Esta tese de doutorado trata do desenvolvimento inédito de formas farmacêuticas sólidas contendo nanocápsulas de núcleo lipídico, facilmente redispersíveis em água, empregando a secagem por aspersão ou granulação em leito fluidizado. A estratégia visa superar limitações tecnológicas associadas às suspensões de nanocápsulas poliméricas, pela sua natureza coloidal, e avançar na fronteira do conhecimento, buscando o desenvolvimento de formulações inovadoras para a administração oral de fármacos. Foram produzidos pós e grânulos contendo nanocápsulas de núcleo lipídico (LNC), empregando a secagem por aspersão e granulação em leito fluidizado, respectivamente. A influência do número de partículas das suspensões de nanocápsulas nas propriedades de redispersão dos pós produzidos pela secagem por aspersão foi investigada. Uma mistura de maltodextrina e L-leucina (90:10 m/m) foi utilizada como adjuvante de secagem. A formulação que obteve os melhores perfis de redispersão consistiu de uma mistura da suspensão de nanocápsulas de núcleo lipídico e de uma solução contendo maltodextrina/L-leucina (10% m/v) em uma proporção 1:1 v/v. Após a redispersão dos pós produzidos em água, 75% do número inicial de partículas de nanocápsulas foi recuperado. Análises de área superficial, microscopia eletrônica de varredura e microscopia confocal Raman permitiram compreender as diferenças na organização estrutural destes pós. Estes dados, em conjunto com análises de diâmetro médio de partículas, obtidos por difratometria de laser, confirmaram a influência do número inicial de partículas das suspensões de nanocápsulas na qualidade de sua redispersão, a partir de formulações sólidas obtidas pela secagem por aspersão. Para compreender as influências dos processos de secagem e redispersão da formulação proposta no perfil de liberação in vitro e na atividade biológica de fármacos associados ao sistema, novos pós foram preparados, substituindo-se a suspensão de nanocápsulas sem fármaco (LNC) por nanocápsulas contendo uma substância ativa modelo (curcumina) (LNC-C 1 mg mL-1). A formulação seca demonstrou adequada redispersão em água e o perfil de liberação in vitro manteve-se semelhante ao da suspensão original (LNC-C), seguindo um modelo cinético de ordem zero. A atividade da curcumina nanoencapsulada foi avaliada empregando um modelo de inflamação induzida por LPS em cultura organotípica de cultura de hipocampo cerebral de ratos. Não houve alterações nas concentrações de biomarcadores pró-inflamatórios (TNF-α e IL-1β) liberados nos meios de cultura, comparando-se as LNC-C em suspensão ou a redispersão dos pós secos. Portanto, a produção de pós facilmente redispersíveis não implica em alterações no controle da liberação in vitro e na atividade biológica da substância ativa nanoencapsulada. Na última etapa, a obtenção dos grânulos empregando granulador em leito fluidizado foi estudada utilizando maltodextrina, como material de suporte, e suspensões de nanocápsulas de núcleo lipídico estabilizadas com polissorbato 80 (LNC) ou com revestimento catiônico (C-LNC), como líquidos aglutinantes. A influência do revestimento catiônico das nanocápsulas nas características tecnológicas dos grânulos obtidos foi avaliada. Propriedades como o tamanho de partícula, rendimento, teor de umidade, características morfológicas, propriedades de fluxo e perfil de redispersão foram estudados. Os rendimentos do processo de granulação foram próximos a 90%, resultando em grânulos com teor de umidade inferior a 4%. Valores calculados de índice de Carr, fator de Hausner e índice de coesão indicaram que as formulações de grânulos propostas neste estudo apresentam melhores características de fluxo em relação à maltodextrina (matéria-prima). O revestimento catiônico das nanocápsulas melhorou tanto as propriedades de fluxo quanto o perfil de redispersão em água dos grânulos contendo C-LNC, demonstrado a partir das análises de diâmetro médio de partículas por difratometria de laser. Em conclusão, os processos de secagem por aspersão e granulação em leito fluidizado, empregados neste estudo, para a produção de formas farmacêuticas sólidas intermediárias e/ou finais contendo nanocápsulas de núcleo lipídico, mostraram-se alternativas viáveis para a produção de pós e grânulos facilmente redispersíveis em água, com potencial aplicação para administração oral de fármacos nanoencapsulados. / This thesis proposes the development of novel easily redispersible solid dosage forms containing lipid-core nanocapsules, produced by spray drying or fluidized bed granulation. The strategy aims to overcome the technological limitations associated to polymeric nanocapsule suspensions, due to their colloidal nature, aiming the development of innovative oral formulations. Powders and granules containing lipid-core nanocapsules (LNC) were produced by spray-drying and fluidized bed granulation, respectively. The influence of the number of particles of the nanocapsule suspensions on the redispersion properties of the spray-dried powders was investigated. A mixture of maltodextrin and L-leucine (90:10 m/m) was used as a drying adjuvant. The formulation that obtained the best redispersion profiles consisted of a mixture of the lipid-core nanocapsule suspension and a solution containing maltodextrin/L-leucine (10% w/v) in a 1:1 v/v ratio. After the aqueous redispersion, 75% of the initial number of particles in the nanocapsules suspension was recovered. Analysis of surface area, by scanning electron microscopy and by Raman confocal microscopy allowed understanding the differences in the structural organization of the powders produced. These results along with the mean diameter analysis by laser diffractometry confirmed the influence of the initial number of particles of the nanocapsule suspensions on the redispersion properties of the spray-dried powders. In order to understand the influence of the drying and redispersion processes on the in vitro release profile and the biological