No Brasil a esquistossomose é causada pela espécie Schistosoma mansoni e leva principalmente à formação de granulomas e fibroses, hipertensão portal e hepatoesplenomegalia. O praziquantel (PZQ) é o fármaco de primeira escolha para o tratamento e possui baixa solubilidade aquosa, sendo necessárias altas doses para ação terapêutica. A taxa de dissolução do PZQ é fator limitante para a sua biodisponibilidade, portanto, melhorar sua solubilidade é fundamental. O objetivo deste trabalho foi aumentar a solubilidade do PZQ pela obtenção de grânulos contendo dispersões sólidas deste fármaco pelo processo hot melt em leito fluidizado. Além disto, buscou-se estudar a fluidodinâmica e as variáveis do processo de granulação. Inicialmente, dispersões sólidas foram preparadas por simples fusão em polietilenoglicol (PEG) 4000 e PEG 6000 nas proporções 2:1; 1:1; 1:2; 1:5 e 1:10 e estas foram caracterizadas por teste de solubilidade, difração de raios-X, espectroscopia em infravermelho e análises térmicas (DSC e TG). Foram obtidas dispersões sólidas com uma solubilidade duas vezes maior do PZQ, uma menor cristalinidade, uma possível interação fármaco-carreador e sem degradação ou alteração nos principais grupos funcionais. Com estes resultados, a dispersão sólida 1:10 PZQ:PEG 6000 foi escolhida para a etapa da granulação. Os granulados foram obtidos utilizando o planejamento fatorial Box Behnken com as seguintes variáveis: % de dispersão sólida, proporção PZQ:PEG das dispersões e carga de lactose spray-dried (SD) (g). A caracterização dos grânulos foi realizada pelos testes: granulometria, densidade aparente, densidade compactada, fator de Hausner, índice de Carr, ângulo de repouso e doseamento do fármaco, sendo todas estas propriedades avaliadas pela técnica de superfície de resposta (ANOVA). A análise estatística demonstrou que as características dos granulados são, na maioria dos casos, dependentes da % de dispersão sólida e da proporção de PZQ:PEG, sendo satisfatórios e toleráveis os resultados do fluxo dos granulados. Os três melhores granulados foram escolhidos para as análises de microscopia eletrônica de varredura, espectroscopia em infravermelho, difração de raios-X, análise térmica e perfil de dissolução. Estas análises mostraram que nos grânulos houve diminuição da cristalinidade, possíveis interações entre PZQ, PEG e lactose, além do grande aumento no perfil de dissolução. Com estes resultados, confirmam-se as vantagens da granulação por hot melt em leito fluidizado e a importância do estudo de suas variáveis. / In Brazil, schistossomiasis is mainly attributed to the species Schistosoma mansoni, which causes granulomas and fibrosis, portal hypertension and hepatosplenomegaly. Praziquantel (PZQ) is the first choice in the treatment; however, it has low water solubility, thus requiring high doses for a proper therapeutical result. The PZQ dissolution rate is the limiting factor for its bioavailability; therefore, it is fundamental to improve of this drug solubility. The objective of this work was to increase the PZQ solubility with the production of granules containing its solid dispersions, prepared by hot melt process in fluidized bed. Moreover, the fluid dynamic and several variables of the process were studied. First, solid dispersions were prepared by mixing with melted polyethylene glycol (PEG) 4000 and PEG 6000 at the ratios of 2:1; 1:1; 1:2; 1:5 and 1:10. These were characterized by solubility test, x-ray powder diffraction, fourier transform infrared spectroscopy and thermal analyses (DSC and TG). Solid dispersions were obtained with PZQ solubility two times higher than the pure drug, lower crystallinity and without degradation or alteration in the main functional groups. With these results, the solid dispersion 1:10 PZQ:PEG 6000 was chosen for the studies of granulation. The granulates were obtained using the Box Behnken factorial design with the following independent variables: % of solid dispersion, ratio PZQ:PEG in the dispersions and amount of spray-dried lactose (g). The granules characterization was made by the tests of granulometry, bulk density, tapped density, Hausner ratio, Carr index, angle of repose and PZQ assay. In addition, all these properties were evaluated by response surface technique (ANOVA). The statistical analysis, in most cases, showed that the granules characteristics depend significantly on the % of solid dispersion and on the ratio PZQ:PEG. The results on the granules flow properties are satisfactory and acceptable for tableting. The three granulates with best properties were submitted to scanning electron microscopy, fourier transform infrared spectroscopy, x-ray powder diffraction, thermal analysis and dissolution test. These analyses showed that there were, in the granules, decrease of crystallinity, possible interaction among PZQ, PEG and lactose, and also, greater increase in the dissolution test. The advantages of fluid bed hot melt granulation and the importance of studying the process variables are confirmed by the results in this work.

