The fluid bed granulation is a well-established method how to improve such properties of powders as flowability and increase content uniformity of the tablets. In this thesis, there was evaluated a granulation process on a lab scale fluid Glatt bed granulator and optimized for highest possible yield. Product yield in the size range of 80-90 % of granules and process reproducibility were stated as most effective. The product was analysed for its particle size distribution, the API distribution within the different particle size fractions and the flowability of the final granules. For process optimization, the most critical parameters such as spraying rate, particle size of raw materials and fluid bed pressure were identified and evaluated. As the highest-yielding dosage for the powder binder was found the spraying rate of 9 g/min. Changes in bed fluid pressure and nozzle pressure showed no significant improvement. Different grades of caffeine were compared for their impact on the granulation properties. Sieved caffeine enhanced yield of the product and reproducibility compared to bulk or disagglomerated caffeine.

Orientadores: Florencia Cecilia Menegali, Gustavo Cesar Dacanal / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-17T15:47:50Z (GMT). No. of bitstreams: 1 Hirata_TalitaAkemiMedeiros_M.pdf: 4514869 bytes, checksum: b65281144cb361473556f15e38d9a709 (MD5) Previous issue date: 2011 / Resumo: Com o aumento da variedade de produtos em pó, produzidos por diversas indústrias alimentícias, há a necessidade de informações detalhadas a respeito do seu manuseio e processamento voltadas para a aplicação em diversos produtos alimentares. O aumento do tamanho de partículas finas pelo processo de aglomeração em leito fluidizado proporciona benefícios que incluem redução de perdas de finos e perigo ou desconforto na manipulação, e principalmente, melhoria das propriedades de instantaneização do pó, por exemplo, solubilidade, dispersão em líquidos etc. Os leitos fluidizados pulsados possuem uma série de vantagens em relação aos leitos convencionais, podendo-se destacar a fácil fluidização de partículas irregulares com tamanhos distintos. A pectina é muito conhecida como agente geleificante e vem sendo utilizada na forma de pó. Este trabalho teve como objetivo estudar as modificações nas propriedades físicas da pectina em pó produzida por aglomeração em leito fluidizado pulsado. As condições ótimas de processo foram obtidas por meio de planejamento experimental, ou delineamento composto central 24. As variáveis estudadas foram temperatura do ar, vazão de ligante, velocidade de fluidização do ar e frequência de pulsação do ar. Obteve-se um rendimento no processo superior a 80% e o aumento de tamanho da partícula foi de quase 340%. O produto foi caracterizado por análises de umidade, instantaneização, dissolução, morfologia, distribuição do tamanho da partícula e do diâmetro médio, fluidez e fragilidade do aglomerado. O aglomerado se mostrou mais poroso e irregular comparado com a matéria-prima que é mais compacta e circular. As partículas aglomeradas apresentaram melhora na aparência, na fluidez, bem como nas propriedades de instantaneização e dissolução. Verificou-se também que a tensão na ruptura e o módulo de elasticidade do gel formado pelo produto aglomerado foram superiores ao gel da matéria-prima / Abstract: The agglomeration of food powders is commonly used to produce porous granules with higher wettability and dispersability. The agglomeration process promotes the particles enlargement and reduction of fines and result in some benefits, including lower rates of particles elutriation and danger reduction in handling or inhalation. Fluid bed agglomeration is commonly used to improve the instant properties of spray-dried food powders. However, the fluidization of spray-dried particles is characterized by cracks and channels. The pulsed fluid bed has some advantages over the conventional fluid bed equipment, including easy fluidization of irregular particles of different sizes. Pectin is widely used in the food industries as a gelling agent and has been used in powder form. The aim of this work was to study the changes in the physical properties of pectin powder produced by agglomeration in pulsed fluidized bed. The optimal process