1,720,981 research outputs found
Greening the downstream of biopharmaceuticals through process intensification in the research on innovative eco-compatible solvent
No full textBiopharmaceuticals are becoming increasingly important as therapeutic treatment, due to their unique characteristics that cannot be replicated by conventional drugs. They are used for treating symptoms associated with various diseases, including cancer and metabolic diseases. The synthesis of peptides involves the use of various methods, all of which produce not only the target active pharmaceutical ingredient (API) but also different types of impurities [1]. Since strict purity standards must be adhered to in order to commercialize the peptide for pharmaceutical scopes, a downstream process is very often necessary. In recent years, there has been a growing awareness of environmental issues, leading to a focus on sustainable practices in various industries, including (bio)pharmaceutical ones. Analytical methods, particularly liquid chromatography (LC), contribute to chemical waste production, and the pharmaceutical industry is actively seeking greener alternatives [2]–[4]. The use of solvents, a significant aspect of chemical processes, is highlighted in the 12 principles of Green Analytical Chemistry (GAC), emphasizing the need for safe and eco-friendly alternatives. Pharmaceutical companies, such as Pfizer, AstraZeneca, and GlaxoSmithKline, have developed solvent selection guides based on criteria like safety, health, environmental impact, and cost. The focus is on the minimization of environmental impact besides increasing production efficiency. Pharmaceutical peptides are usually purified in reversed-phase preparative liquid chromatography (RP-HPLC) that involves the use of an apolar stationary phase and a polar mobile phase, usually consisting of a mixture of water and an organic modifier. Acetonitrile (ACN) has always been the preferred choice for its characteristics (good miscibility in water, excellent strength elution, etc.) but it is toxic to environmental and human health. Ethanol, isopropanol, acetone, ethyl lactate, and propylene carbonate are identified as greener alternatives, but they have some limitations. Other less popular solvents are also gaining attention in particular by looking at their reduced eco-toxicity and biodegradability [5]. In downstream processes, the replacement of toxic solvents is crucial, and alternatives like formic acid and acetic acid are considered more sustainable than trifluoroacetic acid (TFA). Quaternary ammonium salts with phosphate counterions are emerging alternatives in mobile phases. Continuous chromatographic techniques are explored as eco-friendly options, with the aim of overcoming the purity-performance trade-off in biopharmaceutical production. Therefore, the environmental impact of downstream processing could be potentially reduced by means of different ways. In this thesis two of them will be discussed. The first one is the replacement of acetonitrile with alternative greener solvents (e.g., alcohols) [2]. Another approach is the employment of multi-column continuous chromatography, which is based on the internal recycling of portions of the chromatogram, thus allowing for a reduction in solvent consumption with respect to corresponding single-column processes [6]. This thesis will show, through a series of case studies, how it is possible to reduce the environmental impact of purification approaches by using both alternative solvents to ACN and multicolumn continuous approaches.I biofarmaci stanno diventando sempre più importanti come trattamento terapeutico, grazie alle loro caratteristiche uniche che non possono essere replicate dai farmaci convenzionali. Sono utilizzati per trattare i sintomi associati a varie malattie, tra cui il cancro e le malattie metaboliche. La sintesi dei peptidi coinvolge l'uso di vari metodi, tutti i quali producono non solo il principio attivo farmaceutico (API) di destinazione ma anche diversi tipi di impurezze [1]. Poiché è necessario attenersi a rigorosi standard di purezza per commercializzare il peptide per scopi farmaceutici, è spesso necessario un processo di purificazione. Negli ultimi anni, c'è stata una crescente consapevolezza delle questioni ambientali, portando a un focus sulle pratiche sostenibili in vari settori, compresi quelli (bio)farmaceutici. I metodi analitici, in particolare la cromatografia liquida (LC), contribuiscono alla produzione di rifiuti chimici, e l'industria farmaceutica sta cercando attivamente alternative più ecologiche [2], [3], [4]. L'uso di solventi, un aspetto significativo dei processi chimici, è evidenziato nei 12 principi della Chimica Analitica Verde (GAC), sottolineando la necessità di alternative sicure ed eco-friendly. Le aziende farmaceutiche, come Pfizer, AstraZeneca e GlaxoSmithKline, hanno sviluppato guide alla selezione dei solventi basate su criteri come sicurezza, salute, impatto ambientale e costo. L'attenzione è rivolta alla minimizzazione dell'impatto ambientale oltre all'aumento dell'efficienza produttiva. I peptidi farmaceutici sono di solito purificati mediante cromatografia liquida preparativa a fase inversa (RP- HPLC) che comporta l'uso di una fase stazionaria apolare e di una fase mobile polare, di solito costituita da una miscela di acqua e un modificatore organico. L'acetonitrile (ACN) è sempre stato la scelta preferita per le sue caratteristiche (buona miscibilità in acqua, ottima eluizione di forza, ecc.) ma è tossico per l'ambiente e la salute