Dissertations / Theses on the topic 'Spray freeze drying'

Nanozirconia ceramics have great potential to be used in a range of applications from dental implants to petrochemical valves due to their enhanced mechanical properties and superior hydrothermal ageing resistance. Unlike conventional ceramic components that are normally produced in large quantities with low costs using various conventional dry forming or wet forming methods, industry scale processing of nanoceramics has not yet been achieved. Concentration and granulation of nanostructured 3 mol% yttria stabilised zirconia via a spray freeze drying (SFD) technique was investigated to determine whether large scale dry forming of nanoceramics would be possible. Commercial nanosuspension with a primary particle size of 16 nm was concentrated to 55 wt% solids content using an electrosteric dispersant, β-alanine, whilst retaining low viscosities of ~20 mPa s at a 200 s-1 shear rate. The nanosuspensions concentrated using the β-alanine also displayed good ageing resistance and it has been proven that a large scale vacuum assisted rotary evaporator can be used to perform concentration in industry.

Industrial exploitation of ceramic nanopowders is inhibited by their poor flowability and strong tendency to agglomerate. To achieve good flowability and die-filling characteristics, controlled agglomeration is required whilst the strength of the agglomerates is minimised so that they crush into primary particles when die pressed. Yttria stabilised zirconia nanopowders with a primary particle size of ~16 nm were obtained through different drying routes from an aqueous suspension and characterised in terms of flowability and agglomerate strength.

This thesis presents an experimental and computational fluid dynamics (CFD) study of spray-drying, spray-freezing and spray-freeze-drying of whey proteins. The effects of varying feed concentration (20 - 40% w/v) and outlet temperature (600 - 120 degrees Celcius) on whey protein denaturation (determined by DSC) and solubility at pH 4.6 (by Kjeldhal and RP-HPLC methods) have been investigated in a pilot-scale cocurrent spray dryer. The study confirms that low outlet gas temperatures (60 and 80 degrees Celcius) produce the lowest amount of denaturation, with almost complete denaturation observed at 120 degrees Celcius. Slightly more denaturation was found with a 40% feed concentration. A reversed phase HPLC technique has been applied to measure the loss of solubility of a-lactalbumin and P-lactoglobulin. Significantly higher losses in solubility were observed for P-lactoglobulin compared to alactalburnin. Increasing the feed concentratioq at higher outlet temperatures also caused noticeable increases in insolubility. The reversed phase HPLC results were consistent with those obtained from total protein nitrogen content (Kjeldhal) analyses. This comparative study suggests that the protein solubility can also be calculated from RP-HPLC technique. Spray-freeze drying is an alternative approach to spray drying, which is less likely to cause protein denaturation and loss of solubility. Conventional freeze-drying involves high capital and operating costs, due to the low temperatures, high vacuum and very long drying times. One solution to this problem is to reduce the dimensions of the material being dried. This is the basis of the spray-freeze-drying technique, involving atomisation of a liquid to form droplets, freezing the droplets and subliming off the ice at low temperature and atmospheric pressure in a fluidised bed. However, the quantities of gas required for atmospheric freeze-drying are prohibitively expensive. A pilot-scale spray-freeze-drying process was investigated, in which fluidisation was performed at sub-atmospheric pressures, allowing rapid freezedrying (in about one hour) but using much less gas. This was demonstrated using whey protein which yields a product with a highly porous structure, with little loss of protein solubility. This process has potential to produce high-value-added food and pharmaceutical products more quickly and cheaply than is currently possible by commercial vacuum freeze-drying processes. CFD simulations were developed for short and tall form spray-dryers to study the particle velocity, temperature and residence time during drying. These simulation results agreed well with the published experimental data. The tall-form spray dryer model predictions showed that more particles impact on the cylindrical wall position and this may affect the protein denaturation and solubility. This study suggests that a short form dryer with a bottom outlet is more suitable for drying of proteins. Similarly, a CFD simulation for the spray-freezing operation was developed to study the gas flow pattern and particle trajectories and histories. This CFD model also includes the latent heat effects during the phase change. The simulation predictions agreed reasonably well with the experimental results. A comparison of simulations for a solid and a hollow cone spray suggested that the latter yields lower particle temperatures with low particle collection efficiency. A modified chamber geometry was proposed and the simulation showed that the new design could achieve higher particle collection efficiencies.