conditions were obtained by a full factorial design 24. The variables studied were fluidizing air temperature, binder flow rate, fluidizing air velocity and air pulsation frequency. Agglomerated process presented a process yield above 80% and an increase of almost 340% in the mean particle diameter. The product was characterized by moisture, wettability, dissolution, morphology, particle size distribution and mean diameter, fluidity and fragility of the agglomerated. The agglomerated was more porous and irregular compared with the raw material that is more compact and circular. The agglomerated particles showed an improvement in appearance, fluidity and the properties of wettability and dissolution. It was also found that the stress at fracture and modulus of elasticity of the gel formed by the agglomerated product were higher than the gel obtained from the raw material / Mestrado / Mestre em Engenharia de Alimentos

The increasing concern for emissions and pollutants from power generation plants has increased the desire for and the study of biomass fuels. Biomass combustion produces less carbon monoxide as well as other greenhouse gases. Black liquor is a byproduct from the Kraft process in making paper. Black liquor can be gasified and used as a fuel in recovery boilers and fluidized bed steam reformers. Recovery boilers have a low efficiency and are used today because of their reliability. Steam reformers have a much higher efficiency but they are a relatively new science and are not as reliable. One of the reasons why steam reformers are not reliable is due to the agglomeration of the particles in the fluidized bed. The particles will stick together, agglomerate, at temperatures much lower than their melting temperature. The strength of these bonds and the temperature at which the bed agglomerates were studied as well as the effect of particle size on the heat transfer coefficient from the heaters to the bed material by means of experimentation and analysis. As the carbon content decreases, the agglomeration temperature also decreases. For 0.3% carbon content coated particles, the agglomeration temperature is approximately 490 ºC. The temperature at which the inter-particle bond strength increases dramatically also decreases. By comparing the inter-particle force with the collision force between particles, it was observed that when the velocity of the particles decreases below 1/500th of the free stream velocity, the particles will agglomerate.

No description available.

The U.S. Food and Drug Administration has accepted the guidelines put forth by the International Conference on Harmonization (ICH-Q8) that allow for operational flexibility within a validated design space. These Quality by Design initiatives have allowed drug manufacturers to incorporate more rigorous scientific controls into their production streams. <br>Fully automated control systems can incorporate information about a process back into the system to adjust process variables to consistently hit product quality targets (feedback control), or monitor variability in raw materials or intermediate products to adjust downstream manufacturing operations (feedforward control). These controls enable increased process understanding, continuous process and product improvement, assurance of product quality, and the possibility of real-time release. Control systems require significant planning and an initial investment, but the improved product quality and manufacturing efficiency provide ample incentive for the expense. <br>The fluid bed granulation and drying unit operation was an excellent case study for control systems implementation because it is a complex unit operation with dynamic powder movement, high energy input, solid-liquid-gas interactions, and difficulty with scale-up development. Traditionally, fluid bed control systems have either used first principle calculations to control the internal process environment or purely empirical methods that incorporate online process measurements with process models. This dissertation was predicated on the development of a novel hybrid control system that combines the two traditional approaches. <br>The hybrid controls reduced the number of input factors for the creation of efficient experimental designs, reduced the variability