Orientador: Míriam Dupas Hubinger / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-17T11:13:22Z (GMT). No. of bitstreams: 1 RodriguezDiaz_JulioCesar_M.pdf: 3275088 bytes, checksum: 4baa128a0e7dc07566683d567b97b97c (MD5) Previous issue date: 2011 / Resumo: O presente trabalho teve como objetivo a obtenção de hidrolisado protéico de pele de cação em pó pelos processos de hidrólise enzimática e secagem por atomização. Na primeira etapa, foi estudado o processo de hidrólise utilizando a enzima comercial ProtamexTM, visando a otimização do processo para a recuperação de peptídeos de baixo peso molecular. A influência da temperatura, do pH e da relação Enzima/Substrato sobre o grau de hidrólise, recuperação de proteína e cinética enzimática foram avaliadas. As condições ótimas de processo foram fixadas em: 51 °C, 4,0% p/p de enzima e pH 7,1. Nessas condições, o hidrolisado obtido foi caracterizado em termos de composição química, composição de aminoácidos e distribuição de tamanho de peptídeo. O grau de hidrólise atingiu 19,3%, recuperou-se 90,3% do total da proteína presente na matéria-prima e o peso molecular foi inferior a 6,5 kDa. Na segunda etapa do projeto, foi avaliada a influência das variáveis do processo de secagem por atomização sobre as propriedades físico-químicas e antioxidantes do hidrolisado protéico de pele de cação em pó, usando maltodextrina (DE=10) como agente carreador. A temperatura do ar e a concentração de agente carreador foram variadas. As respostas analisadas foram a umidade final, a atividade de água, a densidade aparente, a higroscopicidade, o tamanho de partícula e a capacidade antioxidante, determinada pelos métodos de redução do íon férrico (FRAP) e captura do radical catiônico ABTS+0 (TEAC). Os resultados mostraram que a adição de maltodextrina contribuiu significativamente para obtenção de partículas com menor umidade e higroscopicidade e maiores tamanhos de partícula e densidade aparente. Além disso, quanto maior foi a concentração de maltodextrina adicionada, maiores foram os valores de capacidade antioxidante, provavelmente devido à formação de compostos de Maillard durante a secagem / Abstract: The objetive of the present work was to obtain a shark skin protein hydrolysate powder by enzymatic hydrolysis and spray drying. In the first part of this work was studied the enzymatic hydrolysis process by using the commercial enzyme ProtamexTM, aiming the process optimization for recovery of low molecular weight peptides. The influence of temperature, pH and Enzyme/Substrate ratio on the degree of hydrolysis, protein recovery and enzymatic kinetics was evaluated. Optimal conditions were established at: 51°C, 4.0% p/p of enzyme and pH of 7.1. At these conditions, protein hydrolysate was characterized with respect to chemical composition, amino acid composition and peptide size distribution. Degree of hydrolysis achieved 19.3%, 90.3% of total protein was recovered and peptide size was lower than 6,5 kDa. In the second part of the project, the influence of spray drying variables process on physicochemical and antioxidant properties of shark skin protein hydrolysate powders, using maltodextrin (DE=10) as a carrier agent, was evaluated. Air temperature and maltodextrin concentration were varied. The responses analyzed were the final moisture content, water activity, bulk density, hygroscopicity, particle size distribution and antioxidant capacity determined by ferric reduction antioxidant power (FRAP) and ABTS+0 radical cation capture (TEAC) assays. Results showed that maltodextrin addition significantly contributed to obtaining particles with less moisture content, lower hygroscopicity and higher particle size and bulk density. Besides, antioxidant capacity was increased as increasing of maltodextrin concentration, probably due to the formation of Maillard compounds during drying process / Mestrado / Mestre em Engenharia de Alimentos

Orientadores: Miriam Dupas Hubinger, Catherine Brabet / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-13T22:27:20Z (GMT). No. of bitstreams: 1 Tonon_RenataValeriano_D.pdf: 4726110 bytes, checksum: c1e07b92e67333944d2bab593af0c20d (MD5) Previous issue date: 2009 / Resumo: O presente trabalho teve como objetivo a obtenção do suco de açaí em pó pelo processo de spray drying. Inicialmente, avaliou-se a influência das condições de processo sobre a umidade, higroscopicidade, a retenção de antocianinas e o rendimento do processo, através de um delineamento composto central rotacional 23 completo. A partir das condições selecionadas nessa primeira etapa (temperatura de secagem de 140ºC, vazão mássica de 15g/min e 6% de agente carreador), foram produzidas partículas utilizando quatro diferentes tipos de agentes carreadores: maltodextrina 10DE, maltodextrina 20DE, goma arábica e fécula de mandioca. Essas partículas foram então submetidas a uma caracterização físico-química, sendo analisadas em relação às seguintes propriedades: umidade, atividade de água, densidade, porosidade, solubilidade, molhabilidade, distribuição do tamanho de partículas, morfologia, cor, polifenóis totais, antocianinas e atividade antioxidante. As amostras produzidas com maltodextrina 20DE e com goma arábica apresentaram maiores valores de umidade e atividade de água, e menor tamanho de partículas., enquanto as produzidas com fécula de mandioca apresentaram menor solubilidade e porosidade e maior densidade aparente e molhabilidade, maior diâmetro médio e maior perda de polifenóis e antocianinas durante o processo de secagem. Em seguida, avaliou-se a estabilidade destas partículas, quando expostas a diferentes umidades relativas, através da construção de isotermas de sorção e da determinação da temperatura de transição vítrea. As amostras produzidas com fécula de mandioca foram apresentaram menor higroscopicidade, seguidas pelas produzidas com maltodextrina 10DE. A temperatura de transição vítrea diminuiu com o aumento do teor de umidade das amostras, confirmando o efeito plasticizante da água sobre esta propriedade. Por fim, realizou-se um estudo da estabilidade das antocianinas e da atividade antioxidante nos pós estocados em diferentes condições de temperatura e umidade relativa. O aumento nessas duas condições resultou em uma maior degradação das antocianinas. A atividade antioxidante das amostras também diminuiu com o aumento