Batch and continuous blending of particulate material studied by near-infrared spectroscopy

Background: Pharmaceutical manufacturing is moving towards real-time release of the products. This objective can only be achieved by clearly understanding the process and by implementing suitable technologies for manufacturing and for process control. Near-infrared (NIR) spectroscopy is one technology that has attracted lot of attention from the pharmaceutical industry since it can analyze bulk solids without any pretreatment, therefore reducing or eliminating wet chemistry analysis. NIR spectroscopy is a powerful tool for the monitoring unit operations were bulk material is involved i.e. blending of powders. Blending of powders is a complex and poorly understood unit operation. In the pharmaceutical industry blending has been performed batchwise and controlled by thief sampling. Thief sampling is an invasive process which is tedious and tends to introduce bias; therefore an alternative sampling method was highly needed. Here is where NIR found a perfect match with blend uniformity monitoring, thus NIR implementation offers several advantages: thief sampling is avoided, the process is continuously monitored, detection of blend-end point, and fast identification of process deviations. NIR spectral data need to be correlated with the parameter of interest (physical or chemical). These computations are done by multivariate data analysis (MVDA). MVDA and NIR are a powerful combination for in-process control and their use has been promoted by the health authorities through the Process Analytical technology (PAT) initiative by the FDA. Purpose: This thesis is focused on the study of powder blending, which is an essential unit operation for the manufacture of solid dosage forms. The aim was to develop two quantitative methods for the monitoring of the active ingredient concentration. One method was developed for blend uniformity monitoring of a batch mixing process, and a second method for a continuous mixing process. This study also tackles the relevance of the physical presentation of the powder on the final blend quality, by studying the influence of the particle size and the effect of the previous manufacturing steps on the NIR spectral data. Methods: Particle size was studied by NIR in diffuse reflectance mode, using Kubelka-Munk function and the transformation of reflectance of absorbance values, in order to focus the analysis on the physical properties. Furthermore, an off-line NIR model was developed for the quantification of the mean particle size. Segregation tendencies due to particle size incompatibilities were studied. Blend uniformity monitoring of a batch pharmaceutical mixing was achieved through a NIR off- line calibration method, which was used for the in-line drug quantification of a production scale mixing process. NIR in diffuse reflectance mode was used in the study of a continuous blending system. The effect of the process parameters, i.e. flow rate and stirring rate, was analyzed. Moreover, a NIR method for the in-line drug quantification was developed. NIR was implemented in a powder stream, in which the mass of powder measured by NIR was estimated. Results and discussion: Regarding particle size, incompatibilities due to different particle size ranges between the formulation ingredients lead to severe segregation. Particle size and cohesion determined the quality of the powder blend; slight cohesion and broader particle size distribution improved the robustness of the final blend. NIR showed high sensitivity to particle size variations, thus it was possible to develop a quantitative model for the mean particle size determination with a prediction error of 16 micrometers. Concerning batch mixing, an off-line calibration was generated for the quantification of two active ingredients contained in the formulation. The prediction errors varied from 0.4 to 2.3% m/m for each of the drugs respectively. Special emphasis was given on the proper wavelength selection for the quantitative analysis in order to focus the analysis on the active ingredients quantification. In relation to continuous blending of particulate material, a quantitative NIR model was developed for the in-line prediction of the active ingredient concentration. The NIR model was tested under different process conditions of feeding rate and stirring rate. High stirring rates produce higher scattering of the NIR predictions. This was directly associated with the acceleration of the particles at the outlet of the blender affecting the dwell time of the particles with the NIR probe. The NIR model showed to be robust to moderate feed rate increments; however the NIR model under-predicted the drug concentration under moderate feed rate reductions of 30 kg/h. Furthermore, the continuous blending phases were clearly identified by principal component analysis, moving block of standard deviation, and relative standard deviation, all of them giving consistent results. NIR measurements in a powder stream involved the scanning of powder flowing in a chute. The flow of bulk solids is a complex phenomenon in which powder moves at a certain velocity. The motion of particles produces changes in the density and distribution of the voids. In this study, the velocity of the powder sliding down an inclined chute was measured and used for the estimation of the NIR measured mass. The mass observed during one NIR measurement was estimated to be less than one tablet. Conclusions: This study proved the feasibility of applying NIR spectroscopy for the blend uniformity monitoring of batch and continuous powder mixing. Understanding the critical parameters of powder mixing lead to a robust process and reliable analytical methods. NIR proved to be a valuable and versatile analytical tool in the measurement of bulk solids

Cytochrome c 6-like protein as a putative donor of electrons to photosystem I in the cyanobacterium Nostoc sp. PCC 7119