between batches, enabled control of the drying process for a sensitive active pharmaceutical ingredient, rendered preconditioned air systems unnecessary, and facilitated the collection of data for the development of process models and the rigorous calculation of design spaces. Significant variably in the inlet airstream was able to be mitigated using feedforward controls, while process analytical technology provided immediate feedback about the process for strict control of process inputs. Tolerance surfaces provided the ideal tool for determining design spaces that assured the reduction of manufacturing risk among all future batches, and the information gained using small scale experimentation was leveraged to provide efficient scale-up, making these control systems feasible for consistent use. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences / Pharmaceutics / PhD / Dissertation

Orientador: Florencia Cecilia Menegalli / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-12T23:46:58Z (GMT). No. of bitstreams: 1 Dacanal_GustavoCesar_D.pdf: 5335260 bytes, checksum: a233ac2a96d8752da46e8dfb7a4554c0 (MD5) Previous issue date: 2009 / Resumo: processo de aglomeração de alimentos é muito utilizado quando se deseja aumentar as propriedades de instantaneização de pós obtidos pela secagem em spray dryer. Os produtos obtidos pela secagem em spray são normalmente caracterizados como sendo finos, coesivos e por apresentar difícil fluidização. Deste modo, torna-se conveniente utilizar leitos fluidizados, vibrados ou pulsados, que resultem em um aumento da movimentação das partículas e homogeneidade do leito durante a fluidização, permitindo aglomerar produtos em pó oriundos da secagem em spray dryer. O objetivo deste trabalho foi estudar as mudanças nas propriedades físicas de polpa de acerola e de proteína isolada de soja em pó após o processo de aglomeração em leito fluidizado cônico, e verificar os efeitos do uso de diferentes frequências de pulsação do ar fluidizante durante o processo de aglomeração. A pulsação do ar foi realizada por meio da rotação de uma válvula esfera, instalada abaixo da placa distribuidora de ar. As condições ótimas de processo e os perfis de aumento de tamanho de partículas foram obtidos por meio de planejamentos experimentais e de ensaios de cinéticas de aglomeração. As variáveis de processo estudadas foram o tempo de processo, velocidade e temperatura do ar fluidizante, vazão de líquido ligante, pressão de atomização, altura do bico aspersor e massa de amostra. O produto aglomerado foi caracterizado pelos testes de diâmetro médio e distribuição de tamanho de partículas, tempo de instantaneização, solubilidade, morfologia e conteúdo de umidade. Durante a aglomeração, as partículas da matéria prima coalescem, formando grânulos grossos. A morfologia das partículas também é alterada com o aumento de tamanho. A forma das partículas finas são circulares e compactas, enquanto os aglomerados tendem a ser mais alongados e apresentam superfície irregular. Os produtos aglomerados apresentaram melhores propriedades de instantaneização, ou maior dispersabilidade em água, em relação à matéria-prima, proveniente da secagem em spray dryer / Abstract: Fluid bed agglomeration is commonly used to improve the instant properties of spray-dried food powders. However, the fluidization of spray-dried particles is characterized by cracks and channels. Vibration or pulsation systems are frequently attached in the fluid bed equipments in order to improve the bed homogeneity and to allow the particles fluidization using lower fluidizing air flow. The aim of this work was to study the physical property modifications of soy protein isolate powder and acerola powder produced by a wetagglomeration process in a conical fluid bed, using fluidizing air pulsation for some runs. The equipment used was a batch-fluidized bed equipped with a rotating spherical valve installed below the air distribution plate that promotes the fluidizing air pulsation. Experimental designs and agglomeration kinetics were achieved in order to evaluate the optimal operational conditions and to study the particles growing behavior. The process variables studied were process time, fluidizing air temperature and velocity, atomized binder flow, atomization pressure, nozzle