da umidade relativa, mas aumentou com o aumento da temperatura de estocagem. As partículas produzidas com maltodextrina 10DE foram as que apresentaram maiores tempos de meia-vida, seguidas pelas produzidas com goma arábica / Abstract: The objective of this work was to obtain a powdered açaí juice by spray drying. The influence of process conditions on the moisture content, hygroscopicity, anthocyanin retention and process yield was evaluated using a 23 experimental design. From the conditions selected in this first section, (inlet air temperature of 140ºC, feed flow rate of 15 g/min and 6% of carrier agent), particles were produced with four types of carrier agents: maltodextrin 10DE, maltodextrin 20DE, gum Arabic and tapioca starch. These particles were then characterized with respect to moisture content, water activity, density, porosity, solubility, wettability, particles size distribution, morphology, color, total polyphenolics, anthocyanin content and antioxidant activity. The samples produced with maltodextrin 20DE and with gum Arabic exhibited the highest moisture content and water activity, and the lowest particles size. The particles produced with tapioca starch were the less soluble, less porous and with the lowest bulk density and wettability, highest mean diameter and highest poliphenolic and anthocyanin loss, during the spray drying process. Particles stability, when exposed to different relative humidities, was evaluated through the construction of sorption isotherms and determination of the glass transition temperature. The samples produced with tapioca starch were the less hygroscopic, followed by those produced with maltodextrin 10DE. Glass transition temperature decreased with increasing moisture content, confirming the plasticizant effect of water on this property. Finally, a study about anthocyanin stability and antioxidant activity of powders stored at different temperatures and relative humidities was carried out. The increase of both these conditions resulted in higher anthocyanin degradation. The antioxidant activity also decreased with increasing relative humidity, but increased with increasing temperature. The particles produced with maltodextrina 10DE showed the highest half-life followed by those produced with gum Arabic / Doutorado / Doutor em Engenharia de Alimentos

Orientadores: Florencia Cecilia Menegalli, Miriam Dupas Hubinger / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-15T07:55:14Z (GMT). No. of bitstreams: 1 Machado_VanessaGoulart_M.pdf: 4523027 bytes, checksum: f852899c05d9342769d277f2255a6d51 (MD5) Previous issue date: 2010 / Resumo: Este trabalho teve como objetivo a obtenção de tomate em pó através do processo de secagem por atomização da polpa de tomate. Os experimentos foram conduzidos utilizando um atomizador de bancada e maltodextrina 10DE foi empregada como agente carreador. Foi utilizado um delineamento central composto rotacional (DCCR) para estudar a influência das seguintes variáveis independentes: temperatura do ar de secagem (153 a 187 °C), vazão de alimentação (0,57 a 0,83 l/h) e concentração de maltodextrina (3,3 a 11,7%). As variáveis de resposta foram o rendimento de produto e as seguintes características do tomate em pó: diâmetro médio de partícula, conteúdo de umidade, atividade de água, densidade do leito, higroscopicidade, solubilidade, tempo de instantaneização, retenção de carotenóides e retenção de ácido ascórbico. Os pós de tomate também foram caracterizados quanto à distribuição de tamanho de partículas e cor. Todas as variáveis mostraram influência significativa sobre as características do produto em pó, sendo que a concentração de maltodextrina foi a variável com efeito significativo sobre a maioria das respostas (rendimento, diâmetro médio de partícula, umidade, densidade do leito, higroscopicidade, tempo de instantaneização, retenção de carotenóides e retenção de ácido ascórbico), além de sua interação com a temperatura do ar de secagem. A análise das superfícies de resposta indicou que a produção de um pó com menor conteúdo de umidade, higroscopicidade, tempo de instantaneização e maior retenção de carotenóides pode ser conseguida utilizando-se temperatura do ar de secagem de 160 °C, vazão de alimentação de 0,62 l/h e concentração de maltodextrina de 10%, considerando a polpa de tomate com 5% de sólidos totais. Para as demais respostas (rendimento, diâmetro médio de partícula, atividade de água, densidade aparente, solubilidade e retenção de ácido ascórbico), os modelos obtidos não foram estatisticamente significativos, dentro da faixa de valores utilizada para cada variável independente do planejamento experimental. O tomate em pó obtido por atomização apresentou grande potencial de utilização, devido às suas propriedades como solubilidade e alta retenção de ácido ascórbico, além do baixo conteúdo de umidade e atividade de água, que facilitam seu armazenamento e transporte / Abstract: The objective of this work was to obtain tomato powder by spray drying of tomato pulp. The process was carried out using a laboratory spray dryer and maltodextrin 10DE was used as carrier agent. A central composite rotatable design (CCRD) was used to estimate the influence of the following independent variables: inlet air temperature (153 to 187 °C), feed flow rate (0.57 to 0.83 l/h) and maltodextrin concentration (3.3 to 11.7%) on the product yield and on the powder properties of the powder. The evaluated characteristics in tomato powder were: mean diameter, moisture content, water activity, bulk density, hygroscopicity, solubility, wetting time, carotenoids retention and ascorbic acid retention. Tomato powder was also characterized for particle size distribution and color. All variables had significant influence on the characteristics of the tomato powder and the maltodextrin concentration was the variable with significant effect on most of the responses (product yield, mean diameter, moisture content, bulk density, hygroscopicity, wetting time, carotenoids retention and ascorbic acid retention), besides its interaction with the inlet air temperature, at a 90% confidence interval. The response surface analysis indicated that obtaining a product with lower moisture content, lower hygroscopicity, lower wetting time and higher carotenoids retention can be achieved by using the inlet air temperature of 160 °C, feed flow rate of 0.62 l/h and maltodextrin concentration of 10%, considering the tomato pulp with 5% total solids. For the responses: process yield, mean diameter, water activity, bulk density, solubility and ascorbic acid retention, the models obtained were not statistically significant, within the levels used for each independent variable in experimental design. Tomato powder, obtained by spray drying, showed a great potential to several applications, due to its properties such as solubility and high ascorbic acid retention, besides the low moisture content and water activity that facilitate its storage and transport / Mestrado / Mestre em Engenharia de Alimentos