A Chamomilla recutita L. é uma das plantas medicinais mais cultivadas no Brasil e no mundo. Os extratos da C. recutita são de interesse para as indústrias farmacêuticas e cosméticas, visto que estes apresentam atividades anti-inflamatória, antioxidante e adstringente. A ação terapêutica do extrato pode ser mais pronunciada que a ação terapêutica de um de seus ativos isolados. No entanto, a incorporação de um extrato em uma formulação pode ser difícil devido à baixa estabilidade dos extratos, bem como à possibilidade de gerarem instabilidade das formulações. Microencapsulando o extrato com um carreador é possível aumentar estabilidade do extrato quanto evitar instabilidade na formulação. Além disso, a microencapsulação é capaz de fornecer outras vantagens, como uma liberação controlada. Dois processos foram estudados como alternativas para a microencapsulação do óleo essencial e do extrato hidroalcoólico da C. recutita usando quitosana como carreador: o spray drying e o spray freeze drying. Planejamentos fatorais foram utilizados para determinar os fatores que mais influenciaram no diâmetro médio das micropartículas, eficiência de encapsulação e teor dos marcadores e rendimento do processo. A apigenina e a apigenina-7-glicosídeo foram usadas como marcadores do extrato hidroalcoólico e o óxido de bisabolol A foi usado como marcador do óleo essencial. Os processos de spray drying e spray freeze drying dos dois extratos foram otimizados e as micropartículas resultantes foram caracterizadas com relação ao diâmetro médio, rendimento do processo, teor e eficiência de encapsulação dos marcadores, atividade antioxidante in vitro, densidade, índice de Carr, fator de Hausner, umidade, morfologia, perfil de liberação n vitro e estabilidade. Os resultados mostraram que o processo de spray drying apresentou os melhores resultados para eficiência de encapsulação, com valores de aproximadamente 98%, 95% e 80% para apigenina, apigenina-7-glicosídeo e óxido de bisabolol A, respectivamente. As eficiências de encapsulação obtidas no processo de spray freeze drying foram de aproximadamente 59%, 58% e 38% para os mesmos marcadores, respectivamente. As micropartículas produzidas por spray freeze drying apresentaram formato irregular e poroso, enquanto as produzidas por spray drying apresentaram formato esférico e superfícies mais lisas, sem poros ou fissuras. Ao contrário do que ocorreu com o extrato hidroalcoólico, a perda do marcador do óleo foi elevada no processo de spray drying, com teor final de 35%. Os teores dos marcadores ficaram acima de 80% para o processo de spray freeze drying do óleo e acima de 90% para o extrato hidroalcoólico. As micropartículas produzidas por spray drying do extrato hidroalcoólico e do óleo e por spray freeze drying do extrato hidroalcoólico e do óleo apresentaram diâmetro médio de 5,1 ?m, 5,0 ?m, 31,0 ?m e 96,4 ?m, respectivamente. Ensaios de liberação in vitro mostraram que as micropartículas foram capazes de sustentar a liberação dos respectivos marcadores. Os estudos de permeação in vitro das micropartículas produzidas por spray drying do extrato hidroalcoólico também mostraram que estas foram capazes de sustentar a liberação. A microencapsulação proporcionou em todos os casos um aumento considerável da estabilidade. As micropartículas produzidas por spray drying do extrato hidroalcoólico apresentaram teores de marcadores no mínimo 50% maiores que o extrato puro após 90 dias. O spray freeze drying se mostrou como a melhor alternativa para produção de micropartículas de quitosana contendo o óleo essencial de C. recutita, enquanto o processo de spray drying se mostrou como uma ótima alternativa para microencapsulação do extrato hidroalcoólico da C. recutita.