Most organisms performing oxygenic photosynthesis contain either cytochrome c 6 or plastocyanin, or both, to transfer electrons from cytochrome b 6-f to photosystem I. Even though plastocyanin has superseded cytochrome c 6 along evolution, plants contain a modified cytochrome c 6, the so called cytochrome c 6A, whose function still remains unknown. In this article, we describe a second cytochrome c 6 (the so called cytochrome c 6-like protein), which is found in some cyanobacteria but is phylogenetically more related to plant cytochrome c 6A than to cyanobacterial cytochrome c 6. In this article, we conclude that the cytochrome c 6-like protein is a putative electron donor to photosystem I, but does play a role different to that of cytochrome c 6 and plastocyanin as it cannot accept electrons from cytochrome f. The existence of this third electron donor to PSI could explain why some cyanobacteria are able to grow photoautotrophically in the absence of both cytochrome c 6 and plastocyanin. In any way, the Cyt c 6-like protein from Nostoc sp. PCC 7119 would be potentially utilized for the biohydrogen production, using cell-free photosystem I catalytic nanoparticles.Dirección General de Investigación Científica y Técnica BFU2006-01361/BMCJunta de Andalucía PAI BIO022 BIO19

Characterization of TrxC, an Atypical Thioredoxin Exclusively Present in Cyanobacteria

Cyanobacteria form a diverse group of oxygenic photosynthetic prokaryotes considered to be the antecessor of plant chloroplast. They contain four different thioredoxins isoforms, three of them corresponding to m, x and y type present in plant chloroplast, while the fourth one (named TrxC) is exclusively found in cyanobacteria. TrxC has a modified active site (WCGLC) instead of the canonical (WCGPC) present in most thioredoxins. We have purified it and assayed its activity but surprisingly TrxC lacked all the classical activities, such as insulin precipitation or activation of the fructose-1,6-bisphosphatase. Mutants lacking trxC or over-expressing it were generated in the model cyanobacterium Synechocystis sp. PCC 6803 and their phenotypes have been analyzed. The ΔtrxC mutant grew at similar rates to WT in all conditions tested although it showed an increased carotenoid content especially under low carbon conditions. Overexpression strains showed reduced growth under the same conditions and accumulated lower amounts of carotenoids. They also showed lower oxygen evolution rates at high light but higher Fv’/Fm’ and Non-photochemical-quenching (NPQ) in dark adapted cells, suggesting a more oxidized plastoquinone pool. All these data suggest that TrxC might have a role in regulating photosynthetic adaptation to low carbon and/or high light conditions.España, MINECO BIO2016-75634-PJunta de Andalucía P12-BIO-1119 , BIO-28

Chloroplast damage induced by the inhibition of fatty acid synthesis triggers autophagy in chlamydomonas

Fatty acids are synthesized in the stroma of plant and algal chloroplasts by the fatty acid synthase complex. Newly synthesized fatty acids are then used to generate plastidial lipids that are essential for chloroplast structure and function. Here, we show that inhibition of fatty acid synthesis in the model alga Chlamydomonas reinhardtii activates autophagy, a highly conserved catabolic process by which cells degrade intracellular material under adverse conditions to maintain cell homeostasis. Treatment of Chlamydomonas cells with cerulenin, a specific fatty acid synthase inhibitor, stimulated lipidation of the autophagosome protein ATG8 and enhanced autophagic flux. We found that inhibition of fatty acid synthesis decreased monogalactosyldiacylglycerol abundance, increased lutein content, down-regulated photosynthesis, and increased the production of reactive oxygen species. Electron microscopy revealed a high degree of thylakoid membrane stacking in cerulenin-treated cells. Moreover, global transcriptomic analysis of these cells showed an up-regulation of genes encoding chloroplast proteins involved in protein folding and oxidative stress and the induction of major catabolic processes, including autophagy and proteasome pathways. Thus, our results uncovered a link between lipid metabolism, chloroplast integrity, and autophagy through a mechanism that involves the activation of a chloroplast quality control system.Ministerio de Economía y Competitividad BFU2015-68216-PJunta de Andalucía CVI-7336, BIO2015-74432-JI