O objetivo desse trabalho foi obter polpa de guavira desidratada por atomização, utilizando maltodextrina ou goma arábica como agentes carreadores. Inicialmente, avaliou-se a influência das condições de processo, temperatura do ar de secagem (130, 155 e 180) °C e vazão volumétrica da mistura (20 e 40) mL/min, o tipo e concentração de agente carreador (10 e 20) % nas características físicas, físico-químicas e atividade antioxidante do produto obtido. As propriedades analisadas foram umidade, atividade de água, higroscopicidade, solubilidade, cor, distribuição e tamanho médio de partículas, morfologia, compostos fenólicos totais e atividade antioxidante. A temperatura do ar de secagem e a vazão volumétrica de alimentação influenciaram significativamente todas as propriedades da guavira em pó. A umidade e atividade de água apresentaram os menores valores na temperatura intermediária, independentemente do tipo e concentração do carreador usado. A solubilidade das amostras adicionadas de maltodextrina foram superiores às amostras com goma arábica. O aumento da concentração de agente carreador, em geral, proporcionou um aumento no parâmetro L* e diminuição dos parâmetros a* e b*, tornando as amostras mais claras e reduzindo as tonalidades vermelha e amarela. A guavira em pó apresentou coloração próxima do amarelo e marrom, com grande variação nos parâmetros de cor C* e H* em função das diferentes condições de secagem. A distribuição do tamanho de partículas não teve um padrão definido e o tamanho médio das amostras com maltodextrina foram maiores do que as com goma arábica para a temperatura do ar a 130 °C. No entanto, para as outras temperaturas (155 e 180) °C não houve um comportamento específico do tamanho das partículas em função da vazão de alimentação, tipo e ou concentração de agente carreador. A análise de microscopia eletrônica de varredura permitiu observar que as partículas obtidas tanto com maltodextrina como goma arábica apresentaram formato esférico, superfície rugosa e com adesão de partículas menores nas de maior tamanho, sendo que a superfície das partículas com goma arábica também apresentaram concavidades. A atividade antioxidante foi superior quando utilizada a temperatura de secagem intermediária. A partir das condições selecionadas na primeira etapa (temperatura do ar de 155 °C, vazão volumétrica da mistura de 40 mL/min e 10% de maltodextrina ou goma arábica) a polpa de guavira em pó foi caracterizada quanto a temperatura de transição vítrea, as isotermas de adsorção e a estabilidade à estocagem do ácido ascórbico, compostos fenólicos totais e da atividade antioxidante da polpa de guavira em pó produzida por spray drying ao longo de 120 dias. As temperaturas de transição vítrea foram de (25,2 ± 2,7 °C e 31,4 ± 0,4) °C para os pós produzidos com goma arábica e maltodextrina, respectivamente. O modelo de BET apresentou ajuste muito bom (R2>0,99) para descrever o comportamento de sorção de água das amostras nas temperaturas de (20, 30 e 40) °C. A polpa de guavira em pó produzida com goma arábica apresentou maior adsorção de água do que as amostras obtidas com maltodextrina. No estudo da estabilidade, as amostras foram acondicionadas em embalagem de polietileno laminado e armazenadas a 25 °C e umidade relativa de 75%. A embalagem de polietileno laminado foi eficiente na manutenção do teor de ácido ascórbico e atividade antioxidante da guavira em pó por um período de 120 dias, independente do carreador adicionado. O teor de compostos fenólicos para a guavira em pó com goma arábica apresentou uma redução nos primeiros 22 dias, contudo a amostra com maltodextrina manteve-se estável durante 120 dias de armazenamento. / The aim of this work was to obtain dried guavira pulp by spray drying, using maltodextrin or arabic gum as carrier agents. Initially, it was evaluated the influence of the process conditions, inlet air temperature (130, 155 e 180) °C and mixture feed flow rate (20 e 40) mL/min, carrier agent type and concentration (10 e 20) % in physical, physicochemical properties and antioxidant activity of the product. The analyzed properties were moisture content, water activity, higroscopicity, solubility, distribution and average particle size, morphology, total phenolic compounds and antioxidant activity. The inlet air temperature and mixture feed flow significantly influenced all the properties of guavira powder. The moisture content and water activity showed lower values in intermediate temperature, independent of the carrier agent type and concentration. The solubility of the samples with maltodextrin were higher than the samples with arabic gum. Increasing the carrier agent concentration generally resulted in an increase of the parameter L* and a reduction of a* and b* parameters, making lighter samples and reducing the red and yellow hues. The color of the guavira powder presented next to yellow and brown coloring, with great variation in parameters C* and H* depending on the different drying conditions. The size distribution of the particles had no definite pattern and the particles average size of the samples with maltodextrin were higher the samples with arabic gum for the inlet air temperature at 130 °C. However, for the other temperatures (155 and 180) °C there is a specific behavior of the particle size depending of the feed flow rate, carrier agent type and concentration. The scanning electronic microscopic analysis observed that the particles obtained with maltodextrin or arabic gum presented spherical, roughness surface and adhesion of the smaller particles into larger, the particles with arabic gum also presented concavities. The antioxidant activity