height and mass of sample. The product transformations were determined by an analysis of the particle diameter, size distribution, morphology and moisture content. During agglomeration, the raw particles coalesce, resulting in the formation of granules with increasing size, but morphological changes were also verified. The shape of the raw powder particles were circular and compact, while the agglomerated particles were elongated, wrinkled and showed tight solid bridges. The fluidization of spray-dried particles was enhanced with the pulsation system, resulting in higher fluid bed homogeneity and agglomerated products with narrows particle size distribution. The consolidation of small granules results in an improvement in the instant properties, increasing product wetting and dispersability in water / Doutorado / Doutor em Engenharia de Alimentos

Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-03-27T17:18:42Z No. of bitstreams: 2 Dissertação - Ellen Cristine Pineze Alonso - 2016.pdf: 3875444 bytes, checksum: a102742f77b4ed0806fe1d0733087998 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-28T11:05:04Z (GMT) No. of bitstreams: 2 Dissertação - Ellen Cristine Pineze Alonso - 2016.pdf: 3875444 bytes, checksum: a102742f77b4ed0806fe1d0733087998 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-03-28T11:05:04Z (GMT). No. of bitstreams: 2 Dissertação - Ellen Cristine Pineze Alonso - 2016.pdf: 3875444 bytes, checksum: a102742f77b4ed0806fe1d0733087998 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-03-31 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Introduction: Cyclodextrins have been used in several industries segments, mainly in the pharmaceutical industry. This material has been employed in the complexation of poorly soluble drugs with the aim to increase bioavailability and effect. Carvedilol (CARV) is a poor soluble drug used in the treatment of hypertension and congestive heart failure. Its oral bioavailability is reduced to β5%, due to their low aqueous solubility and first pass effect. Because of this, it is an excellent choice to form inclusion complexes with cyclodextrins. However, the use of cyclodextrins have some limitations, once it is necessary to use a large amount in the formulation and it can cause dilution of the drug and it can result in a solid oral form with inappropriate dimensions. Therefore, different strategies have been used to enhance complexation efficiency and reduce the amount of cyclodextrin, like the combination of the effect of drug ionization and inclusion complexes. In addition, the choice of the technique used to produce inclusion complexes is very important, because it is necessary to develop economic and effective techniques, which have been easily scalable to produce inclusion complexes in the industry. Spray drying technique have been extensively studied in cyclodextrin complexation, but this method is very expensive and presents lower efficiency. On the other hand, fluid-bed granulation has been widely used in the production of solid dosage forms but the use of this technique to produce cyclodextrin inclusion complexes is not described in the literature. Objective: The purpose of this study is to produce and characterize inclusion complexes containing carvedilol and cyclodextrin, using spray drying and fluidized bed techniques, with the aim to enhance drug dissolution rate. Material and methods: Phase solubility studies were performed using various cyclodextrins, in pH 1,β and 6,8, at room temperature, during 48 hours. Binary complexes were produced by spray drying and fluidized bed techniques. FTIR spectroscopy, DSC analysis, morphology, particle size, flowability and dissolution studies were performed to characterize the inclusion complexes. Results and discussion: Hidroxypropyl--cyclodextrin Cavitron W7 HP7 had the better solubility results. Thus, binary complexes CARV: HPCD prepared by spray drying and fluidized bed techniques in pH β,β showed better results and dissolution rate was 7 and 6 folds, respectively. However, solid dispersion prepared by fluid-bed presented better flowability indicating that this technique is the most appropriate for a large-scale production of solid dosage forms. Additionally, complexes containing HPȖCD showed good dissolution rate