activity of substances associated to this system, new powder formulations were prepared by replacing the unloaded suspension of nanocapsules (LNC) by nanocapsules containing an active substance (curcumin) (LNC-C 1 mg mL-1). The spray-dried powder showed good aqueous redispersion profile and its in vitro release profile remained similar to that of the original LNC-C suspension, according to the zero-order kinetic model. The biological activity of nanoencapsulated curcumin was assessed by a model of LPS-induced inflammation in organotypic hippocampal slice cultures. There were no changes in the concentration of pro-inflammatory biomarkers (TNF-α and IL-1β) released in the culture media, comparing the LNC-C as the initial suspension or the aqueous redispersion of their spray-dried powders. The drying process does not imply changes in the control of in vitro release and in the biological activity of the nanoencapsulated active substance. In the last stage, granules were produced using a fluidized bed granulator and maltodextrin, as support material. Lipid-core nanocapsules suspensions stabilized with polysorbate 80 (LNC) or with a cationic coating (C-LNC) were used as binder liquids. The influence of the cationic coating of the nanocapsules on the technological characteristics of the produced granules was evaluated. Properties such as particle size, yield, moisture content, morphological characteristics, flow properties and redispersion profile were also studied. Granulation process yields were close to 90%, resulting in granules with moisture content of less than 4%. Calculated values of Carr index, Hausner ratio and cohesion index indicated that the granule formulations proposed in this study present better flow characteristics in relation to the maltodextrin raw material. The cationic coating of the nanocapsules improved the flow properties and the aqueous redispersion profile of the granules containing C-LNC, as demonstrated by laser diffraction analysis. In conclusion, the spray-drying and fluidized bed granulation processes used in this study are viable alternatives for the production of easily redispersible powders and granules containing lipid-core nanocapsules, showing potential application for oral administration of drug-loaded lipid-core nanocapsules.

Ce mémoire porte sur l'élaboration et la caractérisation d'un matériau composite chitosane/phosphate de calcium destiné à une utilisation dans le domaine de la substitution osseuse. Le procédé d'atomisation-séchage a été choisi pour élaborer ce composite sous forme d'une poudre susceptible d'être transformée en revêtement ou objet 3D. Une étude préliminaire a permis d'appréhender les mécanismes de synthèse du phosphate de calcium, la phase minérale, par atomisation-séchage. Une suspension de particules d'hydroxyapatite stœchiométrique ou d'apatite biomimétique dispersées dans une solution acide mène systématiquement à l'apparition d'une phase amorphe. La proportion de cette phase amorphe dans la poudre atomisée-séchée est dépendante de la taille et de la cristallinité du matériau d'origine. L'atomisation séchage d'une solution acide contenant les ions précurseurs de calcium et phosphate mène à la formation d'une phase principalement amorphe. Cette poudre a pu être décrite à différentes échelles : à une échelle de l'ordre du nanomètre apparaissent des clusters, à une échelle de l'ordre de la centaine de nanomètres des agrégats sphériques de clusters organisés en chapelet tortueux et imbriqués sont identifiés et enfin à une échelle micrométrique des agglomérats de nanoparticules ont été mises en évidence. Le phosphate de calcium ainsi synthétisé possède un rapport molaire Ca/P proche de 1.3. Au-delà de ce rapport dans la solution à atomiser, de l'acétate de calcium (utilisé ici comme précurseur) recristallise dans la poudre. Pour élaborer la poudre composite, le polymère a été solubilisé et ajouté d'abord dans une suspension acide d'hydroxyapatite avant atomisation. Cette première stratégie mène à la formation d'un composite qui présente de fortes inhomogénéités de répartition des phases organiques et minérales. Pour limiter ce problème lié à la distribution de tailles de grains de la phase minérale, une seconde stratégie a été développée. Une solution de polymère contenant des précurseurs de phosphate de calcium a été préparée pour favoriser l'association à l'échelle nanométrique des deux phases. Après atomisation-séchage, un matériau composite présentant une très bonne dispersion de la phase minérale dans la matrice organique est synthétisé. La structuration de la phase minérale est modifiée par la présence du polymère. Cette modification se traduit par une diminution de la fraction volumique des clusters et, à l'échelle supérieure, la phase minérale n'est plus présente sous forme de chapelet mais en particules sphériques isolées. Par ailleurs, une interaction chimique est envisagée en raison des liaisons de type hydrogène, ioniques ou de coordinations possibles entre les deux phases. La présence du polymère inhibe également la formation de l'acétate de calcium cristallin en favorisant la formation d'un sel d'acétate de chitosane. Deux techniques de mises en forme ont été étudiées (MAPLE, pour l'élaboration de revêtements minces et l'impression 3D de pâte pour l'obtention d'objet massif) et ont permis de mettre en avant le potentiel de transformation de la poudre préparée par atomisation séchage. Les études biologiques faites sur le revêtement ont de plus permis de démontrer les propriétés antibactériennes du matériau utilisé. / This thesis deals with the development and characterization of a chitosan/calcium phosphate composite material for use in the field of bone substitution. The spray-drying method was chosen to develop this composite in the form of a powder that could be transformed into a coating or 3D object. A preliminary study made it possible to understand the mechanisms of synthesis of calcium phosphate, the mineral