer and also to protect gastro-intestinal membrane. Sucralfate has often demonstrated a good tendency to sequestrate drugs with formation of complexes. For these reasons sucralfate may be selected as candidate compound for the diacerein tolerability improvement.
In this thesis the interaction between rhein and sucralfate has been studied. This purpose has been pursued through characterization studies in order to evaluate the opportunity to produce a pharmaceutical formulation that allows the sequestration of rhein by sucralfate at colon level. Sucralfate characteristics make it a promising drug to counteract diacerein side effect at colon level where it would also exploits its mucosa-protecting action.
Analyses on raw materials have been carried out at first, then a process for rhein and sucralfate interaction study has been set up. Molecular interactions between the two drugs have been studied in solution by means of Uv-vis spectroscopy, HPLC and 1H-NMR. Experiments between rhein and aluminium hydroxide have also been conducted to evaluate the role of this moiety in the interaction process between sucralfate and rhein. Solid-state characterization has moreover been carried out to investigate the solid compound obtained from rhein and sucralfate interaction. Optical microscopy, differential scanning calorimetry and powder X-ray diffraction contributed to define the profile of the interaction product.
The results collected in this thesis describe a complex pattern for rhein and sucralfate interaction. Data indicate that the two drugs interact in solution giving rise to a complex. In particular, Uv-vis spectra and solution 1H-NMR analysis provides clear evidences of the formation of said complex. The solubility of the interaction compound remains an issue that the present experimentation has not completely addressed. As a matter of fact, most studies underline the formation of an insoluble complex. Nevertheless there are some experimental evidences that support the opposed hypothesis, namely the formation of a soluble compound that subtract rhein from the detection of the analytical instrumentation. In this case the product obtained reveals a stoichiometry of one mole of rhein for two moles of sucralfate in concentrated solutions. Sucralfate content increase for more diluted solutions. Another hypothesis can be considered, that is the formation of a solid solution between sucralfate and the interaction compound.
The solid phase isolated from the two ingredients interaction reveals an amorphous and glassy structure.
The initial hypothesis to exploit in therapy the interaction between rhein and sucralfate, remains in any case valid to reduce the heavy side effects of rhein. The preparation of an oral pharmaceutical formulation with appropriate delivery kinetics would permit a safe use of diacerein in therapy with the complete removal of its major and more problematic side effect. This approach has however to be confirmed with an in vivo study.embargoed_2013060
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
Improvement of pharmacokinetic properties and digestive tolerability of diacerhein through solid-state modification
No full textLo scopo di questa tesi è stato principalmente quello di studiare l’interazione tra la reina e il sucralfato. Questo obiettivo è stato perseguito attraverso diversi studi di caratterizzazione al fine di valutare la fattibilità di un approccio formulativo che preveda il sequestro della reina da parte del sucralfato a livello del colon.
Il sucralfato è stato scelto come farmaco modello per il miglioramento della tollerabilità della diacereina. Le sue caratteristiche lo rendono molto promettente per contrastare l’effetto indesiderato della diacereina, sia per quanto riguarda la sua capacità di proteggere la mucosa gastrointestinale che per la sua tendenza a formare composti di interazione con diversi tipi di molecole.
Nella prima parte del lavoro sono state eseguite analisi sulle sostanze pure ed è stato allestito un metodo per studiare l’interazione tra reina e sucralfato. Gli studi in soluzione hanno prodotto campioni i quali sono stati esaminati mediante spettrofotometria UV-vis. In seguito sono state condotte analisi al fine di ottenere informazioni sulle attrazioni intermolecolari del complesso. Questo tipo di studi hanno riguardato dapprima una parte sperimentale in cui le soluzioni di interazione sono state analizzate mediante spettrofotometria UV, HPLC ed NMR in soluzione. Inoltre, sono stati condotti esperimenti d’interazione tra reina e alluminio idrossido per valutare il ruolo di quest’ultimo nell’interazione con la reina.