Chamomilla recutita L. is one of the most cultivated medicinal plants in Brazil and around the world. Its extracts are important to both the pharmaceutical and cosmetics industries due to its therapeutic applications, such as an anti-inflammatory, antioxidant, and astringent. The therapeutic effects of an extract may be more pronounced than those of an isolated active compound. However, the incorporation of an extract in a formulation is difficult due to the low stability of extracts and the potential instabilities they may cause in formulations. Microencapsulating an extract in a carrier is a potential way of increasing the stability of an extract and avoiding instabilities in a formulation. Compound microencapsulation also brings other advantages, such as controlled release rates. Two processes were studied as alternatives to microencapsulating C. recutita essential oil and C. recutita hydroalcoholic extract using chitosan as a carrier: spray drying and spray freeze drying. Factorial designs were used to determine which process factors most influence the mean diameter, encapsulation efficiency and content of the chemical markers, and process yield. Apigenin and apigenin-7-glucoside were used as chemical markers for the hydroalcoholic extract and bisabolol oxide A was used as the chemical marker for the essential oil. The spray drying and spray freeze drying processes for both the oil and hydroalcoholic extract were optimized and the resulting microparticles were further characterized to determine mean diameter, process yield, marker encapsulation efficiency and content, in vitro antioxidant activity, density, Carr index, Hausner factor, water content, morphology, in vitro release profiles and stability. The results showed spray drying had the best encapsulation efficiency results, with about 98%, 95% e 80% of the apigenin, apigenin-7-glucoside and bisabolol oxide A content, respectively, inside the microparticles. The encapsulation efficiencies obtained in the spray freeze drying process were about 59%, 58% e 38% for the same chemical markers, respectively. Microparticles produced by spray freeze drying were irregular and porous, whereas microparticles produced by spray drying were spherical and fairly smooth, without porous or cracks. Contrary to what happened with the hydroalcoholic extract, oil marker content was low for spray dried microparticles, with final content at 35%. Chemical markers contents were above 80% for the oil and above 90% for the hydroalcoholic extract in spray freeze dried microparticles. Spray dried microparticles containing extract and oil and spray freeze dried microparticles containing extract and oil had mean diameter of 5.1 ?m, 5.0 ?m, 31.0 ?m and 96.4 ?m, respectively. In vitro release profiles showed all microparticles were able to sustain their respective marker release rates. In vitro permeation studies of spray dried microparticles containing hydroalcooholic extract also showed sustained release rates for the corresponding markers. Microencapsulation also provided considerable increase in C. recutita hydroalcoholic extract stability and C. recutita essential oil stability. After 90 days spray dried microparticles containing hydroalcoholic extract presented marker content 50% higher than the pure hydroalcoholic extract. Spray freeze drying was the best alternative to produce chitosan microparticles containing C. recutita essential oil, while spray drying was shown to be an excellent way to microencapsulate C. recutita hydroalcoholic extract in chitosan.

Per limitare gli effetti tossici delle Ag-NPs, si è pensato che esse possano essere utilizzate in forma di microincapsulati, in quanto le microcapsule possono avere una certa velocità di rilascio sotto specifiche condizioni. Incapsulando quindi le Ag-NPs, posso ottenere un rilascio controllato di esse, in modo da ottenere una concentrazione di esse utile allo scopo per cui vengono impiegate, evitando un sovradosaggio che non porterebbe alcun beneficio ma solo a una maggior probabilità di causare effetti tossici.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico
The objective of this research was to obtain powder from the pulp of integral acerola two drying methods (spray-dryer and freeze drying), and the determination of physical and chemical stability and hygroscopic and morphological characteristics. Acerola pulps were acquired in the trade of Fortaleza. The pulp was characterized and post as the physicochemical, colorimetric and morphological parameters. The study of the stability of the powders was carried out in three distinct packaging for a period of 90 days. The adsorption isotherms were also determined. The results indicated optimal conditions for drying spray-dryer using drying temperature of 154 ÂC and the pulp concentration maltodextrin 17,1%, while in the lyophilizer, 19,1% maltodextrin with lyophilization time of 24 hours. All physico-chemical parameters evaluated in the whole pulp undergo change after drying. The drying spray-dryer powder generated with lower humidity, and lyophilization produced a more hygroscopic powder, with a greater degree of caking, and better color preservation, the pH being a parameter of small variation. The study of the stability of acerola pulp powder obtained by different drying methods allowed us to observe increased humidity and coordinate a* b* and decreased ascorbic acid and brightness. The use of laminated packaging laminate vacuum was effective to maintain moisture and hygroscopic powder, with less loss of ascorbic acid for packaging laminda vacuum. The BET model best fit the adsorption isotherms of the lyophilized powder acerola pulp, while for the spray-dryer model Oswin better adjusted to 25 ÂC, and Henderson model for 35 and 45 ÂC. Morphological characterization showed by analysis of Microcopia Scanning Electron (SEM), X-ray diffraction (XRD) spectroscopy and Fourier Transform Infrared (FTIR-ATR) that the lyophilization process generates an amorphous powder and adding maltodextrin protects the frame of samples and permits lower moisture absorption also show similar composition between samples, and a higher absorbance obtained is lyophilized in the whole sample.
