1,721,008 research outputs found
Aspects of diclofenac salts affecting the release from solid dosage forms
No full textThe formation of pharmaceutical salts is widely recognized as a tool to improve the solubility in water of many acidic or basic drugs. This is also the case of diclofenac, an important member of non steroidal anti-inflammatory drug class, whose low solubility in water suggested formulations in the form of sodium and potassium salt, for oral delivery, and of diethylamine and N-pyrrolidine ethanol salts for topical applications. To support the idea that solubility is still an intriguing problem for diclofenac there is the number of paper in the scientific literature concerning the preparation and the physico-chemical determinations of many new diclofenac salts.
In this communication we present a study of the solid state of some diclofenac salts, as a starting point to discuss and interpret their solubility values and their behavior to the release from solid dosage forms.
Diclofenac is poorly soluble in water since in the solid state it exists as dimmers, bound together with a network of hydrogen bonding, involving the carboxylic groups. This way the hydrophilic moieties are kept far from interaction with the dissolution medium by the hydrophobic portions of the molecule. These hydrogen bonds are destroyed by increasing pH or by the formation of a salt form.
Salts of alkaline metals are hydrate, but usually marketed as de-hydrate form; these are not stable since recover their water crystallization molecules, if not adequately protected. Their solubility in water is not so high as that of other sodium or potassium NSAID salts, but their behavior in water solution suggests that the diclofenac anions self-aggregate forming micelle-like forming systems, but with limited solubilisation ability.
Salts formed with hydroxy aliphatic amines, despite the hydrophilic contribution of increasing number of hydroxy groups do not form hydrate, when prepared from water and have limited solubility in water. The nature of their solid state explains this behavior, since these salts exist as ion-pairs, where hydroxy groups of each cation are strictly hydrogen bonded with the corresponding diclofenac anion: this structure in most cases originates high melting point and reduce solubility.
Salts formed with volatile amine have a narrow range of stability with temperature and experiment dissociation even at low temperature, during drying process, that leaves the parent acidic diclofenac, while the low-boiling amine is lost as vapor.
Finally the most interesting compound of this group is represented by diclofenac/N-pyrrolidine ethanol salt, which forms a polymorph hydrate and displays a complex behavior as a function of RU, temperature and pressure; moreover its aqueous solution display solubilisation ability towards hydrophobic substances above 35 mM.
As a conclusion it can be suggested that pharmaceutical salts offer a chemical form suitable to improve solubility and dissolution rate, and thus availability of an active agent, provided that the structure of the solid state of the salts does not originate unforeseen adverse problems, such as in the case of the particular molecular structure of diclofenac and ensure sufficient stability for their handling
SupplementaryMaterial_EP - Human Foragers: Searchers by Nature and Experience
No full textSupplementaryMaterial_EP for Human Foragers: Searchers by Nature and Experience by César Maya, Marcos F. Rosetti, Luis Pacheco-Cobos and Robyn Hudson in Evolutionary Psychology</p
Pharmaceutical Salts
No full textMost drugs are formulated, when possible, as salts, for their better technological parameters, such as solubility, handling, stability, crystallinity, etc. However this modification of the chemical form, beside many advantages, originates in turn a series of problems, such as formation of hydrates, polimorphs, thermal instability, in the solid state; and/or hydrolysis, acid-base equilibrium, etc. in solution, which limit their applications.
The choice of the optimum salt forming agent for a given molecule is a problem not yet solved and is left to the sensitivity of the experimenter, as well as well the selection of a salt to improve a given parameter. From this point of view sodium salt, for acidic drugs, and hydrochloride, for basic drugs, represent the first choice, even though in the pharmaceutical market, different salts are present and many of them without being approved by FDA. An increased number of aliphatic amines are used to form salt with NSAID, opening new applications (e.g. absorption of the active principle via ion-pairs) or troubles for the taste or volatility of the bases.
The main advantage deriving from the formation of a salt is the improvement of the solubility in water: most of acidic drugs form a dimer in the solid state, where the carboxyl groups face together by hydrogen bonds, preventing thus the hydrophilic portion to interact with water. This structure is destroyed by an increase of pH or the formation of the ionic structure of a salt. Diffractometric examination of the salt crystals can highlight the intimate structure of the compound, useful to interpret its behavior.
A salt, with respect to the acidic parent drug, offers a better solubility and dissolution rate, provided that this chemical form is prevented to come into contact with the acidic gastric environment after its oral administration. However even in the case of destruction of the salt form in acidic medium, the drug precipitates in particles of very small size, guaranteeing a prompt dissolution when pH turns favorable. Not always the use of hydroxy organic bases, as salt forming agents, improving hydrophilicity of the salt, improves its solubility, since the promotion of hydrogen bonds in the solid state between anion and cation represents an unforeseen increase of the melting point and therefore decrease of solubility of the salt. In some case a depressed solubility is looked for depressed by the formation of a salt with heavy metal cation (e.g. calcium) for stability problem or for a masked taste.
Many salts form hydrates, including water molecules into the crystal lattice. Thermal and thermogravimetric analysis are necessary to evidence the stoichiometry of the salt. In these cases the question is: which is the most stable or useful form, the one hydrate or the other one de-hydrated on heating? Dehydration can be accompanied by the formation of amorphous structures or thermal instability. Storage in controlled relative humidity is necessary in each case.
All the situations reported above, which are rather general for pharmaceutical salts, were found studying the properties of the salts of the non-steroidal anti-inflammatory drug diclofenac, and represent the results of our most recent research
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
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