and could be considered as one more option for CARV complexation with great performance of inclusion complex formation in solid state. / Introdução: As ciclodextrinas têm sido amplamente utilizadas principalmente na indústria farmacêutica. Esses adjuvantes são usados na complexação de fármacos que apresentam baixa solubilidade aquosa, resultando em produtos com maior biodisponibilidade e portanto, efeito terapêutico superior. O carvedilol (CARV) é um fármaco pouco solúvel utilizado no tratamento da hipertensão e insuficiência cardíaca congestiva. Esse fármaco tem biodisponibilidade oral de apenas β5%, devido à sua baixa solubilidade aquosa e ao efeito de primeira passagem metabólica, sendo um excelente candidato a complexação com as ciclodextrinas. No entanto, o uso de ciclodextrinas em formas farmacêuticas sólidas é limitado pela necessidade de adicionar elevadas quantidades desses adjuvantes na formulação, o que ocasiona à diluição do fármaco e o aumento indesejado no tamanho da forma farmacêutica. Assim, diversas estratégias têm sido empregadas para aumentar a eficiência de complexação e reduzir a quantidade de ciclodextrina utilizada, como a ionização de fármacos associada a formação de complexos de inclusão. Outra preocupação importante é a seleção do método de complexação, pois é necessário desenvolver técnicas eficientes, econômicas e de fácil escalonamento visando a futura produção industrial dos complexos. O método de spray drying tem sido muito investigado para a obtenção de complexos com ciclodextrinas, mas apresenta baixa eficiência energética e custo elevado. Por outro lado, o método de leito fluidizado tem sido extensivamente utilizado na indústria farmacêutica, mas seu emprego como método de complexação durante a granulação de pós ainda não foi descrito na literatura. Objetivo: A proposta deste trabalho foi obter e caracterizar complexos de inclusão contendo carvedilol e ciclodextrinas, pelas técnicas de spray drying e leito fluidizado, visando melhorar a dissolução do fármaco a partir de formas farmacêuticas sólidas. Materiais e Métodos: Estudo de solubilidade de fases com diferentes tipos de ciclodextrinas foram realizados em soluções de pH 1,β e 6,8, sob temperatura ambiente, durante 48 horas. Complexos sólidos binários foram preparados pelas técnicas de spray drying e leito fluidizado. Os complexos de inclusão foram caracterizados por espectroscopia na região do infravermelho (FTIR), calorimetria exploratória diferencial (DSC), morfologia, tamanho de partícula, fluxo e avaliados quanto a dissolução do fármaco. Resultados e discussão: A ciclodextrina que apresentou melhor capacidade de solubilização do carvedilol foi a hidroxipropil-ȕ- ciclodextrina (HPȕCD) com maior grau de substituição (Cavitron W7 HP7). Complexos binários CARV: HPȕCD, preparados por spray drying e leito fluidizado, em pH β,β, apresentaram os melhores resultados, sendo o aumento na taxa de dissolução de 7 e 6 vezes, respectivamente. No entanto, a dispersão sólida preparada em leito fluidizado apresentou propriedades de fluxo superiores demonstrando que esta técnica é a mais adequada para a produção de formas sólidas em grande escala. Adicionalmente, os complexos contendo HPȖCD também apresentaram resultados de dissolução satisfatórios, sendo esta ciclodextrina modificada uma alternativa para a formação de complexos de inclusão contendo CARV.

Yes / A detailed steady-state catalytic-reforming unit (CRU) reactor process model is simulated in this work, and for the first time, different compressibility Z factor correlations have been applied using gPROMS software. The CRU has been modeled and simulated with the assumption that the gas phase behaves like an ideal gas. This is assumed for the four reactors in series and for different conditions of hydrogen–hydrocarbon ratio (HHR), operating temperature, and pressure. The results show that the Z factor varies at every point along the height of the reactors depending on reaction operating pressure, temperature, and HHR ratio. It also shows that the magnitude of deviation from ideal gas behaviour can be measured over the reactor height. The Z factor correlation of Mahmoud (J Energy Resour Technol Trans ASME 136:012903, 2014) is found to be suitable for predicting the Z factor distribution in the reactors.