phase, by spray-drying. A suspension of stoichiometric hydroxyapatite particles or biomimetic apatite dispersed in an acidic solution systematically leads to the appearance of an amorphous phase. The proportion of this amorphous phase in the spray-dried powder is dependent on the size and crystallinity of the original material. The spray drying of an acidic solution containing the precursor ions of calcium and phosphate leads to the formation of a mainly amorphous phase. This powder could be described at different scales: on a scale of about one nanometer appear clusters, on a scale of about one hundred nanometers spherical aggregates of clusters organized into tortuous and nested chaplets are identified and finally on a micrometric scale, agglomerates of nanoparticles were highlighted. The calcium phosphate thus synthesized has a molar ratio Ca/P close to 1.3. Beyond this ratio in the solution to be atomized, calcium acetate (used here as a precursor) recrystallizes in the powder. To develop the composite powder, the polymer was solubilized and added first into an acid suspension of hydroxyapatite before atomization. This first strategy leads to the formation of a composite that has strong in homogeneities in the distribution of organic and inorganic phases. To limit this problem related to the grain size distribution of the mineral phase, a second strategy has been developed. A polymer solution containing calcium phosphate precursors has been prepared to promote nanoscale association of the two phases. After spray-drying, a composite material having a very good dispersion of the mineral phase in the organic matrix is synthesized. The structuring of the mineral phase is modified by the presence of the polymer. This modification results in a reduction of the volume fraction of the clusters and, on the larger scale, the mineral phase is no longer present in the form of a string but in isolated spherical particles. Moreover, a chemical interaction is envisaged because of the hydrogen, ionic or possible coordination bonds between the two phases. The presence of the polymer also inhibits the formation of crystalline calcium acetate by promoting the formation of a salt of chitosan acetate. Two shaping techniques were studied (MAPLE, for the elaboration of thin coatings and the 3D printing of dough for obtaining massive objects) and made it possible to highlight the transformation potential of the prepared powder by spray drying. The biological studies made on the coating have also demonstrated the antibacterial properties of the material used.

O interesse pela extração dos compostos bioativos, a partir de fontes naturais, para o emprego na produção de alimentos funcionais tem aumentado, devido, principalmente, à crescente demanda por parte dos consumidores, por produtos mais saudáveis e que possam trazer benefícios à saúde. Dentre as fontes naturais de compostos bioativos, destaca-se o hibisco (Hibiscus sabdariffa L.), que é rico em antocianinas, flavonoides, ácidos fenólicos, carotenoides, dentre outros. Entretanto, quando os compostos bioativos são separados de suas matrizes, estes se tornam altamente instáveis frente a diversos fatores ambientais, necessitando serem protegidos. O recobrimento por microencapsulamento é uma alternativa para retardar a degradação desses compostos. Este estudo teve como objetivo a extração, identificação, quantificação e microencapsulamento por atomização e liofilização dos compostos bioativos dos cálices do hibisco. Primeiramente, foi realizada a extração exaustiva total dos carotenoides e compostos fenólicos por meio de solventes orgânicos, para a identificação e quantificação desses compostos. Também foi estudada a extração de antocianinas e demais compostos fenólicos por meio de solvente aquoso acidificado (ácido cítrico 2 %, p/v). A partir do melhor tratamento de extração, o extrato obtido foi microencapsulado mediante atomização e liofilização, empregando goma arábica (GA), goma guar parcialmente hidrolisada (GGPH) e polidextrose (PD) como agentes encapsulantes, na concentração de 10%. Os carotenoides e compostos fenólicos foram identificados e quantificados por HPLC-DAD-MS/MS (cromatografia líquida de alta eficiência com detecção por arranjo de diodos e espectrometria de massa). Vinte e um carotenoides foram encontrados, dos quais, quinze foram identificados. O total de carotenoides nos cálices de hibisco foi de 641,38 ± 23,61 μg/100 g massa fresca, sendo a all-trans-luteína e o all-trans--caroteno os compostos majoritários, representando 49 e 23%, respectivamente. Para os compostos fenólicos, foram encontrados vinte compostos, dos quais, catorze foram identificados. As antocianinas foram os compostos majoritários nos cálices de hibisco, sendo que a delfinidina 3-sambubiosídeo e cianidina 3-sambubiosídeo representaram 41 e 13% do total de compostos fenólicos, respectivamente. Dentre os ácidos fenólicos, os componentes majoritários foram o ácido 3-cafeoilquínico e ácido 5-cafeoilquínico, representando 15 e 13% do total de compostos fenólicos, respectivamente. Para a extração aquosa acidificada, foi utilizado um planejamento experimental fatorial fracionado (24-1), com quatro fatores: concentração de enzima, temperatura, velocidade de agitação e tempo de extração. A partir da ANOVA, os efeitos principais e de interação foram avaliados, tendo como respostas Chroma, antocianinas monoméricas totais (TMA), capacidade redutora, ABTS e compostos fenólicos. A partir dos resultados, o melhor tratamento foi: 55 °C, 50 μL de enzima/1000 g extrato, 400 rpm e 4 horas de extração, obtendo-se nessa condição de extração 3,82 mg/g extrato em base seca para TMA e 17,59 mg/g de extrato em base seca para compostos fenólicos totais, que resultou em capacidade antioxidante de 7,72 μmol Eq. Trolox/g de extrato em base seca, avaliado por ABTS e de 3,96 mg GAE/g de de extrato em base seca, avaliado pela capacidade redutora. Este extrato foi empregado no estudo de