Bibliography: 208-218.

As part of the production of certain solid-dosage pharmaceuticals, granulated ingredients are dried in a batch fluidized bed dryer. Currently, the determination of the completion of the drying process is accomplished through measurements of product or outlet air temperatures. No quantitative measurement of hydrodynamic behaviour is employed. Changes in bed hydrodynamics caused by variations in fluidization velocity may lead to increased particle attrition. In addition, excessive desiccation of the granules caused by inaccurate determination of the drying endpoint may lead to an increase in the thermal and mechanical stresses within the granules. The activity of future high-potency or peptide based drug products may be influenced by these effects. Therefore, the quantification of hydrodynamic changes may be a key factor in the tighter control of both fluidization velocity and product moisture, which are critical for maintaining product quality. <p>High-frequency measurements of pressure fluctuations in a batch fluidized bed dryer containing pharmaceutical granulate have been used to provide a global, non-intrusive indication of the hydrodynamic changes occurring throughout the drying process. A chaotic attractor comparison statistical test known as the S-statistic, has been applied to quantify these changes in drying and a related unit operation, fluidized bed granulation. The S-statistic showed a sensitivity to moisture which is not seen with frequency and amplitude analysis. In addition, the S-statistic has been shown to be useful in identifying an undesirable bed state associated with the onset of entrainment in a bed instrumented for the collection of both pressure fluctuation and entrainment data. Thus, the use of the S-statistic analysis of pressure fluctuations may be utilized as a low-cost method for determining product moisture or changes hydrodynamic state during fluidized bed drying. <p>Electrical capacitance tomography (ECT) has also been applied in this study to image the flow structure within a batch fluidized bed used for the drying of pharmaceutical granulate. This represents the first time that ECT has been applied to a bed of wet granulate material. This was accomplished through the use of a novel dynamic correction technique which accounts for the significant reduction in electrical permittivity occurring as moisture is lost during the drying process. The correction has been independently verified using x-ray tomography. <p>Investigation of the ECT images taken in the drying bed indicates centralized bubbling behaviour for approximately the first 5 minutes of drying. This behaviour is a result of the high liquid loading of the particles at high moisture. Between moisture contents of 18-wt% and 10-wt%, the tomograms show an annular pattern of bubbling behaviour with a gradual decrease in the cross-sectional area involved in bubbling behaviour. The dynamic analysis of this voidage data with the S-statistic showed that a statistically significant change occurs during this period near the walls of the vessel, while the centre exhibits less variation in dynamic behaviour. The changes identified by the S-statistic analysis of voidage fluctuations near the wall were similar to those seen in the pressure fluctuation measurements. This indicates that the source of the changes identified by both these measurement techniques is a result of the reduction in the fraction of the bed cross-section involved in bubbling behaviour. At bed moisture contents below 5-wt%, rapid divergence was seen in the S-statistic applied to both ECT and pressure fluctuation measurements. This indicates that a rapid change in dynamics occurs near the end of the drying process. This is possibly caused by the entrainment of fines at this time, or the build-up of electrostatic charge. <p>The use of the complimentary pressure fluctuation and ECT measurement techniques have identified changes occurring as a result of the reduction of moisture during the drying process. Both the localized changes in the voidage fluctuations provided by the ECT imaging and the global changes shown by the pressure fluctuation measurements indicate significant changes in the dynamic behaviour caused by the reduction of moisture during the drying process. These measurement techniques could be utilized to provide an on-line indication of changes in hydrodynamic regime. This information may be invaluable for the future optimization of the batch drying process and accurate determination of the drying endpoint.