was higher at intermediate inlet air temperature. From the selected conditions at the first phase (inlet air temperature of 155 °C, feed flow rate of 40 mL/min and 10% of maltodextrina or arabic gum) the guavira pulp powder were evaluated the glass transition temperature, the adsorption isotherms and the storage stability of ascorbic acid and antioxidant activity of the guavira powder produced to over 120 days. The glass transition temperatures were (25,2 ± 2,7 °C e 31,4 ± 0,4) °C for the powder obtained with arabic gum and maltodextrin, respectively. The BET model presented good adjustment (R²>0,99) to describe the water sorption behavior of the samples at test temperatures of (20, 30 e 40) °C. The guavira powder with arabic gum showed higher water adsorption than the samples with maltodextrin. In the stability study, samples were packed in polyethylene-laminated packaging and stored at 25 °C and relative humidity of 75%. The packaging was effective in maintaining ascorbic acid and antioxidant activity of the guavira powder for a period of 120 days for samples with the addition of maltodextrin and gum arabic. The content of phenolic compounds for guavira powder with gum arabic showed a reduction in the first 22 days, but the sample with maltodextrin remained stable for 120 days of storage.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / As indÃstrias de frutas tÃm sofrido pressÃes para se adaptar aos crescentes requerimentos dos consumidores, relacionados a conveniÃncia, seguranÃa alimentar, e benefÃcios à saÃde. Uma evidÃncia de tais mudanÃas à o aumento da produÃÃo de sucos de frutas e produtos similares. Embora os nÃctares, prontos para beber, sejam produtos de conveniÃncia, eles tÃm alto peso e volume, jà que tÃm a Ãgua como principal componente. Esse à um aspecto inconveniente, e aumenta os custos de transporte. Os sucos em pà tÃm algumas vantagens sobre os sucos integrais, como o transporte mais fÃcil e barato e sua maior estabilidade microbiolÃgica. No entanto, o consumidor parece ainda confundir sucos em pà com refrescos artificiais em pÃ, mais comumente encontrados, o que prejudica a consolidaÃÃo dos primeiros no mercado. O caju (Anacardium occidentale) à uma fruta originÃria do Nordeste brasileiro, para o qual apresenta grande importÃncia socioeconÃmica. à formado por castanha (verdadeiro fruto) e pedÃnculo (pseudofruto). A alta perecibilidade do pedÃnculo in natura tem motivado o desenvolvimento de processos que gerem produtos estÃveis, disponÃveis ao longo do ano, ao mesmo tempo facilitando seu transporte para longe da regiÃo produtora. A atomizaÃÃo à a tÃcnica mais utilizada para secagem de alimentos lÃquidos. Entretanto, produtos ricos em aÃÃcares, como sucos de frutas, sÃo difÃceis de atomizar, pois produzem pÃs muito higroscÃpicos, suscetÃveis a aglomeraÃÃo. Isso pode ser minimizado pela adiÃÃo dos chamados adjuvantes de secagem, como as maltodextrinas, que reduzem sua higroscopicidade. O presente estudo envolveu uma tentativa de substituiÃÃo (total ou parcial) de maltodextrinas (MD) por goma de cajueiro (GC), um polissacarÃdeo semelhante à goma arÃbica, muito abundante no Nordeste brasileiro, mas ainda pouco utilizada. O objetivo do trabalho foi avaliar o impacto de duas variÃveis do processo de atomizaÃÃo - proporÃÃo adjuvante de secagem/ sÃlidos de caju (2:1-5:1) e grau de substituiÃÃo de MD por GC (0-100%), segundo um delineamento composto central - sobre a retenÃÃo de Ãcido ascÃrbico e as propriedades fÃsicas (higroscopicidade e fluidez) e solubilidade de suco de caju atomizado. A retenÃÃo de Ãcido ascÃrbico durante a atomizaÃÃo foi favorecida por maiores proporÃÃes adjuvante de secagem/sÃlidos de caju (AS/SC) e maior grau de substituiÃÃo de MD por GC. A goma de cajueiro mostrou-se um material bastante promissor a ser utilizado como adjuvante de secagem. As condiÃÃes de processo consideradas como as mais adequadas foram as seguintes: proporÃÃo AS/SC, 5:1, com substituiÃÃo de MD por GC em pelo menos 50%. / The fruit industries have been compelled to adapt to the increasing consumer requeriments related to convenience, food safety and health benefits. An evidence of such changes is the increasing production of fruit juices and related products. Although the ready-to-drink fruit nectars are convenience products, they have high weight and volume, since they have water as their main component. This is an inconvenient aspect, and increases transportation costs. The powder juices have some advantages over whole juices, such as easier and cheaper transportation and higher microbial stability. However, the consumers seem to confuse powder juices with the more commonly found fruit-flavored powder drinks, impairing the consolidation of the former in the market. Cashew (Anacardium occidentale) is a fruit from Brazilian Northeast, having great socio-economic importance for that region. It contains the cashew nut (the real fruit) and the cashew apple (pseudofruit). The low stability of the fresh cashew apple has motivated the development of processes to obtain more shelf-stable products which could be available all year long, and at the same time easy to transport to distant markets. Spray drying is the most used technique to dry liquid foods. However, sugar-rich foods such as fruit juices are difficult to dry, since they produce too hygroscopic powders, which are prone to caking and flowing problems. This can be minimized by addition of drying-aids, such as maltodextrins, which reduce their hygroscopicity. The present study involved an attempt to totally or partially replace maltodextrins (MD) by cashew tree gum (CTG), a polysaccharide similar to gum arabic, very abundant in Brazilian Northeast but under-utilized. The objective of the work was to evaluate the impact of two variables â drying aid/cashew apple solids (DA/CA) ratio (2:1-5:1) and degree of replacement of MD with CTG (0-100%), according to a central composite design â on ascorbic acid retention, physical properties (hygroscopicity and flowability) and solubility of spray dried cashew apple juice. The ascorbic acid retention was favored by higher DA/CA ratios and higher replacements of MD. Cashew tree gum was shown as a promising drying aid material. The most adequate drying conditions were considered as being the following: DA/CA ratio, 5:1, with CTG replacing MD in at least 50%.

