1,720,979 research outputs found
Screening for new pharmaceutical solid forms using mechanochemistry: A practical guide
No full textThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Within the pharmaceutical industry, and elsewhere, the screening for newsolid forms is a mandatory exercise for both existing and new chemical entities. This contribution focuses on mechanochemistry as a versatile approach for discovering new and alternative solid forms. Whilst a series of recently published extensive reviews exist which focus on mechanistic aspects and potential areas of development, in this review we focus on particular practical aspects of mechanochemistry in order to allow full optimisation of the approach in searches for new solid forms including polymorphs, salts and cocrystals as well as their solvated/hydrated analogues. As a consequence of the apparent experimental simplicity of the method (compared to more traditional protocols e.g. solvent-
based methods), the high efficiency and range of conditions available in a mechanochemical screen, mechanochemistry should not be considered simply as an alternative method when other screening methods are not successful, but rather as a key strategy in any fully effective solid form screen providing reduced effort and time as well as the potential of requiring reduced amounts of material
Better and greener: sustainable pharmaceutical manufacturing technologies for highly bioavailable solid dosage forms
Full text linkIn the last decades, Green Chemistry has been gaining widespread attention within the pharmaceutical field. It is thus very important to bring more sustainable approaches into the design and manufacture of effective oral drug delivery systems. This review focuses on spray congealing and mechanochemical activation, two technologies endorsing different principles of green chemistry, and at the same time, addressing some of the challenges related to the transformation of poorly water-soluble drugs in highly bioavailable solid dosage forms. We therefore present an overview of the basic principles, equipment, and application of these particle-engineering technologies, with specific attention to case studies carried out by the groups working in Italian Universities. Graphical abstract: [Figure not available: see fulltext.
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
Mechanochemical Synthesis of Multicomponent Crystals: One Liquid for One Polymorph? A Myth to Dispel
Full text linkIdentifying as many polymorphs as possible for a molecular compound is important in the design of materials with desired properties. In this paper we demonstrate, using a simple experimental procedure, how the amount of liquid present during liquid-assisted mechanochemical reactions can be used to rapidly explore polymorph diversity. Through detailed experimental evidence it is concluded that for the specific (multicomponent) crystal system investigated (caffeine–anthranilic acid) the commonly accepted rule “one liquid for one specific polymorph” is not correct. Additionally we demonstrate that through modification of the amount of added liquid it is possible to form a polymorph previously obtained only by a desolvation reaction. We believe that while the results raise many mechanistic questions the approach is advantageous as a means of rapidly screening for polymorph diversity as well as being a simple screening methodology. While we focus here on a cocrystal system, we believe a similar approach will be advantageous for single component systems
Polymer-Assisted Grinding, a Versatile Method for Polymorph Control of Cocrystallization
No full textDespite the great interest that cocrystals
are currently gaining
for their application to the design of new supramolecular structures
with desired functional properties, studies concerning new experimental
strategies capable of controlling polymorphism phenomena of a given
system are scarcely reported. We propose herein the use of polymer-assisted
grinding (POLAG) as a new method for the selective control of the
product polymorphic form in a mechanochemical cocrystallization reaction.
Specifically, to the model system selected in this study formed by
caffeine and glutaric acid, we demonstrate that the polymorphic outcome
can be controlled by modifying the number of monomer units of the
catalyst from the shortest dimer to a polymer with chains of approximately
1000 units. The characteristics of each polymorphic form were investigated
by low-dose high-resolution TEM, and the mechanistic aspects of the
cocrystal formation were studied through a series of ex situ and interconversion
experiments. The results suggest that for this system the modification
of the catalyst chain length and, consequently, modification of polarity
drives cocrystal formation toward the more stable polymorph. The approach
proposed in this paper can be readily applied to each system, where
polarity is the main issue for polymorph control without the risk
of solvate formation
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
Development and pharmacokinetic evaluation of erythromycin lipidic formulations for oral administration in rainbow trout (Oncorhynchus mykiss)
No full textThe aim of this work was to enhance the bioavailability of erythromycin base when administered orally
in rainbow trout (Oncorhynchus mykiss). Since erythromycin is normally given in the form of medicated
feed, in this study three new types of feed formulation were developed. A self-emulsifying system and
two types of double microemulsions (O/W/O) were prepared, characterized and adsorbed on a commercial
extruded diet for fish. The emulsified systems were based on saturated polyglycolized glycerides and
mono- and diglycerides of medium-chain fatty acids (as oily phase), Tween 80 (as surfactant) and, in the
case of double microemulsions, distilled water. The systems differed in percentage composition and for
the amount and position of erythromycin in different phases. The three medicated feed were then administered
orally by means of a gastric probe to rainbow trout and their relative bioavailability was estimated
in comparison with that obtained after oral administration of feed with erythromycin powder.
For each medicated feed, 80 fish were tested. Finally, plasma profiles of erythromycin after single administration
of medicated feeds were used to predict profiles obtainable by administering once-daily medicated
feeds for 7 consecutive days. The results proved that the feeds containing microemulsified
erythromycin provided largely superior oral bioavailability and the advantage of obtaining the same efficacy
against bacterial infections with a much lower dose of drug
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
Mechanochemical Formation and "disappearance" of Caffeine-Citric-Acid Cocrystal Polymorphs
No full textThe inability to obtain a crystal form that has previously been reliably prepared is an important concern for industrial solid-state scientists. In the present study, we extend further the evidence that such a phenomenon also applies to cocrystals. Specifically, we report further on the apparent "disappearing polymorphs" of a cocrystal composed of caffeine and citric acid. This study commenced at the University of Cambridge with the initial aim of gaining insight into the mechanisms associated with the mechanochemical formation of the known caffeine-citric-acid cocrystal, namely, Form I. A second polymorph, Form II, was later prepared mechanochemically through neat grinding, making it seemingly impossible to reproduce Form I in the same laboratory. Subsequent studies also resulted in the mechanochemical formation of another polymorph, Form III, for which no structural characterization has yet been possible. We therefore also focus on the understanding of the factors contributing to the inability to reproduce Form I after another polymorph has been obtained. Experiments were then extended to two other laboratories within different UK universities (De Montfort University Leicester and University College London) and revealed that, depending on the "apparent" level of contamination of a specific laboratory, different polymorphs can be obtained, but only one of them at any period of time. The inability to predict, control, and understand disappearing polymorphs remains a frustrating experience - even 25 years after Dunitz and Bernstein first stated that "we are far from being able to present a theory of disappearing polymorphs". In this context, we reason that a first step forward would consist of reporting comprehensive and detailed accounts for every example of apparently disappearing polymorphs, with the hope of finding similarities that can subsequently result in a better understanding and possible rationalization of the puzzling phenomenon of disappearing polymorphs. We here report what we know so far of the intriguing caffeine-citric-acid cocrystal system
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