As part of the production of certain solid-dosage pharmaceuticals, granulated ingredients are dried in a batch fluidized bed dryer. Currently, the determination of the completion of the drying process is accomplished through measurements of product or outlet air temperatures. No quantitative measurement of hydrodynamic behaviour is employed. Changes in bed hydrodynamics caused by variations in fluidization velocity may lead to increased particle attrition. In addition, excessive desiccation of the granules caused by inaccurate determination of the drying endpoint may lead to an increase in the thermal and mechanical stresses within the granules. The activity of future high-potency or peptide based drug products may be influenced by these effects. Therefore, the quantification of hydrodynamic changes may be a key factor in the tighter control of both fluidization velocity and product moisture, which are critical for maintaining product quality. <p>High-frequency measurements of pressure fluctuations in a batch fluidized bed dryer containing pharmaceutical granulate have been used to provide a global, non-intrusive indication of the hydrodynamic changes occurring throughout the drying process. A chaotic attractor comparison statistical test known as the S-statistic, has been applied to quantify these changes in drying and a related unit operation, fluidized bed granulation. The S-statistic showed a sensitivity to moisture which is not seen with frequency and amplitude analysis. In addition, the S-statistic has been shown to be useful in identifying an undesirable bed state associated with the onset of entrainment in a bed instrumented for the collection of both pressure fluctuation and entrainment data. Thus, the use of the S-statistic analysis of pressure fluctuations may be utilized as a low-cost method for determining product moisture or changes hydrodynamic state during fluidized bed drying. <p>Electrical capacitance tomography (ECT) has also been applied in this study to image the flow structure within a batch fluidized bed used for the drying of pharmaceutical granulate. This represents the first time that ECT has been applied to a bed of wet granulate material. This was accomplished through the use of a novel dynamic correction technique which accounts for the significant reduction in electrical permittivity occurring as moisture is lost during the drying process. The correction has been independently verified using x-ray tomography. <p>Investigation of the ECT images taken in the drying bed indicates centralized bubbling behaviour for approximately the first 5 minutes of drying. This behaviour is a result of the high liquid loading of the particles at high moisture. Between moisture contents of 18-wt% and 10-wt%, the tomograms show an annular pattern of bubbling behaviour with a gradual decrease in the cross-sectional area involved in bubbling behaviour. The dynamic analysis of this voidage data with the S-statistic showed that a statistically significant change occurs during this period near the walls of the vessel, while the centre exhibits less variation in dynamic behaviour. The changes identified by the S-statistic analysis of voidage fluctuations near the wall were similar to those seen in the pressure fluctuation measurements. This indicates that the source of the changes identified by both these measurement techniques is a result of the reduction in the fraction of the bed cross-section involved in bubbling behaviour. At bed moisture contents below 5-wt%, rapid divergence was seen in the S-statistic applied to both ECT and pressure fluctuation measurements. This indicates that a rapid change in dynamics occurs near the end of the drying process. This is possibly caused by the entrainment of fines at this time, or the build-up of electrostatic charge. <p>The use of the complimentary pressure fluctuation and ECT measurement techniques have identified changes occurring as a result of the reduction of moisture during the drying process. Both the localized changes in the voidage fluctuations provided by the ECT imaging and the global changes shown by the pressure fluctuation measurements indicate significant changes in the dynamic behaviour caused by the reduction of moisture during the drying process. These measurement techniques could be utilized to provide an on-line indication of changes in hydrodynamic regime. This information may be invaluable for the future optimization of the batch drying process and accurate determination of the drying endpoint.