Orientador: Rafael Augustus de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Agrícola / Made available in DSpace on 2018-08-22T14:02:42Z (GMT). No. of bitstreams: 1 Martin_LuizGabrielPereira_M.pdf: 2465863 bytes, checksum: 1a0cdd139b75ba72f4fd72913745ee3f (MD5) Previous issue date: 2013 / Resumo: O cupuaçu (Theobroma grandiflorum Schum.) tipicamente amazônico apresenta polpa ácida (com bastante vitamina C), sabor agradável e de aroma característico. Sua característica exótica vem conquistando cada vez mais adeptos, tendo grande potencial comercial e merecendo a atenção da comunidade científica. A secagem da polpa de cupuaçu por atomização é uma excelente alternativa para conservar e garantir o comércio do fruto em períodos de entressafra. O objetivo deste trabalho é a avaliação da secagem de polpas de cupuaçu comercial e in natura por meio do processo de secagem por atomização, utilizando como agente carreador a maltodextrina 10DE. Inicialmente, foram determinadas as composições centesimais das matérias-primas. Testes preliminares foram realizados para definir a faixa de valores dos parâmetros operacionais utilizados no processo de secagem. A partir disso, um planejamento experimental - delineamento composto central rotacional (DCCR) avaliou a influência das variáveis independentes temperatura de entrada do ar no secador (variando de 90 à 160ºC) e a concentração de maltodextrina (variando de 5 a 30%) nas respostas rendimento de secagem, teor de água, higroscopicidade, atividade de água, vitamina C, pH, açúcares redutores, açúcares totais e cor para ambos os tipos de polpa. Por meio da metodologia de superfície de resposta, foram obtidas as condições otimizadas do processo (temperatura de secagem de 155ºC e 28,2% de maltodextrina) iguais para ambas às polpas. Com isso foi feita a validação dos modelos matemáticos. As partículas obtidas nas condições ótimas foram avaliadas quanto à densidade aparente, densidade absoluta, porosidade, distribuição do tamanho de partícula e microscopia eletrônica de varredura. Os modelos das respostas: teor de água, higroscopicidade, vitamina C, açúcares redutores, açúcares totais e cor, da polpa de cupuaçu comercial foram significativos com coeficiente de determinação R2 de 71,57%, 92,18%, 85,11%, 93,76%, 93,76% e 81%, respectivamente. Para a polpa de cupuaçu in natura foram significativos os modelos das respostas: teor de água, higroscopicidade, rendimento, atividade de água, vitamina C, pH, açúcares redutores, com R2 de 93,83%, 94,23%, 71,33%, 83,99%, 82,27%, 73,66% e 76,44%, respectivamente. As partículas da polpa in natura tiveram densidade menor resultando em uma maior porosidade comparando com a polpa comercial, com diâmetro médio de 9,1 e 8,96 ?m, respectivamente. A morfologia da partícula resultante da amostra in natura apresentou-se com menos aglomerações e com superfícies mais lisas em comparação com a amostra comercial. As partículas produzidas de polpa de cupuaçu in natura foram as que apresentaram maior preservação dos teores de vitamina C e melhor estrutura na encapsulação / Abstract: Cupuassu (Theobroma grandiflorum Schum.) is a typically Amazonian fruit which presents acidic pulp (with enough Vitamin C), pleasant taste and distinctive aroma. Its exotic characteristic is gaining more and more followers, with great commercial potential and deserving the attention of scientific community. Cupuassu pulp spray drying is a great alternative to support and ensure the fruit trade in off-season periods. The objective of this research work is the evaluation of commercial and fresh cupuassu pulp drying by spray drying process, using as maltodextrin 10DE encapsulating agent. Initially, raw materials compositions were analyzed. Preliminary tests were performed in order to set the range of operational parameters which were used in experimental runs. Then, an experimental design - central composite rotational design (CCRD) - was performed to evaluated the influence of independent variables inlet air temperature (ranging from 90 to 160 ºC) and maltodextrin concentration (range 5-30%) on the responses drying yield, moisture content, hygroscopicity, water activity, vitamin C, pH, reducing sugars, total sugars and color for both kind of cupuassu pulp. By response surface methodology, we obtained the optimized process conditions (drying temperature of 155 ºC and 28.2% maltodextrin) which are the same for the both pulps. After that, the mathematical models were validated. The particles obtained in optimum conditions were evaluated for bulk density, absolute density, porosity, and particle size distribution and scanning electron microscopy. For commercial cupuassu pulp, the models of the responses moisture content, hygroscopicity, vitamin C, reducing sugars, total sugars and color were significant with determination coefficient R2 of 71.57%, 92.18%, 85.11%, 93, 76%, 93.76% and 81%, respectively. For fresh cupuassu pulp, the models of responses moisture content, hygroscopicity, yield, water activity, vitamin C, pH, reducing sugars were significant with R2 of 93.83%, 94.23%, 71, 33%, 83.99%, 82.27%, 73.66% and 76.44%, respectively. The powder from the fresh pulp presented lower density resulting in a higher porosity in comparison with the commercial pulp powder, with a mean diameter of 9.1 and 8.96 ?m, respectively. The particle morphology of the fresh pulp powder presented with fewer agglomerated particles and smoother surfaces compared to the commercial pulp powder. The particles produced from fresh cupuassu pulp showed higher preservation of vitamin C and better structure in the encapsulation / Mestrado / Tecnologia Pós-Colheita / Mestre em Engenharia Agrícola