O objetivo desta pesquisa foi a obtenÃÃo de pà a partir da polpa de acerola integral por dois mÃtodos de secagem (spray-dryer e liofilizaÃÃo), assim como a determinaÃÃo da estabilidade fÃsico-quÃmica e caracterÃsticas higroscÃpicas e morfolÃgicas. As polpas de acerola foram adquiridas no comÃrcio de Fortaleza-CE. Caracterizou-se a polpa e os pÃs quanto a parÃmetros fÃsico-quÃmicos e colorimÃtricos e morfolÃgicos. O estudo da estabilidade dos pÃs foi realizado em trÃs embalagens distintas por um perÃodo de 90 dias. Determinou-se ainda as isotermas de adsorÃÃo. Os resultados indicaram condiÃÃes Ãtimas de secagem em spray-dryer utilizando temperatura de secagem de 154ÂC e concentraÃÃo de maltodextrina na polpa de 17,1%, enquanto para o liofilizador, 19,1% de maltodextrina com tempo de liofilizaÃÃo de 24 horas. Todos os parÃmetros fÃsico-quÃmicos avaliados na polpa integral sofrem variaÃÃo apÃs secagem. A secagem em spray-dryer gerou pà com menor umidade, e a liofilizaÃÃo gerou um pà mais higroscÃpico, com maior grau de caking, e melhor preservaÃÃo da cor, sendo o pH um parÃmetro de pequena variaÃÃo. O estudo da estabilidade das polpas de acerola em pà obtidas por diferentes mÃtodos de secagem permitiu observar aumento da umidade e das coordenadas a* e b* e diminuiÃÃo do Ãcido ascÃrbico e luminosidade. O uso de embalagens laminada e laminada a vÃcuo mostrou-se eficaz para a manutenÃÃo da umidade e higroscopicidade dos pÃs, com menor perda de Ãcido ascÃrbico para a embalagem laminada a vÃcuo. O modelo de BET melhor se ajustou as isotermas de adsorÃÃo o pà de polpa de acerola liofilizado, enquanto para o spray-dryer o modelo de Oswin melhor se ajustou a 25ÂC, e o modelo de Henderson para 35 e 45ÂC. A caracterizaÃÃo morfolÃgica mostrou pelas anÃlises de Microcopia EletrÃnica de Varredura (MEV), DifraÃÃo de Raios-X (DRX) e Espectroscopia de Infravermelho com Transformada de Fourier (FTIR-ATR) que o processo de liofilizaÃÃo gera um pà amorfo e que a adiÃÃo de maltodextrina protege a estruturadas amostras e permite uma menor absorÃÃo de umidade, ainda mostra composiÃÃo similar entre as amostras, e que uma maior absorbÃncia à obtida em amostra integral liofilizada.

O camu-camu (Myrciaria dubia Mc. Vaugh) tem demonstrado ser um fruto promissor devido ao potencial funcional, principalmente pelo alto teor de vitamina C e compostos fenólicos, em especial elagitaninos. Este trabalho teve como objetivo avaliar os efeitos sobre os compostos fenólicos dos processos de secagem de polpa comercial de camu-camu, por leito de jorro e atomização (spray-drying), em diferentes temperaturas e concentrações de agentes carreadores, comparando-os com os do processo de liofilização. Os pós obtidos foram comparados em relação ao teor total de compostos fenólicos, ácido ascórbico e proantocianidinas. Além disso, avaliou-se o potencial benéfico à saúde através da determinação da capacidade antioxidante in vitro , atividade antimicrobiana e inibição das enzimas α-amilase, α-glicosidase e enzima conversora da angiotensina (ECA). Avaliou-se também proteção e regeneração celulares em modelo de planárias (Dugesia trigrina). Complementarmente, os pós de camu-camu foram adicionados em leite de soja, que foram fermentados com bactérias produtoras de ácido láctico (L. helveticus ATCC 12046 e L. plantarum NCDO 1193), para verificar sua funcionalidade quando incorporados como ingredientes em alimentos funcionais. Os resultados mostraram que a secagem da polpa acarretou em perdas significativas de compostos bioativos, na ordem ácido ascórbico>fenólicos totais> proantocianidinas, e spray-drying>leito de jorro>liofilização. Os compostos fenólicos detectados nos pós de camu-camu foram elagitaninos, ácido elágico, derivados de quercetina, ácido siríngico e miricetina, por LC-TOF-MS. A liofilização foi a melhor técnica de secagem para a preservação dos compostos fenólicos, e também da capacidade antioxidante e de inibição enzimática. Além disso, os pós liofilizados e atomizado (contendo 6% goma arábica a 120 °C) foram mais efetivos contra Staphylococcus aureus que a ampicilina. Os extratos desses pós demostraram potencial para proteção celular e rejuvenescimento no modelo de planárias. E por último, o leite de soja enriquecido com o pó de camu-camu resultou em um produto com maior teor de fenólicos, alta capacidade antioxidante e propriedades anti-hiperglicêmica e anti-hipertensiva. Portanto, os pós de camu-camu são ricos em compostos fenólicos e tem potencial para serem acrescentados como ingredientes em alimentos para o controle dos estágios iniciais de diabetes tipo 2 e complicações associadas.