Simultaneous solution of the conservation equations for energy and chemical species in conjunction with radiative transfer equation was carried out by coupling a previously developed and tested system model of fluidized bed combustion (FBC) to an existing radiation model. The predictive accuracy of the coupled code was assessed by applying it to 0.3 MWt METU Atmospheric Bubbling Fluidized Bed Combustor (ABFBC) Test Rig burning lignite in its own ash and comparing its predictions with the measured temperatures and concentrations of gaseous species along the combustor and radiative heat fluxes incident on the refractory-lined freeboard walls on two combustion tests, with and without recycle. The predictions of the coupled code were found to be in good agreement with the measurements. For the investigation of the significance of coupling of the radiation model to the system model, temperature predictions of the coupled code were compared with those obtained by the original system model. It was found that the effect of incorporating a radiation model into the system model on the predictions was not significant because the high temperatures of refractory-lined freeboard walls and high surface to volume ratio of the test rig under consideration cause the incident radiative heat fluxes to be dominated by walls rather than the particle laden gas emissions. However, in industrial boilers, freeboard is surrounded by water-cooled membrane walls and boilers have much lower surface to volume ratio. In order to examine the effects of both on radiation in industrial boilers, an investigation was carried out on 16 MWt Stationary Fluidized Bed Boiler (SFBB) by applying radiation model, in isolation from the system model, to the freeboard of the boiler. It was found that in the boiler, incident radiative heat fluxes were dominated by particle laden gas emissions. In brief, the coupled code proposed in this study proves to be a useful tool in qualitatively and quantitatively simulating the processes taking place in an atmospheric fluidized bed boilers.

The purpose of this project was to produce a “greener” cement from granulated ground blast furnace slag (GGBS) using non-Portland cement activation. By eventually developing “greener” cement, the ultimate goal of this research project would be to reduce the amount of Portland cement used in concrete, therefore reducing the amount of carbon dioxide emitted into the atmosphere during cement production. This research studies the behavior of mineral binders that do not contain Portland cement but instead comprise GGBS activated by calcium compounds or fluidized bed combustion (FBC) bottom ash. The information described in this paper was collected from experiments including calorimetry, which is a measure of the release of heat from a particular reaction, the determination of activation energy of cement hydration, mechanical strength determination, and pH measurement and identification of crystalline phases using X-ray diffraction (XRD). The results indicated that it is possible to produce alkali-activated binders with incorporated slag, and bottom ash, which have mechanical properties similar to ordinary Portland cement (OPC). It was determined that the binder systems can incorporate up to 40% bottom ash without any major influence on binder quality. These are positive results in the search for “greener cement”.

Selective oxidation and sulfation roasting of nickel concentrate followed by leaching was investigated as a novel route for nickel production. In the oxidation roasting stage, the iron species in the nickel concentrate was preferentially oxidized to form iron oxides, leaving non-ferrous metals (Ni, Cu, Co) as sulfides. The roasted product was then sulfation roasted to convert the sulfides of the latter metals into water-soluble sulfates. The sulfates were then leached into solution for further recovery and separation from iron oxides. The oxidation of nickel concentrate was firstly studied by means of thermogravimetric and differential thermal analysis over a wide temperature range. A reaction scheme was deduced, in which preferential oxidation of iron sulfide species occurred over a wide temperature range up to about 700 ºC, forming a Ni1-xS core with iron oxide shell. A batch fluidized bed roaster was then constructed to study the oxidation and sulfation roasting of nickel sulfide concentrate. Oxidation roasting tests were carried out at temperatures between 650 °C and 775 °C. It was found that low temperatures (e.g. 650 °C) are favorable for the preferential oxidation of iron sulfide species while minimizing the formation of nickeliferous oxides, i.e. trevorite and NiO. Several parameters were varied in the sulfation roasting experiments, including the sulfation gas flowrate, sulfation roasting temperature, the addition of Na2SO4, sulfation roasting time, and the oxidation roasting temperature. Under optimized conditions of sulfation gas composition (95% air, 5% SO2), temperature (700 °C), Na2SO4 addition (10 wt%) and time (150 min), the conversions to sulfates were 79% Ni, 91% Cu, and 91% Co. Only 5% Fe forms water-soluble sulfate. The residue from the leaching of calcine in water contained 49% Fe and 10% Ni, which is a suitable feedstock for the production of ferronickel alloys. Therefore, further studies were also conducted to evaluate the reduction behavior of the residue with CO, H2 and graphite.