La cristallisation par effet anti-solvant, comme technique de production de micro/nanoparticules, présente certains inconvénients. En effet, pour des molécules nouvellement synthétisées ou découvertes, comme le LASSBio-294, les solubilités dans l'eau et dans les solvants organiques sont faibles ce qui limite l'application de cette opération. L'utilisation de solvants alternatifs ouvre de nouvelles perspectives de recristallisation de ce type de molécules. Dans ce travail, nous nous sommes intéressés à la cristallisation du LASSBio-294 en utilisant un liquide ionique comme solvant. Ce sont des sels organiques fondus à température ambiante, qui ont la particularité d’avoir une tension de vapeur nulle. Ils constituent une nouvelle classe de solvants non volatiles et ininflammables qui présentent des propriétés originales. Dans un premier temps, des liquides ioniques (LIs) dérivés du cation imidazolium ont été utilisés comme solvant alternatif. La solubilité a été mesurée dans 5 LIs,dans l’eau et dans des mélanges eau/LI. Dans l’eau pure la solubilité est très faible (5 ppm). En revanche, dans certains LIs, elle est supérieure à 200 mg/g solution. Les résultats de solubilité dans des mélanges eau/LI ont permis de choisir le rapport eau/LI pour l’obtention d’un bon rendement en solide. En complément, une étude de la stabilité du solide en suspension a été menée dans différents systèmes aqueux. Cette étude a montré sa possible hydrolyse. Dans un deuxième temps, la recristallisation a été réalisée avec le 1-éthyl-3-méthylimidazolium méthyl phosphonate [emim][CH3O(H)PO2] comme solvant et l’eau comme anti-solvant. Deux approches sont présentées en vue de favoriser le mélange : l'utilisation de dispositifs de mélange et l'introduction des ultrasons pendant le processus de cristallisation. L’influence de paramètres tels que le rapport anti-solvant/solvant, la concentration initiale et la présence d'additifs a été étudiée. Les solides formés puis séchés en étuve ont été caractérisés par granulométrie laser, microscopie électronique à balayage, diffractométrie de rayons X, calorimétrie différentielle à balayage et test de dissolution. Malgré une diminution de la taille des particules élémentaires, l'état d'agglomération des cristaux obtenus n'a pas permis une augmentation de la vitesse de dissolution. En modifiant le mode de séchage (séchage par atomisation), cette agglomération est réduite et la dissolution améliorée. De plus, la présence d'un polymère entérique en solution lors du séchage par atomisation des cristaux synthétisés a eu un effet notable sur la structure des agglomérats formés. Ces derniers peuvent se désagréger, se disperser et se dissoudre rapidement. / The anti-solvent crystallization allows obtaining micro/nanoparticles, but it presents some disadvantages. In the case of new pharmaceutical molecules, as the LASSBio-294, the solubility in water or organic solvents is very low limiting the application of this operation. The use of Ionic Liquids (ILs) as alternative solvents opens new perspectives in pharmaceutical processing through anti-solvent crystallization process. Unlike conventional solvents, ILs are entirely composed of ions. ILs are organic salts, usually liquid at room temperature, and which are composed of a relatively large asymmetric organic cation and of an inorganic or organic anion. ILs derived from imidazolium cation are used as alternative solvents for this drug, water being used as anti-solvent. First, the solubility is measured in 5 ILs, in water and in water/IL mixtures. In pure water, the solubility is very low (5 ppm). However, for some ILs, it is greater than 200 mg/g solution. The results of solubility in water/IL mixtures permit to choose a water/IL ratio leading to a good solid theoretical yield. Then recrystallization is performed with 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] as the preferred solvent. Antisolvent crystallization represents a class of process characterized by the mixing between a solution and an antisolvent to produce solid particles. The influence of solvent/anti-solvent ratio, initial concentration, and additives is studied. The solids formed and dried in an oven are characterized by laser granulometry, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and dissolution test. Despite the decrease of elementary particles size, the agglomeration state of particles does not permit to improve the dissolution rate. The agglomeration is reduced and the dissolution improved by modifying the drying process (spray drying). Moreover, the presence of an enteric polymer during the spray drying process has a significant impact on the structure of the formed agglomerates. These are disaggregated, dispersed and dissolved very quickly.