"This research investigated the relationship between T5 heat treatment and elongation in thixocast and rheocast SSM components as a means to reduce the energy, time, and cost associated with T6 treatments while still producing improved properties over the as-cast condition. Temperature and time were varied as a part of work to optimize aging conditions for SSM materials. Both conventional furnace and fluidized bed heat treatments were employed. Tensile bars were fabricated from the heat treated A356 components and were pulled. Extensive SEM and stereo microscopy were performed to examine the factors which produced favorable results in the T5 condition. Data generated for T6 and as-cast components were also collected for purposes of comparison. Quality index calculations were employed to help evaluate the results. Optimized procedures and aging parameters have been presented"

O segmento farmacêutico demonstra um crescente interesse no processo de peletização, o qual consiste na aglomeração por via úmida de pós finos compostos de ativos e excipientes em pequenas unidades esféricas, com excelentes vantagens tecnológicas e terapêuticas. O objetivo do presente trabalho envolve o estudo de processos de incorporação de suspensões em péletes inertes, compostas de ativos e excipientes, utilizando dois tipos de processos: 1. Drageadeira Modificada e 2. Leito Fluidizado nas configurações top spray e bottom spray. Os ativos utilizados foram besilato de anlodipino nas concentrações de 2.5% e 5% em massa, e cloridrato de benazepril em 15% em massa, presentes nas formulações das suspensões e aplicadas em quantidades iguais nos dois processos, em um total de 9 lotes. Os indicadores de desempenho de processo utilizados para incorporação do ativo nos péletes inertes foram tempo de aplicação da suspensão (min) e taxa de aplicação da suspensão (g/min). Os péletes finais obtidos foram avaliados por meio das análises das propriedades físico-químicas: teor de umidade (%), teor de princípio ativo (%), uniformidade de conteúdo (%) e dissolução (%). Dentre os lotes testados, os processos em drageadeira e leito pelo sistema bottom spray apresentaram o menor tempo de aplicação (120 min) para a suspensão com o ativo anlodipino na concentração de 2.5%, enquanto que pelo sistema top spray apresentou um tempo de aplicação de 300 min, uma vez que este sistema foi projetado originalmente para processo de granulação. O processo em drageadeira apresentou a maior taxa real de aplicação, igual a 6.24 g/min, seguida pelo sistema bottom spray com 4.91 g/min, e o sistema top spray com 1.62 g/min, para suspensão com o ativo benazepril na concentração de 15%. Para os processos em drageadeira e leito pelo sistema bottom spray, todas as propriedades físico-químicas dos péletes deste estudo se apresentaram dentro dos padrões recomendados pela indústria farmacêutica, o que não aconteceu para o sistema top spray com relação à propriedade teor de princípio ativo (benazepril), cujo valor apresentado ficou em 12.90%, abaixo do limite inferior de 13.50%; o que não garantirá a eficácia do fármaco de acordo com a ação esperada. Os resultados apresentados ratificam os processos de peletização em drageadeira e leito pelo sistema bottom spray como os ideais pela técnica de incorporação de princípio ativo em péletes inertes. / The pharmaceutical industry has shown a growing interest in pelletization process, which consists of wet agglomeration of fine powders composed of active ingredients and excipients into small spherical unities, with excellent technological and therapeutic advantages. The objective of this work involves the study of processes of incorporation of suspensions in inert pellets, composed of active ingredients and excipients, using two types of processes: 1. Modified Coating Pan and 2. Fluid Bed in top spray and bottom spray systems. The active ingredients used were amlodipine besylate in concentrations of 2.5% and 5% by mass, and benazepril hydrochloride 15% by mass, included in the formulations of suspensions and applied in equal amounts in both processes, in a total of 9 batches. The process performance indicators used for incorporation of the active ingredient in inert pellets were time of application of the suspension (min) and rate of application of the suspension (g/min). The final pellets were evaluated by means of analyses of the physicochemical properties: water content (%), assay of active ingredient (%), uniformity content (%) and dissolution (%). Among the batches tested, the processes in coating pan and fluid bed by bottom spray system had the shortest application time (120 min) for the suspension with amlodipine besylate active with concentration of 2.5%, while the top spray system had an application time of 300 min, since this system was originally designed for granulation process. The process in coating pan showed the highest real rate of application, equal to 6.24 g/min, followed by the bottom spray system with 4.91 g/min, and the top spray system with 1.62 g/min to the suspension with benazepril hydrochloride with concentration of 15%. For the processes in coating pan and fluid bed by the bottom spray system, all physicochemical properties of the pellets of this study are presented within the standards recommended by the pharmaceutical industry, which has not happened for the top spray system with respect to property "assay of active ingredient (benazepril), whose value present was in 12.90%, below the lower limit of 13.50%, which does not guarantee the efficacy of the drug according to the expected action. The results presented confirm the processes of pelletization in coating pan and fluid bed by the bottom spray system as the ideal technique for incorporation of the active ingredient in inert pellets.