encapsulamento, por atomização (140 ºC) e liofilização (-68 ºC por 24 horas), utilizando GA, GGPH e PD como encapsulantes. Observou-se que o melhor tratamento foi por liofilização empregando GA como encapsulante, resultando em 2,83 mg/g amostra em base seca para TMA, capacidade antioxidante de 2,98 mg GAE/g amostra em base seca e 5.67 μmol Eq. Trolox/g amostra em base seca, avaliados por capacidade redutora e ABTS, respectivamente. Entretanto, quando foram avaliadas as propriedades físicas e morfológicas dos pós, as amostras elaboradas por atomização e usando GA e GGPH apresentaram os melhores desempenhos, onde os valores de solubilidade, higroscopicidade e umidade foram de 95,8 e 95,2%, 31,3 e 28,9%, 1,9 e 2,4%, respectivamente. Para a temperatura de transição vítrea (Tg), os tratamentos que utilizaram GA e GGPH nos dois métodos de encapsulamento, tiveram os maiores valores de Tg, variando de 10,9 a 17,4 ºC. Já para os tratamentos que utilizaram a PD como material de parede, os valores foram de (0,7 °C), tanto na atomização como na liofilização. Na microscopia também foi observado um melhor desempenho nas micropartículas atomizadas usando GA e GGPH, as quais mostraram partículas mais esféricas e sem tendência de atração e aderência entre si. Em relação ao diâmetro médio de partícula (D[4, 3]), os tratamentos liofilizados tiveram partículas maiores que os atomizados, variando de 101,7 a 143,1 μm para os liofilizados, e de 5,4 a 7,3 μm para os atomizados. Quanto ao span, o qual avalia distribuição de tamanho de partícula, variou de 1,90 a 2,00 para as amostras atomizadas e de 3,06 a 3,19 para as amostras liofilizadas, indicando que houve uma boa uniformidade na distribuição de tamanho de partícula. Conclui-se que o hibisco é uma matriz com ampla composição de compostos bioativos e tem potencial para aplicação em alimentos. / The interest in the extraction of bioactive compounds from natural sources, for use in the production of functional foods has increased, mainly due to the growing demand by consumers for healthier products and can bring health benefits. Among the natural sources of bioactive compounds, stands out the hibiscus (Hibiscus sabdariffa L.), which is rich in anthocyanins, flavonoids, phenolic acids, carotenoids, among others. However, when the bioactive compounds are separated from their matrix, they become highly unstable against various environmental factors and need to be protected. The coating by microencapsulation is an alternative to slow the degradation of these compounds. This study aimed at the extraction, identification, quantification and microencapsulation by spray drying and freeze drying of bioactive compounds of hibiscus calyces. Firstly, a thorough exhaustive extraction of carotenoids and phenolic compounds by organic solvents was performed for identification and quantification of these compounds. The extraction of anthocyanins was also studied along with other phenolic compounds by an aqueous solvent acidified (2% citric acid, w/v). From the best treatment for extraction, the extract obtained was microencapsulated by spray drying and freeze drying using Arabic gum (GA), partially hydrolyzed guar gum (PHGG) and polydextrose (PD) as encapsulating agents in a concentration of 10%. Carotenoids and phenolic compounds were identified and quantified by HPLC-DAD-MS/MS (high-performance liquid chromatography with diode array detection and mass spectrometry). Twenty-one carotenoids were found, of which fifteen were identified. The total carotenoids in hibiscus calyces was 641.38 ± 23.61 mg/100 g fresh weight, with the all-trans-lutein and all-trans-β-carotene the major compounds, representing 49 and 23%, respectively. Regarding the phenolic compounds it was found twenty of those, of which fourteen have been identified. Anthocyanins were the main components in the hibiscus calyces, and delphinidin and cyanidin 3-sambubioside 3-sambubioside represented 41 and 13% of total phenolic compounds, respectively. Among the phenolic acids, the major components were the 3-caffeoylquinic acid and 5-caffeoylquinic acid, representing 15 and 13% of total phenolic compounds, respectively. For acidified aqueous extraction, we used a fractional factorial design (24-1) with four factors: enzyme concentration, temperature, stirring speed and extraction time. From the ANOVA, the main and interaction effects were assessed as answers: Chroma, total anthocyanins monomeric (TMA), reducing capacity, ABTS and phenolic compounds. From the results, the best treatment was with 55 °C, 50 μL of enzyme/1000 g extract, 400 rpm and 4 hours of extraction, it was obtained in this extraction condition 3.82 mg/g extract on a dry basis for TMA and 17.59 mg/g extract on a dry basis for phenolic compounds, which resulted in antioxidant capacity of 7.72 μmol Eq. Trolox/g extract on a dry basis, evaluated by ABTS and 3.96 mg GAE/g extract on a dry basis, assessed by reducing capacity. This extract was used for the encapsulation study, by spray drying (140 °C) and freeze drying (-68 ° C for 24 hours) using GA, PHGG, and PD as encapsulants. It was observed that the best treatment is by freeze drying using GA as encapsulant, resulting in 2.83 mg/g sample on dry basis for TMA, antioxidant capacity of 2.98 mg GAE/g sample on dry basis and 5.67 μmol Eq. Trolox/g sample on dry basis, evaluated by reducing capacity and ABTS, respectively. However, when we evaluated the physical and morphological properties of powders, samples prepared by spray drying and using GA and PHGG showed the best performance, and the values for solubility, hygroscopicity and moisture were 95.8 and 95.2%, 31.3 and 28.9%, 1.9 and 2.4%, respectively. For the glass transition temperature (Tg), treatments with GA and PHGG on both encapsulation methods had high Tg values ranging from 10.9 to 17.4 °C. As for treatments of PD as wall material, the values were (0.7 °C), both the spray drying as in freeze drying. In microscopy was also observed improved performance in spray-dried microparticles using GA and PHGG, which showed more spherical particles and with no tendency to attract and adhere to each other. Regarding the average particle diameter (D [4, 3]), the freeze-dried treatments had higher spray-dried particles ranging from 101.7 to 143.1 μm for freeze-dried, and 5.4 to 7.3 μm for spray-dried. As the span, which assesses particle size distribution ranged from 1.90 to 2.00 for spray-dried samples and 3.06 to 3.19 for the freeze-dried samples, indicating that there was a good uniformity in the size in the distribution of the size of the particle. It follows that hibiscus is a matrix with broad composition and bioactive compounds have potential for application in foods.