L’amélioration de la solubilité des principes actifs peu solubles est devenue l’un des principaux challenges de l’industrie pharmaceutique. Bien que présentant une structure chimique potentiellement idéale pour interagir avec la cible, elles échouent dans l’efficacité in vivo : après administration, elles ne peuvent se dissoudre dans les milieux aqueux biologiques et par conséquent ne peuvent être transportées sur leur site d’action pour atteindre la concentration efficace, amenant à un échec thérapeutique. De nombreuses stratégies très intéressantes ont été proposées pour surmonter ce sérieux obstacle. Les dispersions solides sont étudiées depuis plus de 40 ans et ont conduit à de très nombreuses publications mais jusqu’à aujourd’hui peu de produits ont été commercialisés principalement pour des raisons de stabilité physico-chimique. Celles-ci ont pour but de présenter le principe actif sous sa forme amorphe car cette forme solide présente un état d’énergie plus élevé et par conséquent une solubilisation facilitée. Par ailleurs, le système doit rester stable durant le stockage, ainsi la recristallisation ou tout autre changement entraînant une modification du profil de libération doivent être évités. Différentes techniques de production peuvent être utilisées pour préparer les dispersions solides comme l’extrusion à chaud ou l’atomisation-séchage. Le principal objectif de ce travail a été d’améliorer la solubilité de l’Efavirenz (EFV), un principe actif peu soluble dans l’eau, par sa dispersion dans une matrice polymère en utilisant la technique d’atomisation-séchage. Différents polymères ont été utilisés : Soluplus®, PVPVA64 et HPMCAS. Des mélanges binaires EFV-polymère (Soluplus®, PVPVA64 et HPMCAS) ont été générées et caractérisées. Les techniques de caractérisation utilisées ont été la calorimétrique différentielle modulée, la diffraction des rayons X, l’analyse Raman et la spectroscopie infrarouge à transformée de Fourier et l’analyse de sorption de vapeur pour la caractérisation physicochimique de l’état solide des mélanges binaires. L’étude de caractérisation a été complétée par une étude de solubilité et de dissolution dans différents milieux aqueux ainsi que de stabilité dans différentes conditions de stress de température et humidité relative. Les résultats ont mis en évidence la formation de dispersions solides amorphes avec les trois polymères utilisés. Les différents profils de libération obtenus à partir des mélanges binaires générés dans ce travail montrent l’influence du type de polymère, de la concentration du principe actif dans les dispersions solides et de la composition du milieu de dissolution sur la fonctionnalité des produits (solubilité, dissolution). / Poor aqueous solubility has become a property of numerous new drug candidates causing major concern. Despite a potentially ideal chemical structure allowing for interaction with the target, these substances fail to be effective in vivo: upon administration, they cannot dissolve sufficiently in the aqueous fluids of the body and, thus, cannot be transported to their site of action to reach therapeutically effective concentrations. Various interesting strategies have been proposed to overcome this crucial hurdle. Solid dispersions have been studied for more than 40 years and lead to numerous interesting research articles. However, today, only a few products have reached the market principally due to problems with the physico-chemical stability. The idea is to transform the crystalline raw material into a physical state having a greater energy in order to increase the driving force for drug dissolution. At the same time, the system should be stable during long term storage, thus, re-crystallization or other system changes, resulting in altered drug release rates, must be avoided. Different manufacturing techniques can be used to prepare such polymeric systems, including hot-melt extrusion and spray-drying. The main objective of this work has been to improve Efavirenz (EFV) solubility by forming solid dispersions using the spray-drying technique. In this study EFV has been incorporated into hydrophilic polymeric matrices Soluplus®, PVPVA64 and HPMCAS to increase its aqueous solubility. Binary mixtures EFV-Soluplus®, EFV-PVPVA64 and EFV-HPMCAS) were produced and characterized using SEM, X-ray diffraction, DSC, RAMAN, Infrared spectroscopy and water vapor sorption. This physicochemical characterization was completed by solubility and in vitro dissolution studies at different stress conditions (temperature, RH). The results obtained confirmed the formation of amorphous solid dispersions for all studied drug-polymer combinations. The different kinetic profiles obtained from the various solid dispersions generated in this work showed the influence of the type and polymer and drug-polymer binary mixture composition and in vitro dissolution medium on the functionality of spray-dried solid dispersions produced in this work (solubility and dissolution kinetics).