umana. L'etanolo, l'isopropanolo, l'acetone, il lattato di etile e il carbonato di propilene sono identificati come alternative più ecologiche, ma hanno alcuni limiti. Altri solventi meno popolari stanno guadagnando attenzione in particolare guardando alla loro minor ecotossicità e biodegradabilità [5]. Nei processi di purificazione, la sostituzione di solventi tossici è cruciale, e alternative come l'acido formico e l'acido acetico sono considerate più sostenibili del trifluoroacetico (TFA). I sali di ammonio quaternario con contro ioni fosfato stanno emergendo come alternative nelle fasi mobili. Le tecniche cromatografiche continue sono esplorate come opzioni eco- friendly, con l'obiettivo di superare il compromesso tra purezza e prestazioni nella produzione di biofarmaci. Pertanto, l'impatto ambientale del processo di downstream potrebbe essere potenzialmente ridotto mediante diversi modi. In questa tesi se ne discuteranno due. Il primo è la sostituzione dell'acetonitrile con solventi più ecologici alternativi (ad esempio, alcoli) [2]. Un altro approccio è l'impiego della cromatografia continua multicolonna, basata sul riciclo interno di porzioni del cromatogramma, consentendo così una riduzione del consumo di solvente rispetto ai processi a colonna singola corrispondenti [6]. Questa tesi mostrerà, attraverso una serie di studi di caso, come sia possibile ridurre l'impatto ambientale degli approcci di purificazione utilizzando sia solventi alternativi all'ACN che approcci continui multicolonna
Recent developments in the high-throughput separation of biologically active chiral compounds via high performance liquid chromatography
No full textBioactive compounds, including active pharmaceutical ingredients (APIs), are often chiral molecules where stereoisomers have different biological and therapeutic activity. Nevertheless, the preparation of these molecules can lead to racemic or scalemic mixtures (it is not trivial to produce just the optically pure compound). The evaluation of the enantiomeric purity of bioactive compounds, and therefore quality, is indeed of fundamental importance for regulatory scopes. Chiral high performance liquid chromatography (HPLC) is the gold standard technique to separate and to purify enantiomers. This comes from the wide availability of commercial chiral stationary phases (CSPs) and operational modes, which makes the technique extremely versatile. In recent years, the most relevant trend in the field of chiral analytical HPLC has been the development of CSPs suitable for fast or even ultrafast separations, thus favoring the high throughput screening of biologically active chiral compounds. This process has somehow lagged behind compared to achiral HPLC, due to a series of practical and fundamental issues. The experience has shown how in chiral chromatography even very basic concepts, such as the supposed kinetic superiority of core-shell (pellicular) particles over fully porous ones to improve the chromatographic efficiency, cannot be taken for granted. In this review, the most relevant fundamental and practical features that must be taken into consideration to design successful high-throughput, fast enantioseparations will be discussed. Afterwards, the main classes of CSPs and the most relevant, recent (last five-year) high-throughput applications in the field of the separation of chiral bioactive compounds (for pharmaceutical, forensic, food, and omics applications) will be considered
Integrated multidimensional chromatography on preparative scale for oligonucleotides purification
No full textTherapeutic oligonucleotides represent a recent breakthrough in the pharmaceutical industry due to their ability to regulate gene expression with great specificity. This aspect allows treatment of a wide range of diseases. However, since oligonucleotides are used for therapeutic purposes, the Active Pharmaceutical Ingredient (API) must fulfill strict purity levels which require intensive purification steps. For oligonucleotides, and biomolecules in general, preparative liquid chromatography is the technique of choice to perform large scale purifications, typically in batch mode, i.e. using a single column. Specifically, since ONs are mainly large, hydrophilic and charged molecules, Anion Exchange chromatography (AEX) and Ion Pair Reversed Phase chromatography (IPRP) are the preferred chromatographic modes for their downstream processing. Nevertheless, these approaches suffer from a purity-yield trade-off, and for this reason, more than one purification step is usually required. The two chromatographic modes can therefore be used consequently to remove different groups of impurities, thanks to their orthogonality. In this work, a multidimensional and orthogonal approach on a (semi)preparative scale, namely "Integrated Batch process", was applied for the purification of a single-stranded DNA oligonucleotide. This process combines two chromatographic steps without any hold step, operator intervention or sampling of the first step. The performance parameters of the Integrated Batch were compared to those obtained in the single batch runs under different experimental conditions (chromatographic mode, eluent systems), showing the potential of this integrated approach. This proof-of-concept study illustrates how this technique can considerably reduce overall production time and how it allows to increase the robustness and reproducibility of the method, since the process is highly automated
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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