A busca de novas soluções em produtos e processos guia o desenvolvimento da indústria de alimentos. Os produtos desidratados apresentam vantagens em relação à facilidade de manuseio, custos de transporte e armazenagem e, em geral, maior durabilidade quando comparados às suas formas hidratadas. O iogurte é muito bem aceito pela sociedade brasileira e, se desidratado, pode vir a ser utilizado como ingrediente em diversos alimentos industrializados, propiciando o desenvolvimento de novos produtos. Este trabalho procura estabelecer condições ótimas para a secagem de iogurte natural por atomização (spray drying) em equipamento com disco rotativo em escala piloto. A caracterização do sistema e de suas respostas foi feita com auxílio de projetos fatoriais e metodologia de superfícies de respostas. Por meio de otimização multiobjetivo foi determinada a fronteira de Pareto de soluções ótimas para um modelo ponderado com funções compostas de atributos de qualidade do produto cor, temperatura do ar de saída da câmara de secagem, span e umidade; e de índices de desempenho do processo, com base na quantidade de material seco quantidade de produto obtido, material retido na parede da câmara de secagem e perdas no equipamento. Em virtude da natureza do iogurte houve depósito de produto na parede da câmara, o que motivou a pesquisa de aditivos para auxiliar a secagem. Foi estudada a influência de maltodextrinas DE 5, DE 10 e EMPCAP -, goma acácia, leite em pó desnatado e sílica pirogênica. A sílica pirogênica interferiu na formação de pontes sólidas entre as partículas, reduzindo a quantidade de material depositado na parede e aumentando a recuperação de produto. Para condições operacionais de velocidade de rotação do disco de 26000 rpm, temperatura do ar de entrada na câmara de secagem de 160 °C e depressão na câmara de secagem de 140 mmH2O, as condições ótimas de processo foram encontradas nas seguintes vazões de alimentação de iogurte natural batido adicionado de 3% (m/m) de sílica pirogênica: para o ótimo de qualidade produto, 10,3 kg/h; para o ótimo de desempenho de processo, 3,5 kg/h; e para a condição de pesos iguais entre produto e processo, 6,2 kg/h. A comparação dos resultados previstos pela otimização e os verificados experimentalmente mostrou que o modelo proposto foi adequado. / The search for new solutions in products and processes guide the development of the food industry. Dried products have advantages for ease of handling, transportation and storage costs, and in general, better durability when compared to their hydrated forms. Brazilian society accepts Yoghurt very well and, if dehydrated, could be used as an ingredient in many processed foods, promoting the development of new products. The aim of this paper is to establish optimal conditions for spray drying yoghurt on a wheel pilot plant atomizer. The system characteristics and outputs were established through factorial design and surface response methodology. Multi-objective optimization produced a Paretos optimal solution set for a weighted model built of composite functions. One composite function was consisted of product quality attributes: color, drying chamber output air temperature, span and moisture. The other composite function was made by drying process performance indexes: dry mass recovery, dry mass adhered on the wall and dry mass loss in equipment. The stickiness behavior of yoghurt led the search for drying aid additives. The influence of maltodextrins DE 5, DE 10 and EMCAP, acacia gum, skimmed milk powder and fumed silica was studied. Fumed silica has a negative influence in solid bridges formation between particles, thereby reducing the amount of dry mass adhered on the wall and increasing product recovery. For operating conditions of rotating speed of 26000 rpm, inlet air temperature of 160 °C and 140 mmH2O depression in drying chamber and a feed rate of beaten yoghurt with 3% (w/w) fumed silica concentration, optimal process conditions were found: product quality optimum, 10.3 kg/h; process performance optimum, 3.5 kg/h, and equal weights for product and process optimum, 6.2 kg/h. Experimental verification of the proposed optimization model suggests its adequacy.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Pesquisas recentes apontam a utilizaÃÃo de sucos de frutas como excelente meio para veicular micro-organismos probiÃticos. Diante disso, o objetivo desse trabalho foi desenvolver um novo alimento probiÃtico de origem nÃo lÃctea, a partir da desidrataÃÃo, por spray dryer, do suco de abacaxi contendo Lactobacillus casei NRRL B-442. Primeiramente, foi realizado um tratamento tÃrmico no suco de abacaxi (90 ÂC /1minuto) com o objetivo de inativar as proteases presentes no mesmo e avaliar a influÃncia da inativaÃÃo dessa enzima na sobrevivÃncia do micro-organismo. Posteriormente, foi avaliado o uso de trÃs temperaturas (150, 120 e 100 ÂC) para a desidrataÃÃo do suco, a fim de definir uma temperatura adequada com base na sobrevivÃncia do micro-organismo apÃs o processo de desidrataÃÃo. Outros parÃmetros tambÃm foram estudados, tais como: o efeito da adiÃÃo de diferentes materiais (gelatina, goma arÃbica, maltodextrina), os quais foram empregados como agentes protetores do micro-organismo, bem