Among the different pulmonary fungal infections, aspergillosis, and in particular invasive pulmonary aspergillosis (IPA), are becoming the most worrying diseases in immunocompromised patients. This is due to their high incidence and mortality. Indeed, invasive aspergillosis manifests as invasive pulmonary disease accounting for 50/60% of all cases, with a mortality of 50-90% in severely immunocompromised patients. Triazoles act by inhibiting 14-α demethylase, a fungal cytochrome P450 enzyme implicated in the synthesis of ergosterol, an essential constituent of fungal cell walls. Moreover, they interact with the same cytochrome present in large quantities in the human liver, inducing possible drug-drug interactions in IPA patients. Consequently, interactions resulting from inhibitors, inductors, or substrates of cytochromes can modify the plasmatic concentrations of triazoles or other drugs administered concomitantly. To overcome these important issues, pulmonary delivery of triazoles could be an interesting alternative to conventional routes.The aim of this work was to develop triazole-based dry powders for inhalation able to be deposited adequately in the lungs, with a release of drug and a lung retention that can optimize its pharmacological action. This work focused on two active pharmaceutical ingredients (API): itraconazole (ITZ), for which improved solubility was needed, and voriconazole (VCZ), for which slow release was required.Concerning ITZ, solid dispersions for inhalation (SDIs) comprising ITZ and mannitol were previously developed in our laboratory. The selected SDI showed interesting results in terms of improved dissolution and lung retention in vivo in mice during a pharmacokinetic study. Therefore, this SDI was tested in a murine preclinical model of IPA and showed promising results in terms of prophylaxis efficacy. One aim of this work was to continue the pharmaceutical development of this promising SDI by making a scaling-up study. These methods were intended to improve the SDI’s ecological footprint and productivity by increasing the production yield and decreasing the amount of solvents and time used in its manufacture. During the first step of this study, the obtained SDI showed interesting results obtaining similar powder characteristics (i.e. amorphous content, aerodynamic performance, and dissolution profiles) from concentrated solutions using a laboratory-scale spray-dryer B-290 (Büchi, Switzerland) before using a pilot-scale spray-dryer (GEA Niro, Denmark). Then, the upscaling was performed on the pilot spray-dryer allowing the production of SDIs with increased productivity (yield and process duration). These SDIs had similar powder characteristics than the optimized lab-scale SDIs. During the second part of this work we developed VCZ based dry powder for inhalation. The aim was to slow down the release of this highly permeable and very slightly soluble API and to prolong its lung residence. To this end, various lipidic excipients were chosen. The selection took into account the potential good pulmonary tolerance of the lipids and their hydrophobicity to evaluate their ability to slow down the VCZ release (FPFs 20-25%, slowed release up to 24h, burst effect of ± 58% of VCZ dissolved within 30min). Immediate-release SDIs were also developed to have a comparator reference for the pharmacokinetic and efficacy studies (FPFs of 40%).Then, a pharmacokinetic study in mice was performed following the pulmonary administration of one immediate-release and two sustained-release SDIs (with or without PEG excipient). With an 80-fold higher pulmonary exposure over 24 hours, the slow-release SDIs presented a real interest compared to the immediate-release SDI. Moreover, in accordance with these results, VCZ plasma exposure following the administration of the SDI with PL90-H was more than 1.5-fold higher than its pulmonary exposure (AUC0-24 of 8.70 µg.h/g in the lungs and 14.70 µg.h/mL in the plasma). The slow-release formulations presented plasma exposures at least 15 times lower than their pulmonary exposures (AUC0-24 in lung of 741.40 and 686.85 µg.h/g vs plasmatic AUC0-24 of 37.44 and 42.81 µg.h.mL, respectively with and without PEG excipient). Moreover, the presence of PEG excipient did not influence the residence time and the exposure of the VCZ within the lungs. Finally, the sustained-release SDIs administration by inhalation led to VCZ lung and plasma concentrations higher than the minimal inhibitory concentration (MIC) of VCZ against Aspergillus fumigatus (1 μg/mL) over 24 h. Finally, a murine model of IPA was developed in our lab. The immunosuppression model was fixed and performed by the intraperitoneal (IP) injection of corticosteroids to induce a neutropenia state. Then, different doses of spores (from 1.10^4 to 5.10^6 spores) were inoculated to the neutropenic mice via an endotracheal instillation and the survival rate of each group was observed. Unfortunately, the survival rate resulting from the different infections were not reproducible. Therefore, these models were not suitable to conduct the efficacy study. This underlined the link between the immunosuppressive model and the infection. Indeed, the IPA murine model should be developed according to the immune state of the animal, the Aspergillus conidia species and its concentration to be used. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

<p>Understanding the drying of droplets is of interest for processes such as spray drying, where particulate materials are produced by evaporating moisture. Even though spray-drying is a widely used method, there are still challenges, such as undesired agglomeration or controlling the morphology and size of the final dried product. This dissertation develops a physics based model that is used to examine the droplet dynamics and drying kinetics at large and small scales.  In addition, the model simulates the internal motion of insoluble particles and  is used to better understand particle formation during spray drying type processes.</p> <p><br></p> <p>The first part of this work examines the effect of droplet-droplet collisions on evaporation and the size distribution at a large scale. Droplet collision dynamics are implemented into an Eulerian-Lagrangian framework, where droplets are tracked in the Lagrangian frame, and the background gas is modeled as a continuum. The modeling framework includes fully coupled interphase heat and momentum transfer between the droplet and gas phases. Binary collision of droplets could result in coalescence, reduction in surface area, or separation of droplets, resulting in the generation of satellite droplets and an increase in total surface area. By capturing the change in size distribution due to the collision of particles, our results show a linear relationship between the Weber number and the evaporation rate at low droplet number densities. Further, it is shown that droplet number density is a critical factor influencing the evaporation rate. At high droplet number densities, the relationship between the evaporation rate and the Weber number becomes non-linear, and at extremely high droplet number densities, the evaporation rate decreases even at high Weber numbers.</p> <p><br></p> <p>In the next part of this dissertation, the drying of a single droplet containing insoluble solid particles is investigated. Using a volume-of-fluid framework coupled with the Lagrangian phase, we study the particle transport within a droplet, and how it is affected by airflow, phase properties (e.g., viscosity and density of each phase), surface tension, and evaporation. Unlike the traditional one-dimensional modeling approach, our multi-dimensional model can capture the generation of internal flow patterns due to shear flow and the accumulation of solid particles on the surface of the drying droplet. Our results show that the surface tension effect is more pronounced at larger droplet diameters and low airflow velocities. Our approach also provides a quantitative method for modeling crust growth and formation. </p> <p>Our results show that increasing solids mass fraction, and decreasing particle diameter, slow down the internal transport of solid particles, leading to a more quick accumulation near the surface of the droplet. Further, despite the droplet undergoing a constant-rate drying stage, the accumulation of solids near the surface is non-linear. In addition, the inclusion of solids within the droplet drastically reshapes the formation of internal vortices compared to the uncoupled case, which determines solids distribution.</p>