Cerámica y sociedad : problemas metodológicos en el estudio de la cerámica

Jornadas de Jóvenes en Investigación Arqueológica, JIA (3as : 5-7 de mayo 2010 : Universitat Autònoma de Barcelona). Sesión 8. El producto cerámicoEn este artículo reflexionamos sobre los problemas que nos encontramos al estudiar la cerámica. Siendo uno de los elemento más valiosos a la hora de documentarnos sobre una sociedad, no podemos quedarnos sólo en el objeto, sino que debemos comprender qué nos aporta. Dados los diferentes enfoques existentes para el estudio de los materiales cerámicos, desde aquí, analizamos el método de trabajo utilizado en su valoración, a partir de las limitaciones propias del material y de la metodología. Presentamos cuales son las barreras que nos encontramos al estudiar la cerámica antigua, aspectos como el origen y difusión de las pastas, o la función y el uso de los recipientes nos siguen resultando complicadas o contradictorias en la comprensión de la cerámica. Al mismo tiempo otros elementos de estudio tales como la determinación de la coloración o la orientación de la pieza, nos plantean dificultades metodológicas.In this paper we reflect on the problems that we have studying ceramics. As one of the most valuable items to research a society, we cannot remain only on the object, we must understand what it means. There are different approaches to study ceramic materials, here, we analyse the methodology used, according to the limitations of the material and the techniques. We show which are the troubles when we are studying the ancient pottery, aspects such as the origin and diffusion of pastas, or the functionality and use of containers are complicated or contradictory to us. At the same time other elements of study as determining the colour or the orientation of the piece, raise us methodological difficulties.En aquest article reflexionem sobre els problemes que ens trobem en l'estudi de la ceràmica. Essent un dels elements més valuosos a l'hora de documentar-nos d'una societat, no podem quedar-nos tan sols en l'objecte, ans hem de comprendre què ens aporta. Donats els diferents enfocaments existents per l'estudi dels materials ceràmics, des d'aquí, analitzem el mètode de treball utilitzant en la seva valoració, a partir de les limitacions pròpies del material i la metodologia. Presentem quines son les barreres que ens trobem en l'estudi de la ceràmica antiga, aspectes com l'origen i difusió de les pastes, o la funció i ús dels recipients ens segueixen resultant complicades o contradictòries en la comprensió de la ceràmica. Al mateix temps altres elements d'estudi tals com la determinació de la coloració o la orientació de la peça, ens plantegen dificultats metodològiques

Evidencia de la didáctica como resultado de un programa de formación docente en psicomotricidad fina

This article is the result of the convergence of three scientific visions, didactics, teacher training, and psychomotricity after analyzing the outcomes of the Participatory Action Research (PAR) carried out in the state of Carabobo-Venezuela, by using a sample formed by 12 teachers who designed 16 fine psychomotricity activities for various levels of early childhood education after being trained on this particular area. The design of these activities includes cognitive, sensory, and motor aspects, as well as the usage of stimulating and sensitive materials. Also, it attends children’s needs taking into consideration the syllabus and projects of each classroom. Teacher training not only provides learning to the teacher but also provides a sense of reflection and empathy with the global processes that favor the integral development of children being the didactic of training the trainers fundamental axis to be transmitted and evidenced in the present work. The 16 activities were validated through the expert judgment technique. The experts specialized in the early childhood education field have different performance profiles and years of experience. The reliability of expert judgment was determined by the degree of agreement between them applying the Kendall rank correlation coefficient.Este artículo es el resultado de la convergencia de tres visiones científicas, didáctica, formación docente y psicomotricidad tras analizar los resultados de una Investigación Acción Participativa (IAP) realizada en el estado Carabobo- Venezuela, a través de una muestra de 12 docentes. Se diseñaron 16 actividades de psicomotricidad fina para varios niveles de educación infantil después de recibir capacitación en esta área, en particular. El diseño de estas actividades incluye aspectos cognitivos, sensoriales y motores, así como el uso de materiales estimulantes y sensibles. Además, atiende las necesidades de los niños teniendo en cuenta el programa y los proyectos de cada aula. La formación docente no solo brinda aprendizajes al docente sino que también brinda un sentido de reflexión y empatía con los procesos globales que favorecen el desarrollo integral de los niños, siendo la didáctica de la formación de los docentes un eje fundamental a transmitir y evidenciar en el presente trabajo. Las 16 actividades fueron validadas mediante la técnica de juicio de expertos. Los expertos especializados en el campo de la educación infantil tienen diferentes perfiles de desempeño y años de experiencia. La confiabilidad del juicio de expertos se determinó por el grado de acuerdo entre ellos, aplicando el coeficiente de correlación de rango de Kendall

La comunicación en las instituciones de carácter público: de lo institucional a lo participativo