Camu-camu (Myrciaria dubia Mc. Vaugh) has demonstrated promising perspectives as a functional food, mainly due to high vitamin C and phenolic compounds contents, in particular ellagitannins. This study aimed to evaluate the effect of different drying processes (spouted bed drying, spray-drying) at selected temperatures and carrier concentrations, comparing to freeze-drying, on the contents and composition of phenolic compounds. The pulp powders were compared in relation to phenolic profiles, ascorbic acid and proanthocyanidins contents. Further, functional health potential was evaluated such as in vitro antioxidant capacity, antimicrobial activity and inhibition of α-amylase, α-glucosidase and angiotensin converting enzyme (ACE). It was also investigated cellular protection and regeneration in planaria (Dugesia trigrina) model. Additionally, camu-camu powders were added into soymilk and were fermented by lactic acid bacteria (L. helveticus ATCC 12046 and L. plantarum NCDO 1193) to verify their functionality as a functional food ingredient. The results showed that drying of the pulp led to significant losses of bioactive compounds, in the order ascorbic acid>total phenolics>proanthocyanidins, and spray-drying>spouted bed drying>freeze-drying. Phenolic compounds, such as ellagitannins, ellagic acid, quercetin derivatives, syringic acid and myricetin were detected in camu-camu by LC-TOF-MS. The freeze-drying was the best technique to preserve phenolic compounds, and also antioxidant capacity and enzyme inhibition. Besides that, freeze-dried and spray-dried (6% arabic gum at 120 °C) powders were more effective against Staphylococcus aureus than ampicillin. The extracts of those powders have desmonstrated potential to cellular protection and rejuvenation in planaria model. Finally, soymilk enriched with camu-camu powders resulted in more phenolic contents, high antioxidant capacity and anti-hyperglycemia and anti-hipertension properties product. To sum up, camu-camu powder is rich in phenolic bioactive profiles has potential as part of dietary strategies in the management of early stages of type 2 diabetes and associated complications.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
No norte do Brasil, na região Amazônica se destaca a produção de um queijo artesanal na Ilha de Marajó, Pará Brasil. Este queijo é definido como um queijo não maturado obtido pela fermentação natural do leite de búfala pela sua microbiota autóctone e posterior fusão de sua massa. As bactérias láticas (BAL) oriundas de queijos artesanais contribuem para propriedades sensoriais originais nesses queijos, caracterizando os produtos como únicos e específicos de cada região e preservam uma produção tradicional de importância cultural, econômica e social. Sendo assim, o conhecimento da diversidade de BAL é fundamental para a caracterização deste tipo de queijo. Neste contexto, o objetivo desta tese foi isolar e identificar a diversidade de BAL envolvidas no processamento do Queijo Marajó, bem como avaliar os efeitos da liofilização e da secagem por atomização na preservação de BAL. A caracterização preliminar de cocos e bacilos Gram positivos e catalase negativo permitiu a identificação de 149 isolados de BAL obtidas a partir de amostras de leite de búfala cru, massa fermentada e utensílios envolvidos no processamento do queijo Marajó e 97 cocos de BAL oriundas de amostras do queijo Marajó. Por meio do sequenciamento do gene 16S rDNA oito espécies foram identificadas: Weissella confusa, Streptococcus infantarius, Lactococcus lactis, Leuconostoc pseudomesenteroides, Weissella paramesenteroides, Pediococcus pentosaceus, Pediococcus acidilactici, Lactobacillus brevis e o gênero Enterococcus. A Rep-PCR foi capaz de identificar diferentes perfis genéticos demonstrando uma grande diversidade entre os isolados avaliados. Dentre os isolados, as espécies Lactobacilus plantarum e Lactobacillus paraplantarum também foram identificadas oriundas do queijo Marajó. E uma cepa de L. plantarum foi selecionada para estudos de preservação em processos liofilização e secagem por atomização. As células de L. plantarum submetida à secagem por atomização mantiveram-se aproximadamente em 10 9 UFC∙g -1 , enquanto que as amostras submetidas à liofilização reduziram a viabilidade para 10 7 UFC∙g -1 durante 60 dias de estocagem a 4 °C e 20 °C. Os efeitos da secagem por atomização na viabilidade das células de L. plantarum foram menores que a liofilização. As características fenotípicas apresentadas pelas BAL, neste estudo, permitem direcionar futuras pesquisas para preservação das cepas de BAL envolvidas na produção do Queijo Marajó, bem como desenvolver culturas starter/adjuntas com um elevado número de células viáveis para aplicação industrial por meio da secagem por atomização a um de baixo custo.