como a concentraÃÃo de cada agente utilizada. A viabilidade do L. casei antes e apÃs a secagem, os nÃveis de rendimento e reidrataÃÃo do pà e a cor do suco reconstituÃdo tambÃm foram avaliados. Com base nos resultados obtidos podemos concluir que o uso de temperaturas mais baixas (100ÂC) e a aplicaÃÃo de tratamento tÃrmico no suco favoreceram a sobrevivÃncia do L. casei apÃs desidrataÃÃo do suco. O emprego de 10% de gelatina e 5% de goma arÃbica, como agente de proteÃÃo, garantiu excelentes nÃveis de sobrevivÃncia do micro-organismo apÃs a secagem mostrando, dessa forma, que à possÃvel formular um novo alimento probiÃtico em pà sem as limitaÃÃes dos produtos lÃcteos. / Recent researches show the potential use of fruit juices as an excellent way to carry probiotic microorganisms. Thus, the aim of the following study was to develop a new non-dairy probiotic food from of pineapple juice containing Lactobacillus casei NRRL B-442 dehydrated by spray-drying process. Firstly, the pineapple juice underwent a heat treatment (90  C / 1 minute) in order to inactivate the proteases present in the juice and evaluate the influence of enzyme inactivation on the microorganism survival. Subsequently, the employment of three temperatures (150, 120 and 100  C) on the juice dehydration was appraised, with the purpose of defining an appropriate temperature based on the microorganism survival, after the dehydration process. Other parameters were also studied, such as: the effect of addition of different materials (gelatin, gum arabic, maltodextrin), which were used as protective agents for the microorganism, as well as the concentration of each tested adjuvant. Viability of L. casei (before and after the drying process), powder yield and rehydration levels and the color of the reconstituted juice were also assessed. Based on the attained results, it can be concluded that the utilization of lower temperatures (100  C) and the appliance of heat treatment in the juice favored the survival of L. casei after dehydration. Excellent levels of microorganism survival after the drying process were achieved by using 10% gelatin and 5% gum arabic as protective agents, thus showing a promising possibility of formulating a new powder probiotic food without the restrictions inherent in dairy products.

This thesis project studied microcrystalline cellulose II (CII), a polymorphic form of cellulose, which has lower mechanical properties, less plastic deformation, higher elastic recovery and faster disintegration properties than microcrystalline cellulose I (CI). Also, the effects of processing and silicification on CII materials were investigated. Particle modification through spray drying, wet granulation and spheronization was employed to improve CII performance. Spray-drying (SDCII) and wet granulation (WGCII) produced materials with no difference in mechanical or disintegration properties from unprocessed CII, but did show an increase in density and particle flow. Conversely, spheronization (SPCII) showed the poorest mechanical properties compared to CII. Further, SDCII showed better dilution potential than CII. Thus the advantages of SDCII were apparent when it was mixed with a poorly compressible drug (acetaminophen) because fibrous CII was converted to spheroidal particles through spray drying. The rapid disintegration of SDCII and CII compacts was due to water wicking through capillaries followed by compact bursting. Compacts of ibuprofen mixed with SDCII and Avicel® PH-102 had comparable disintegration rates and release profiles compared to ibuprofen formulated with commercial disintegrants and Avicel® PH-102, especially at levels 10% w/w. Adding fumed silica into CII particles through spray drying, wet granulation (WGCII) and spheronization (SPCII) at 2-20% w/w was also studied. Silicification increased physical properties such as true density, Hausner ratio, porosity, ejection force and specific surface area of SDCII and WGCII. Other properties such as bulk and tap densities were reduced due to the amorphous and light character of fumed silica. Spheronized CII showed no change in these properties with silicification. Silicification diminished lubricant sensitivity with magnesium stearate due to the competition of SiO2 with magnesium stearate to coat CII particles. Silicification also decreased the affinity of CII for water only at the 20% w/w level due to the few silanol groups available for water interaction compared to surface hydroxyl groups on CII alone. Particle size modification of CII was process-dependent rather than silicification-dependent. Additionally, silicification decreased the apparent plasticity and elastic recovery of SDCII and WGCII when compacted. The former effect along with increased powder porosity increased surface area and compressibility of SDCII and WGCII. Compact tensile strength of silicified CII materials was in the order: spray-dried > wet granulated > spheronized. This order was due to the combined effect of particle morphology and how fumed silica was incorporated and distributed within CII particles. Silicification did not affect the rapid disintegration properties of CII. Thus, diphenhydramine HCl and griseofulvin tablets prepared with silicified CII had faster disintegration and release than those prepared with commercial silicified CI (Prosolv®). Moreover, CII beads containing diphenhydramine HCl or griseofulvin had faster release profiles compared to beads prepared with Prosolv® SMCC 50 or Avicel® PH-101. This behavior showed that rapid disintegration is an intrinsic property of CII. Compact tensile strength decreased more for unsilicified CI and CII compacts stored at 75% RH, while silicified CI and CII compacts lost less tensile strength under the same conditions. Reprocessed CI materials containing acetaminophen (1:1mixtures) lost 35-72% of their original strength compared to silicified CII materials (15-25% loss) indicating more particle interaction upon recompression. .