A systematic in-depth study has been undertaken to establish the corrosion mechanism of a Model 25Cr-35Ni-Fe alloy and four commercial alloys HP40Nb, AISI314, HP40Al and Alloy 800H in low oxygen, high sulphur and carbon containing environments typically found in coal gasification and fluidised bed combustion processes. A review of present knowledge of corrosion processes in purely oxidizing, sulphidizing and carburizing environments and multiple reactant carburizing/ oxidizing, carburizing/sulphizing and oxidizing/sulphidizing environments is given. The experimental programme was designed to establish the role of sulphur on the corrosion process by studying corrosion mechanisms in a sulphurfree H2-7%C0-1.5%H2o gas, a low sulphur H2-7%C0-1.5%H20-0.2%H 2 S gas (pS2_8= 10 bar), and a high sulphur H 2 -7%C0-1.5%H 2 0-0.6%H 2 S gas (pS = lO bar) at 800'C. All_21j_hree environments had a constant partiaf pressure of oxygen (po2 = 10 bar) and carbon activity (ac = 0.3). In the sulphur-free gas the Model alloy formed a thin uniform cr 2 o 3 layer which grew at a constant parabolic rate throughout the exposure period of 0 - 5000 hours. Surface working increased the growth rate and thickness of the Cr 2 o 3 layer but created a large number of cracks and pores which allowed carbon containing gaseous species to diffuse through the oxide to form carbide precipitates in the alloy substrata. Alloying additions of Si promoted the formation of an inner SiO layer which reduced the corrosion rate by cutting off the outward diffusion of Cr, Mn and Fe. Alloying additions of Mn promoted the formation of an additional outer (Mn, Fe )Cr 2o 4 layer. The 3. 5% Al content of the HP40Al was insufficient to form a complete Al 2 o3 layer. Alloy 800H was susceptible to localised internal oxidation. Adding a low level of sulphur (0.2% H 2 S) to the gas increased the corrosion rate of the Model alloy in the 1nitial stages. This rate gradually slowed down before becoming parabolic after 1000 - 2000 hours. This was due to the nucleation of sulphides in addition to oxides. The oxides and sulphides grew side by side until the oxides overgrew the sulphides to form a complete Cr 2o3 layer which cut off further ingress of sulphur from the gas. The entrapped sulphides promoted localized thickening of the oxide layer. Eventually the sulphur redistributed from the sulphides in the scale to internal sulphide precipitates in the alloy with the corrosion rate returning to that of the sulphur-fre,e gas for the rest of the exposure period (5000 hours total). In the commercial alloys the internal sulphide precipitates prevented the inner Si02 layer becoming complete. Sulphur doped the (Mn, Fe) Cr 2 0 4 outer layer ana the intermediate Cr 2o3 layer formed from the spinal layer, increasing the number of cation . vacancies and the growth rate of the scale. These factors caused a massive Cr depletion of the alloy substrata after several thousand hours. The internal carbides became unstable which led to a massive amount of internal attack and a dramatic increase (breakaway) in the corrosion rate. Due to its thickness and the presence of Si02 inner layer the external scale became susceptible to spallation. If this occurred the oxides and sulphides nucleated on the alloy surface again but sulphides. protective alloy. insufficient Cr was available for the oxides to overgrow the The sulphides therefore grew to form a fast growing nonsulphide scale which soon led to catastrophic failure of the Increasing the level of sulphur in the gas to 0.6% H2S caused oxides and sulphides to nucleate on the surface, but in this case the sulphides overgrew the oxides to form thick fast growing non-protective sulphide scales on all the alloys.