Northern Brazil, in the Amazon region stands out in the production of an artisanal cheese on the Marajó Island (Pará, Brazil). It is defined as a fresh cheese obtained through natural coagulation of raw buffalo milk by the autochthonous microbiota and subsequent curd fusion. LAB from artisanal cheeses contribute to original sensory properties in these cheeses, characterizing unique and specific products of each region, preserving a tradition of cultural, economic and social importance. Thus, the knowledge of LAB diversity is fundamental to the characterization of this type of cheese. In this context, the aim of this thesis was to isolate and to identify the LAB biodiversity involved in the production of Marajó cheese and to evaluate the effects of freeze drying and spray drying in the preservation of LAB. Preliminary characterization as Gram positive cocci and/or bacilli and as negative catalase plus identification by using 16S rDNA sequence analysis and Rep-PCR were undertaken for 149 LAB isolates obtained from samples of raw buffalo milk, curd and utensils involved in Marajó Cheese making and 97 LAB cocci from Marajó Cheese. Eight species have been identified as follows: Weissella confusa, Streptococcus infantarius, Lactococcus lactis, Leuconostoc pseudomesenteroides, Weissella paramesenteroides, Pediococcus pentosaceus, Pediococcus acidilactici, Lactobacillus brevis and the Enterococcus genus. The Rep-PCR was able to identify different genetic profile showing a high diversity among the evaluated isolates. Among the isolates, the species Lactobacillus plantarum and Lactobacillus paraplantarum were also identified coming from Marajó cheese. And a strain of L. plantarum was selected for preservation of freeze drying and spray drying.The cells of L. plantarum subject to spray drying process at approximately 10 9 CFU.g -1 , while the freeze dried samples showed 10 7 CFU.g -1 after 60 days of storage at 4°C and 20 °C. The spray drying was less damaging than freeze drying for L. plantarum cells. The phenotypic characteristics showed by LAB isolated in this study allow of directing further investigations to preserve LAB strains involved in production of Marajó cheese in order to produce starter and adjunct cultures by spray drying with a high number of viable cells to be used for industrial application through a cost-effective method.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Spray-drying and freeze-drying are dehydration techniques which serve as alternative to increase the stability of formulations which are in aqueous medium. Therefore, this study objectived the development of redispersible dried products prepared from suspensions of polymeric nanocapsules and nanoemulsions using tioconazole, an antifungal. The suspension of nanocapsules, prepared using poli(-caprolactona) - PCL and Eudragit® RS100 polymers, and nanoemulsions containing tioconazole (1.0 mg/ml) were evaluated in relation to mean particles size, drug content, pH and encapsulation efficiency, and after preparation, showed physicochemical characteristics suitable: mean particles size in the nanometer range (110 210 nm), polydispersity index below 0.20, drug content near to theoretical and encapsulation efficiency of approximately 100 % and 86 % for the PCL and Eudragit® RS100 nanocapsules, respectively. Furthermore, the formulations have been stable for 30 days. After, the liquid formulations were subjected to spray-drying and/or freeze-drying using lactose and trehalose as adjuvants in a proportion of 10 % (w/v). The dried products were characterized in relation to yield, index resuspension in water, drug content, moisture and morphology. Regardless of the method of dehydration and adjuvant, the dried products presented satisfactory physicochemical characteristics: yield 50 100 % (depending on the technique of dehydration), drug content near to theoretical, percentage of moisture of less than 4.2 %, good redispersion in water, is possible to verify the presence of nanometric and micrometric particles (by laser diffraction), and the recovery of nanometer size similar to the original liquid formulation, after filtration (photon correlation spectroscopy). Morphological analysis showed the presence of rounded particles for the powders obtained by spray-drying and irregular to those obtained by freeze-drying. Dried products were stable for 30 days, however, the powders obtained from nanoemulsions and nanocapsules of Eudragit® RS100, by spray-drying and lactose as adjuvant showed a decrease in tioconazole content. The suspensions of nanocapsules and nanoemulsions and their respective dried products containing tioconazole showed antifungal activity against the yeast C. albicans, demonstrating that the dehydration process did not affect the action of the drug. Evaluation of in vitro release of the drug by the technique of dialysis bags showed that dried products prepared from nanocapsules were able to promote the control release of the drug, especially the dried products obtained from nanocapsules of PCL by spray-drying, which showed more tioconazole control release at time of 48 hours.