In this thesis investigations are carried out on two research topics in context to spray drying. The first research topic is the production of dried particles having uniform characteristics. The second research topic is the development of new applications of the reaction engineering approach which, in recent times, has emerged as an effective tool to formulate drying kinetics models. The reaction engineering approach is also implemented to simulate the drying of monodisperse droplets corresponding to the experimental work in the first research topic. Manufacturing micron- and nano-sized particles having uniform characteristics has recently become a popular research area due to the unique functionalities of these kinds of particles in biomedical, drug delivery, functional foods, nutraceuticals, cosmetics and other valuable applications. Spray drying has been a common and economical route to produce dried particles. A typical characteristic of spray dried products is the existence of a significant variation in particle properties such as size and morphology. One possible idea to restrict this product non-uniformity is to achieve a good control over the droplet’s behaviour and characteristics inside the drying chamber. The current thesis has investigated an innovative spray drying technique, i.e. a single stream drying approach in order to restrict product non-uniformity. In this drying approach, identical sized droplets having vertical trajectories are dried under controlled gas flow conditions. The piezoelectricity-driven monodisperse droplet generator is used as the atomizer to disperse liquid droplets. A prototype single stream dryer was assembled based on the single stream drying approach using various components designed in the laboratory and several parts purchased from the market. Experiments were carried out using aqueous lactose solutions as a model system in order to check the practicability of manufacturing uniform-sized spherical particles. Preliminary results were found to be positive and reported in this thesis. Mathematical models on the drying of monodisperse droplets were developed in order to predict important droplet and gas parameter profiles during single stream drying. These models serve as a platform for design, optimization and scale-up purposes. Several important advantages and drawbacks of single stream drying are also reported. Problems encountered during the experimental work and future recommendations are presented in detail so that a more robust and effective drying research tool can be developed in future. Recently the reaction engineering approach (REA) has emerged as a simple and reliable technique to characterize the drying of various food and dairy materials. In this thesis two new applications of the REA are described for the first time in context to convective drying of aqueous droplets. The REA is used in this study to formulate the drying kinetics model for the drying of aqueous sucrose and maltodextrin (DE6) droplets. The effect of initial moisture content was explicitly demonstrated. The development of a new ‘composite’ REA which aimed to model the drying of aqueous droplets containing multiple solutes has been described. The composite REA was found to be suitable to characterize the drying behaviour of aqueous sucrose-maltodextrin mixtures of different proportions. The second new application of the REA is the development of a procedure to estimate surface properties of aqueous droplets during drying. In literature various droplet characteristics such as surface moisture contents were normally estimated using the diffusion-based drying kinetics model or the receding interface model. Surface moisture content and surface glass transition temperature profiles were evaluated here using a lumped-parameter model (REA) during the drying of aqueous sucrose, maltodextrin (DE6) and their mixtures. The same experimental data used for the development of the composite REA were used to yield predictions. The procedure was found to be useful in estimating surface moisture contents and understanding the stickiness behaviour of sugar droplets during drying. During the formulation of the REA-based drying kinetics model in this thesis, the assumption of uniform temperature within droplets was used. In most studies published in literature the uniform temperature assumption was justified by calculating the heat-transfer Biot numbers at the beginning and end of drying. However, the conventional Biot number concept does not take into account the evaporation effect and therefore would not be suitable to drying scenarios. In this thesis, a new approximation procedure is developed to estimate surface-centre temperature differences within materials following the entire drying process. This new procedure was helpful to check the extent of temperature non-uniformity within skim milk droplets under isothermal laboratory conditions as well as industrial spray drying conditions. Both conventional and drying-based Biot numbers are calculated and compared. Predictions showed that temperature gradients within the droplets were negligible during the drying of suspended droplets under laboratory drying conditions (slow drying), whilst the gradients were small and existed only for a short drying period for small droplets under industrial spray drying conditions (fast drying). Furthermore, it was observed that the maximum temperature gradient within the droplets did not exist at the starting or end points of the drying process, and therefore the estimation of Biot numbers at the starting and end point does not reflect temperature non-uniformity under drying conditions. This is a significant theoretical development in the area.