Infine, l’ultima parte del lavoro ha previsto la caratterizzazione dello stato solido del composto d’interazione tra le due sostanze attraverso microscopia ottica, calorimetria differenziale a scansione (DSC), diffrazione di raggi X su polvere (PXRD).The improvement of biopharmaceutical characteristics of drugs is one of the leading purpose of pharmaceutical research. Some active principles, though provided with significant therapeutical efficiency cannot be employed for their negative chemical, physical and biological features. Frequently, the most troublesome elements are the molecule solubility, permeability and dissolution rate but also its potential adverse effects. According to present technologies, it is possible to improve drugs solubility with methods more efficient than simple mechanical or chemical processes. Solid state chemistry (co-crystal production, polymorph research) and lipid or polymer–based formulations are the most promising approaches exploited to obtain an increase in solubility but also in dissolution rate of active pharmaceutical ingredients. Solubility and permeability improvement of a drug means the opportunity to reduce its daily administration dose. This feature grants a proportional decrement of adverse effects that can moreover be removed with particular technological operations. Some specific compounds can therefore protect from adverse effects when administered in association with another drug (for example non-steroideal anti-inflammatory drugs with gastro-protective molecules) or when administered by an alternative route that by-passes the area subjected to the side effects (injection of drugs or in-situ release). Side effects can also be avoided in a more specific way, by avoiding contact with the area where it performs its negative activity. This purpose is easily attained by taking advantage of the sequestrating ability of some compounds that bind active principles avoiding their undesired activity.
Diacerein is classified as a slow-acting anti-arthritic drug. It is administered by oral route and it is metabolised in rhein by enterocytes and hepatocytes before reaching the systemic circulation. Diacerein is a safe drug with a different mechanism of action with respect to non-steroideal anti-inflammatory drugs but it is not frequently used in therapy for two principal reasons: its low solubility in water and the laxative effect carried out by its metabolite, rhein, at colon level.
The improvement of biopharmaceutical characteristics and digestive tolerability of diacerein are fundamental for its safe use in therapy.
A promising technique to avoid a drug adverse effects could be carried out mimicking the procedures used in detoxifying practice, namely by identifying a molecule-specific method that could remove rhein side effect at colon level. The in situ formation of an interaction product between rhein and a binding agent would create an insoluble and/or not absorbable compound that could prevent the active ingredient side effect.
Sucralfate is a drug mainly used in therapy to treat and prevent gastric ulcer and also to protect gastro-intestinal membrane. Sucralfate has often demonstrated a good tendency to sequestrate drugs with formation of complexes. For these reasons sucralfate may be selected as candidate compound for the diacerein tolerability improvement.
In this thesis the interaction between rhein and sucralfate has been studied. This purpose has been pursued through characterization studies in order to evaluate the opportunity to produce a pharmaceutical formulation that allows the sequestration of rhein by sucralfate at colon level. Sucralfate characteristics make it a promising drug to counteract diacerein side effect at colon level where it would also exploits its mucosa-protecting action.
Analyses on raw materials have been carried out at first, then a process for rhein and sucralfate interaction study has been set up. Molecular interactions between the two drugs have been studied in solution by means of Uv-vis spectroscopy, HPLC and 1H-NMR. Experiments between rhein and aluminium hydroxide have also been conducted to evaluate the role of this moiety in the interaction process between sucralfate and rhein. Solid-state characterization has moreover been carried out to investigate the solid compound obtained from rhein and sucralfate interaction. Optical microscopy, differential scanning calorimetry and powder X-ray diffraction contributed to define the profile of the interaction product.
The results collected in this thesis describe a complex pattern for rhein and sucralfate interaction. Data indicate that the two drugs interact in solution giving rise to a complex. In particular, Uv-vis spectra and solution 1H-NMR analysis provides clear evidences of the formation of said complex. The solubility of the interaction compound remains an issue that the present experimentation has not completely addressed. As a matter of fact, most studies underline the formation of an insoluble complex. Nevertheless there are some experimental evidences that support the opposed hypothesis, namely the formation of a soluble compound that subtract rhein from the detection of the analytical instrumentation. In this case the product obtained reveals a stoichiometry of one mole of rhein for two moles of sucralfate in concentrated solutions. Sucralfate content increase for more diluted solutions. Another hypothesis can be considered, that is the formation of a solid solution between sucralfate and the interaction compound.
The solid phase isolated from the two ingredients interaction reveals an amorphous and glassy structure.
The initial hypothesis to exploit in therapy the interaction between rhein and sucralfate, remains in any case valid to reduce the heavy side effects of rhein. The preparation of an oral pharmaceutical formulation with appropriate delivery kinetics would permit a safe use of diacerein in therapy with the complete removal of its major and more problematic side effect. This approach has however to be confirmed with an in vivo study
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
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