A secagem por aspersão (spray-drying) e a liofilização são técnicas de desidratação que servem como alternativa para aumentar a estabilidade de formulações que se encontram em meio aquoso. Neste sentido, este trabalho objetivou o desenvolvimento de produtos secos redispersíveis preparados a partir de suspensões de nanocápsulas poliméricas e nanoemulsões utilizando o tioconazol, um fármaco antifúngico. As suspensões de nanocápsulas, preparadas com os polímeros poli(-caprolactona) PCL e Eudragit® RS100, e nanoemulsões contendo tioconazol (1,0 mg/mL) foram avaliadas quanto ao diâmetro médio de partículas, teor de fármaco, pH e eficiência de encapsulamento, as quais, após a preparação, apresentaram características físico-químicas adequadas: diâmetro médio de partículas na faixa nanométrica (110 210 nm), índice de polidispersão abaixo de 0,20, teor de fármaco próximo ao teórico e eficiência de encapsulamentro de, aproximadamente, 100 % e 86 % para as nanocápsulas de PCL e Eudragit® RS100, respectivamente. Além disso, as formulações foram estáveis por 30 dias. Após, as formulações líquidas foram submetidas à secagem por aspersão e/ou a liofilização, utilizando a lactose e a trealose como adjuvantes, na proporção de 10 % (m/v). Os produtos secos foram caracterizados em relação ao rendimento, índice de ressuspensão em água, teor de fármaco, umidade e morfologia. Independente do método de desidratação e do adjuvante, os produtos secos apresentaram características físico-químicas satisfatórias: rendimento de 50 100 % (dependendo da técnica de desidratação), teor de fármaco próximo ao teórico, percentual de umidade inferior a 4,2 %, boa redispersão em água, sendo possível verificar a presença de partículas nanométricas e micrométricas (por difração a laser), e a retomada do tamanho nanométrico semelhante à formulação líquida original, após filtração (espectroscopia de correlação de fótons). Na análise morfológica foi observada a presença de partículas arredondadas para os pós obtidos por spray-drying e irregulares para os obtidos por liofilização. Os produtos secos foram estáveis por 30 dias; todavia, os pós obtidos a partir de nanoemulsões e nanocápsulas de Eudragit® RS100, por spray-drying e lactose como adjuvante, apresentaram um decaimento no teor de tioconazol. As suspensões de nanocápsulas e nanoemulsões e seus respectivos produtos secos contendo tioconazol apresentaram atividade antifúngica frente à levedura de C. albicans, demonstrando que os processos de desidratação não afetaram a ação do fármaco. A avaliação de liberação in vitro do fármaco pela técnica de sacos de diálise demonstrou que os produtos secos preparados a partir de nanocápsulas foram capazes de promover o controle de liberação do fármaco, destacando-se os produtos secos obtidos a partir de nanocápsulas de PCL por spray-drying que apresentaram maior controle na liberação do tioconazol no tempo de 48 horas.

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.