Resumo: O reator aeróbio de leito fluidizado com circulação interna emprega microorganismos aderidos a um meio suporte uniforme (areia), removendo tanto matéria orgânica quanto nitrogenada. Neste experimento foram estudados dois reatores com 2,6 m de altura cuja diferença era o diâmetro do tubo interno (125 e 150 mm) e foram aplicadas diferentes concentrações de meio suporte ao longo do estudo (100, 125 e 150 g.L-1). Ensaios realizados com água limpa utilizando traçador (NaCl) e sondas de condutividade elétrica mostraram que, nas vazões de ar entre 1500 - 3000 L.h-1, ocorre circulação suficiente para a suspensão do meio suporte. O esgoto doméstico passou por peneiramento estático e foram realizadas análises de DBO, DQO, NT, Namon, NO2, NO3, sólidos, espessura do biofilme, turbidez, temperatura, pH, OD e testes microbiológicos (Gram, esporos e catalase). Observou-se que a adição de meio suporte influencia positivamente na eficiência de remoção de matéria nitrogenada, e que uma menor diferença entre as áreas interna e externa facilitam o equilíbrio do sistema, apresentando assim, eficiências melhores. / Abstract: Aerobic fluidized bed reactor with internal-loop uses microorganisms attached to a uniform carrier (sand), removing carbonaceous and nitrogenous matter. In this experimental work two reactors with 2,6 m height were studied. The main difference between both reactors was the inner tube diameter (125 and 150mm). Different carrier concentrations were applied in that study (100, 125 and 150g.L-1). Experiments with clean water using a marker (NaCl) and electrical conductivity probes showed that with flow taxes between 1500 - 3000 L.h-1 occurs sufficient circulation to suspend the carrier. The sewage passed by static screening and analyses of BOD, COD, total nitrogen, Namon, NO2, NO3, suspend solids, biofilm thickness, turbidity, temperature, pH, dissolved oxygen and microbiological test (Gram, spores and catalysis) were realized. In that work, was observed that the addition of carrier has positive influences on nitrogenous matter removal efficiency, and lower differences between indoor/outdoor area facilitate system balance, showing better efficiencies. / Orientador: Milton Dall'Aglio Sobrinho / Coorientador: Dib Gebara / Banca: Vanildo Luiz Del Bianchi / Banca: Ranulfo Monte Alegre / Mestre

Submitted by Emanuel Varela Cardoso (emanuel.varela@ufcg.edu.br) on 2018-08-17T19:08:47Z No. of bitstreams: 1 DANIELLE DE LIMA VIEIRA – DISSERTAÇÃO (PPGEM) 2017.pdf: 2977283 bytes, checksum: 76868ac7a0711cd9560eee5a78b8bf43 (MD5) / Made available in DSpace on 2018-08-17T19:08:47Z (GMT). No. of bitstreams: 1 DANIELLE DE LIMA VIEIRA – DISSERTAÇÃO (PPGEM) 2017.pdf: 2977283 bytes, checksum: 76868ac7a0711cd9560eee5a78b8bf43 (MD5) Previous issue date: 2017-09 / Na indústria petroquímica e de processamento de petróleo o riser é o principal equipamento da unidade de craqueamento catalítico fluido (FCC), utilizado para o refino de frações pesadas do petróleo. Para o projeto e otimização do riser é essencial compreender a termofluidodinâmica da mistura gás -sólido no seu interior. Neste aspecto a fluidodinâmica computacional (CFD) tem demonstrado ser uma boa alternativa para o estudo de sistemas complexos. Portanto, este trabalho tem como objetivo estudar a termofluidodinâmica de um riser de FCC com alto fluxo, via CFD usando o software comercial Ansys Fluent versão 15. O modelo matemático é baseado na abordagem Euleriana – Euleriana, considerando a Teoria Cinética do Escoamento Granular (KTGF) e o modelo de turbulência de duas equações k - ϵ Disperso. Resultados numéricos dos campos de velocidade, fração volumétrica e pressão das fases gasosa e particulada, a temperatura constante, são apresentados, analisados e comparados com dados de uma planta experimental com 76 mm ID e altura de 10 m, apresentando boa concordância, exceto nas regiões com alta densidade de partículas. Assim, o modelo proposto mostrou-se mais adequado a representação do fluxo em regiões e condições operacionais que resultam em menores concentrações de partículas (menor fluxo de sólidos e/ou maior vazão do gás). / In the petrochemical and oil processing industry riser is the main equipment of the fluid catalytic cracking (FCC) unit, used for the refining of heavy petroleum fractions. For design and optimization of riser, it is essential to understand the thermo fluid dynamics of the gas-solid mixture inside. In this respect, computational fluid dynamics (CFD) has been shown to be a good alternative for the study of complex systems. Therefore, this work aims to study the thermo fluid dynamics of a FCC riser with high flux, via CFD using commercial software Ansys Fluent version 15. The mathematical model is based on the Eulerian - Eulerian approach, considering a Kinetic Theory of Granular Flow (KTGF) and the k - ϵ two equations turbulence model. Numerical results of fields of velocity, volumetric fraction and pressure of the gas and particulate phases, at constant temperature, are presented, analyzed and compared with data of an experimental plant with 76 mm ID and 10 m height, presenting good agreement, except in regions with high particle density. Thus, the proposed model showed better representation of the flow in regions and operating conditions that result in lower particle concentrations (lower solids flow and / or higher gas flow).