Novel intervention strategies such as food grade antimicrobials are used to enhance food safety. Nisin is a widely used naturally occurring antimicrobial effective against many pathogenic and spoilage microorganisms. However, its antimicrobial efficacy in food matrices is much reduced because of interactions with food components. Novel delivery systems may overcome this problem by protecting nisin in capsules and releasing it in a controlled manner. The overall goal of this research was to develop delivery systems of nisin to improve its long-term antimicrobial effectiveness. The first objective was to develop a low-cost method to extract nisin from a commercial preparation containing ~2.5% nisin. The best extraction yield was observed at 6 mg solids/mL 50% v/v ethanol. The nisin extract, after adjusting to 70% v/v ethanol, was dissolved with 2% zein (corn prolamins) and different amounts of Tween 20, glycerol, and thymol (another naturally occurring antimicrobial) for spray drying, a practical encapsulation method. Spray-dried capsules were characterized for release profiles of nisin at different pH conditions. Spray drying inlet temperature was first studied at 75 to 120°C, and the greatest sustained release of nisin was observed for capsules produced at 105°C, which was used in rest of this study. The impacts of Tween 20 and glycerol supplemented in spray-drying formulations were studied next. Addition of either 0.05% Tween 20 or glycerol in the spray-drying solution reduced the burst release of nisin at pH 6.0. Capsules with a higher amount of Tween 20 showed more complete release of nisin at pH 8.0, while glycerol had no apparent impact. The most sustained release of nisin at pH 6.0 was observed for capsules produced with both thymol and glycerol. Various capsules were then studied for their ability to inhibit the growth of Listeria monocytogenes at pH 6.0 during incubation at 30°C. Un-encapsulated nisin and thymol showed inhibition only for 12 h, while capsules with nisin and thymol containing either low or medium level of glycerol inhibited L. monocytogenes for >96 h. Our antimicrobial delivery systems, based on food grade ingredients and practical processes, have potential for practical application to enhance microbial safety and extend the shelf-life of foods.

The aim of this research is to understand the solid state physical properties of inulin in regards to the spray-drying treatments. In this context, inulin powders were produced by pilot spray-drying a commercial inulin dispersion under various feed (Tfeed) and inlet air (Tin) temperatures. More particularly, the amorphous and crystalline properties of the powders were studied by developing different fine characterization tools, such as modulated differential scanning calorimetry or powder X-ray diffraction. When the temperature of the inulin water systems increased, the crystallinity of the powder decreased. To a smaller extent, this tendency is also observed with the increase of the inlet air temperature of the spray drier. For example, an amorphous powder is obtained with a Tfeed of 90°C whatever the Tin (comprised between 120 and 230°C); whereas for a Tfeed of 80°C, a Tin of 230°C is necessary to obtain the same result. Adsorption isotherms were established on four powders covering a large range of crystallinity (crystallinity index from 0 to 92). The Guggenheim Anderson de Boer model was fitted to the experimental data. As the water content of the powders increased, the glass transition of inulin decreased. When the Tg droped below the storage temperature (20°C for example), the powders crystallized and underwent clumping phenomenon. Under these conditions, a continuous hard mass was observed for the amorphous powders; while their semi-crystalline counterparts were agglomerated but friable. To understand these changes, a kinetic study of the physical properties evolution and stability of an amorphous powder as a function of its water content was realized. These results allowed to correlate the Tg water content relationship to the evolution of the powders behaviour, such as stickiness or hardening during storage.

Fish and fish waste can be used to produce various value added by products such as proteins, oil, omega-3 fatty acids, biodiesel, amino acids, peptides, collagen, gelatin and silage, each of which has various applications in the food industry, renewable energy and medicinal purposes. Fish protein contains amino acids and many bioactive peptides . Fish proteins are found in the flesh, head, frames, fin, tail, skin and guts in varying quantities. After removing the flesh, all other parts are considered waste which is not properly utilized. The aim of this study was to evaluate the enzymatic extraction of amino acids from fish protein for use as substrates in the microbial production of jadomycin, an antimicrobial agent and potential anti-cancer drug. In this study, enzymatic extraction of proteins was carried out using Alcalase enzyme at three enzyme concentrations (0.5, 1 or 2%) and four time intervals (1, 2, 3 and 4 h). The fish protein hydrolysate was dried using spray dryer to obtain protein powder. The highest protein yield (76.30% from whole fish and 74.53% from the frame) was obtained using 2.0% enzyme concentration after 4 h of hydrolysis. The enzymatic extraction of amino acids were carried out using the enzymes Alcalase and Neutrase (individually and in combination) and the effect of reaction time (24 and 48 h) on the hydrolysis of proteins was studied. The profiling of amino acids was carried out using gas chromatography. Fourteen amino acids were extracted from fish proteins of which twelve amino acids have been used by researchers for the production of jadomycins. These are: alanine (7.59%), glycine (5.82%), histidine (3.59%), isoleucine (5.30%), leucine (9%), lysine (7.34%) methionine (2.2%), phenylalanine (4.2%), serine (4.3%), threonine (5.40%), tyrosine (3.17%) and valine (7.2%). Tryptophan which is suitable of producing jadomycin was not present in the fish protein. No reports were found in the literature for jadomycin production from glutamic acid. Therefore, glutamic acid (9.85%), and proline (0.98%) which are present in the fish protein should be investigated for possible production of jadomycins.