1,721,170 research outputs found
«Ad imitatione, e somiglianza di quello che v'era anticamente»: il restauro dell'abside di S. Giovanni in Laterano a Roma al tempo di Nicola IV (1288-1292)
Full text linkProcess intensification of the polishing step of a bioactive peptide through Multicolumn Countercurrent Solvent Gradient Purification
No full textPharmaceutical products, including peptides, must satisfy very strict purity specifications, because of quality and safety reasons. Therefore, the necessity to operate one or more purification steps to obtain high quality drugs is indisputable. Critical impurities chemically very similar to the target product are generated during the synthesis and are generally removed by means of preparative single-column chromatographic techniques (=batch methods) [1,2]. Batch methods struggle to separate completely the peptide of interest from other groups of impurities, because of their similarity and of high loading of sample processed in preparative conditions, which cause peaks overlapping [3]. The typical situation encountered in these cases is the so-called center-cut separation, where the target elutes as intermediate between two other groups of impurities less and more retained respectively. The direct consequence of this apparently insurmountable overlapping is a yield-purity trade-off, a limit intrinsic to batch chromatography according to which it is possible to obtain either high purity or high recovery of the peptide of interest, depending on whether the overlapping windows are collected or not [4]. This trade-off leads to drawbacks in the overall economy of the process. Multicolumn chromatographic processes, operating in continuous and countercurrent mode, can alleviate this limitation by performing internal recycling of the overlapping portions of the chromatogram [5]. The technique used in the frame of this research is twin-column Multicolumn Countercurrent Solvent Gradient Purification (MCSGP), which has been applied to the purification of an industrial crude of a bioactive decapeptide. It has been demonstrated that MCSGP leads to promising results, including a remarkable improvement in process performance (up to 6 times higher) from the point of view of recovery, productivity and solvent consumption, with respect to the corresponding batch run. The automation of the process on industrial scale would lead to great reproducibility which would reflect in improved consistency in product quality.
References
[1] De Luca, C.; Felletti, S.; Lievore, G.; Buratti, A.; Vogg, S.; Morbidelli, M.; Cavazzini, A.; Catani, M.; Macis, M.; Ricci, A.; Cabri, W. J Chromatogr A 2020, 1625, 1-7.
[2] De Luca, C.; Felletti, S.; Lievore, G.; Chenet, T.; Morbidelli, M.; Sponchioni, M.; Cavazzini, A.; Catani, M. Trends Analyt Chem 2020, 132, 1-8.
[3] Vogg, S.; Ulmer, N.; Souquet, J.; Broly, H.; Morbidelli, M. Biotechnol J 2019, 1800732, 1-8.
[4] Müller-Späth, T.; Ströhlein, G.; Lyngberg, O.; Maclean, D. Chem Today 2013, 31, 56-60.
[5] Steinebach, F.; Müller-Späth, T.; Morbidelli, M. Biotechnol J 2016, 11, 1126-1141
Experimental and Modeling Study of Acrylamide Copolymerization with Quaternary Ammonium Salt in Aqueous Solution
No full textThe free-radical copolymerization of acrylamide with the cationic monomer DMAEA-Q in aqueous medium is investigated with special attention to its composition behavior, which reveals to be affected by the electrostatic interactions between the charges in the system. The reaction kinetics is determined by in situ 1H NMR experiments, showing a peculiar dependence of the copolymer composition upon initial monomer and electrolyte concentrations. A kinetic model simulating the evolution of copolymer composition as a function of conversion is developed, accounting for the nonconventional features of the system. Namely, a description of the electrostatic interactions based on the DLVO theory is introduced to define a functional dependence of the rate coefficients on the ionic strength. Secondary reactions are also included due to the acrylic nature of both monomers. The proposed model is applied to estimate the corresponding reactivity ratios and proves to exhibit the correct functionality with respect to monomer concentration and ionic strength. (Figure Presented)
Design space and robustness analysis of batch and counter-current frontal chromatography processes for the removal of antibody aggregates
No full textIncreasing molecular diversity and market competition requires biopharmaceutical manufacturers to intensify their processes. In this respect, frontal chromatography on cation exchange resins has shown its potential to effectively remove aggregates. However, yield losses during the wash step need to be accepted in order to ensure robust product quality. In this work, we present a novel counter-current frontal chromatography process called Flow2, which uses inline dilution during an interconnected wash phase to allow high monomer recovery without contaminating the product pool with impurities. Its model-based design spaces under purity and yield constraints are compared with those corresponding to traditional batch processes in terms of size and process attributes yield and productivity. The Flow2 process shows the largest extent of feasible operating points independent of feed conditions. Thereby, it allows the implementation of higher ionic strength wash, thus widening the range of operating conditions resulting in yields above 95% compared to batch processes. Productivities of batch and counter-current processes are the same at short regeneration times and equal residence time. However, long regeneration times, while influencing the size of the Flow2 design space, are not detrimental for its productivity resulting in twice as high values as obtained for the batch process. Furthermore, process robustness is evaluated by the ability of the process to maintain the required product quality when subjected to process parameter perturbations. It is found that the Flow2 process is able to retain a larger design space associated also with higher yields showing its ability to improve process attributes without sacrificing robustness at the same time
New Trend in polymer reaction engineering
No full textSome among the recent developments in polymer reaction engineering are briefly reported. To this aim, selected examples from Authors’ experience are used instead of attempting an exhaustive overview. In the first section, a detailed model of emulsion copolymerization is used to evaluate the distributions of molecular weights and chain ends of a fluorinated polymer. Then, the important phenomenon of particle coagulation in dispersed polymerizations is addressed and the results of a few illustrative calculations are discussed. As new processes (second section), living free-radical polymerizations, those in supercritical carbon dioxide and frontal polymerizations are presented. Comments about the potential of these processes with respect to industrially attractive applications are reported. Finally, process monitoring and control, essential items of all industrial polymerization processes, are examined in the third section. The capabilities of different sensors, suitable to be applied to both homogeneous and heterogeneous processes, are reviewed along with applications of polymer quality control
Integration and digitalization in the manufacturing of therapeutic proteins
No full textThe biopharmaceutical market has experienced a tremendous growth in the last years. However, this growth should be balanced considering the difficulty in bioproduct development and the associated high manufacturing costs. These limitations are pushing towards process intensification, stimulated by the Quality by Design (QbD) initiative. Integrated continuous biomanufacturing has emerged as a promising approach towards high throughputs and reliable product quality attributes. At the same time, to face the increased management complexity and compensate fluctuations at the level of the different unit operations, model-based digitalization stands as a fundamental element. In this review, we discuss the state of the art in integrated biomanufacturing and digitalization to highlight their potential towards process intensification. The continuous technologies adopted in the upstream and downstream processing are first reviewed, with a focus on perfusion bioreactors and continuous chromatography. Then, model-based digitalization and its potential in the monitoring and control of integrated bioprocesses are discussed
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
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