La teoría de la comunicación, como explicación argumentada de todarelación comunicativa, se convierte en la fundamentación del quehacer dela comunicación organizacional. El siguiente es un artículo de reflexión, quetrabaja una perspectiva hermenéutica de los conflictos comunicativos delHospital Eduardo Arredondo Daza de la ciudad de Valledupar, los cualesobligan a un análisis teórico desde una mirada explicativa e interpretativa. Loinstitucional no excluye lo participativo, en tanto es la participación el factorclave a través del cual se logran procesos de empoderamiento de los diversosactores, siendo la participación la vía socio-humanística de corte cualitativomás coherente, para la adaptación de escenario y ambientes dialógicossocialmente compartidos

Development of an Emergency Radio Beacon for Small Unmanned Aerial Vehicles

Emergency locator transmitters (ELTs) used to locate manned aircrafts are not well suited to find and recover small crashed unmanned aerial vehicles (UAVs). ELTs utilize an international satellite system for search and rescue (Cospas-Sarsat System), which should leverage its expensive resources to save lives as a priority. Besides, ELTs are too big and heavy to be used within small UAVs. Some of the existing solutions for this problem are based on receivers that detect signal strength, which may be a long and tedious process not suitable for user needs. Others do not have enough range or require radio license and expensive amateur radio receivers. This paper presents an emergency radio beacon specifically designed to locate small UAVs. It is triggered automatically in the event of a crash and allows finding and recovering a crashed UAV in a fast and simple way. It meets not only the required specifications of user-friendliness, size and weight of this kind of application, but also it is a high precision and low cost device. Besides, it has enough range and endurance. The experiments carried out show the operation of the proposed system

Diversity of N2-fixing cyanobacteria from Andalusian paddy fields and analysis of their potential as bioinoculants

The marshes of the Guadalquivir River contain the largest area of rice cultivation in Spain, where more than 40,000 ha are used every year for rice production. These wetland areas provide a perfect place for rice cultivation, and represent a unique aquaticterrestrial habitat that hold more wintering waterfowl than any other European wetland. Paddies require large amounts nitrogen and phosphorus for their growth, development and production. Though, flooded conditions used for rice cultivation drastically diminish efficiency inorganic nitrogen fertilizers, being only 30–40% used by the plant, and in some cases even less. Large amounts of nitrogen fertilizers are dissolved in the surface water and lost, causing environmental pollution and health problems due to losses through N2O and NO volatilization, denitrification, and leaching (Ishii et al., 2011)

Action Guide for the Community Pharmacist in Inflammatory Bowel Disease

Introducción: La presente guía está enfocada en ayudar al paciente con Enfermedad Inflamatoria Intestinal que asiste a la oficina de farmacia, mediante la oferta de servicios de atención farmacéutica como son la farmacovigilancia y el seguimiento farmacoterapéutico que buscan promover la inclusión del farmacéutico comunitario en el equipo de salud. Objetivo: Elaborar una guía de actuación para el Farmacéutico Comunitario en pacientes con Enfermedad Inflamatoria Intestinal Metodología: El protocolo de revisión sistemática para la elaboración de la presente guía fue desarrollado en base a los criterios en el que se establecen: Identificar la pregunta de investigación, realizar un plan de estrategia en bases de datos electrónicos, utilizar un enfoque de equipo para la extracción de información, realizar un análisis temático y resumir la información. Resultados: La elaboración de algoritmos en la presente guía permite aportar información oportuna para el farmacéutico comunitario acorde a las características individuales que se presenten en cada paciente permitiendo detectar de manera rápida y eficaz los problemas que se pudieren presentar durante la enfermedad para poder prevenirlos e intervenir de manera oportuna. Discusión: La información aportada ayuda a reforzar los conocimientos teórico-prácticos del farmacéutico comunitario, incentivándolo a promover y promocionar servicios de atención farmacéutica enfocados en las necesidades del pacienteIntroduction: This guide is focused on helping the patient with Inflammatory Bowel Disease who attends the pharmacy office by offering pharmaceutical care services such as pharmacovigilance and pharmacotherapeutic follow-up that seek to promote the inclusion of the community pharmacist in the team of health. Objective: To develop an action guide for the Community Pharmacist in patients with Inflammatory Bowel Disease Methodology: The systematic review protocol for the development of this guide was developed based on the criteria in which they establish: Identify the research question, make a strategy plan in electronic databases, use a team approach to the extraction of information, perform a thematic analysis and summarize the information. Results: The development of algorithms in this guide allows to provide timely information for the community pharmacist according to the individual characteristics presented in each patient, allowing the rapid and effective detection of problems that may arise during the illness in order to prevent and intervene timely. Arguement: The information provided helps to strengthen the theoretical and practical knowledge of the community pharmacist, encouraging him to promote and promote pharmaceutical care services focused on the needs of the patien