The unsafe use of needles propagates cross infections with bloodborne pathogens and reduces the positive impact of vaccinations on global health. While a plethora of needle-free injection devices exist, the reformulation of protein-based vaccines is largely empirical and costly, which presents a barrier to their widespread clinical application. This thesis contributes to the identification of approaches that facilitate rapid vaccine reformulation and enhance the immunogenicity of needle-free dry-powder vaccines with the help of novel antigen delivery platforms. We hypothesised that the thermodynamic stabilisation of diphtheria toxin mutant 197 (CRM197), a glycoconjugate vaccine carrier protein, may enhance its structural preservation during spray-freeze-drying (SFD), and that its formulation in either soluble, surface-adsorbed, or nanoparticle form impacts the elicited immune response. Differential scanning fluorimetry was used to study the effect of excipients on the thermal stability of CRM197. Dry-powder formulation of CRM197 used i) encapsulation into a thermodynamically stabilising excipient matrix by SFD, ii) surface-immobilisation via physisorption onto a novel potassium-doped hydroxyapatite (kHA) carrier microparticle formed by molten salt synthesis, and iii) chemical conjugation and surface presentation on amphiphilic block copolymer nanoparticles that were incorporated into SFD-powders (SFD-NP). The structural integrity of CRM197 was assessed by size separation in addition to various spectral and thermal analysis methods. The immunogenicity of dry-powder CRM197 formulations was subsequently tested in vivo. The results suggest that the thermodynamic stability of CRM197 in solution does not ensure its structural stability during SFD. While needle-free dermal vaccination with kHA-adsorbed CRM197 induced comparable antibody titres to conventional IM injection of alum-adjuvanted CRM197, needle-free SFD and SFD-NP powders were less immunogenic. The highest mean IgG titre and most balanced Th1/Th2 response was achieved with nanoparticle-conjugated CRM197 by IM, which outperformed the current clinical standard. Therefore, future vaccine design should combine thermodynamic and kinetic stability screening, and place special emphasis on the delivery and structural presentation of the antigen to the immune system.

Lo scopo di questo lavoro di tesi consiste nella produzione e ingegnerizzazione di nuovi sistemi ibridi ottenuti accoppiando nanoparticelle di titania con la microalga Chlorella Vulgaris, per applicazione nel settore del risanamento delle acque reflue. Lo studio è stato rivolto all’ottimizzazione del materiale, il quale integra due proprietà: l’attività fotocatalitica sfruttata per la degradazione degli inquinanti organici conferita dalla titania e la capacità di biosorbimento di metalli pesanti tipica della biomassa. I risultati hanno evidenziato effetti sinergici positivi promossi dalla dispersione della microalga sulla superficie dell’ossido ed in grado di migliorare le performance di biorimediazione del materiale. Al fine di favorire l’applicazione industriale del sistema catalitico preparato, i campioni prodotti in sospensione sono stati ingegnerizzati rimuovendo il solvente tramite tecnologia di Spray-Freeze-Drying. Con l’obiettivo di ottimizzare la formulazione e correlare le proprietà chimico-fisiche dei materiali alle performance ottenute, è stata svolta un’approfondita caratterizzazione sia sulle sospensioni (ELS, DLS) che sui prodotti granulati (BET, SEM-FEG, SEM-EDS). Le prestazioni funzionali dei campioni preparati sono state valutate rispetto alla reazione modello di fotodegradazione della Rodamina B e nell’assorbimento del catione rameico.

The term Nanoceramics is well known in the ceramic field for at least two decades. In this project a detailed study was performed on the synthesis of α-alumina nanopowders. High solids content nanoalumina suspensions were prepared and used to form green bodies using both wet and dry forming routes. The green bodies were then sintered using both conventional single and two-step sintering approaches. Synthesis: Two different synthesis methods, viz. precipitation and hydrothermal treatment, were used to synthesize fine α-alumina powders from aluminium chloride, ammonia solution and TEAH (Tetraethyl ammonium hydroxide). XRD, TEM and FEG-SEM were used to characterise the powders produced. The presence of commercial α-alumina powder as seed particles did not affect the transformation to α-alumina phase during the hydrothermal treatment at 220˚C in either basic or acidic environments. The results obtained from the precipitation route showed that the combined effect of adding α-alumina seeds and surfactants to the precursor solution could lower the transformation temperature of α-alumina from about 1200˚C for unseeded samples to 800˚C, as well as reducing the level of agglomeration in the alumina powders. The difference in transformation temperature mainly resulted from the nucleation process by the α-alumina seeds, which enhanced the θ → α transformation kinetics. The lower level of agglomeration present in the final powders could be due to the surface modifying role of the surfactants preventing the particles from growing together during the synthesis process. By introducing a further high-temperature step for a very short duration (1 minute) to the low-temperature heat treatment route (800˚C/12 h), the unseeded sample with added surfactant transformed into pure α-alumina phase. The newly-added step was shown to be an in-situ seeding step, followed by a conventional nucleation and growth process. The best final powder was compared with a commercial α-alumina nanopowder. Processing of alumina ceramics: The effect of low-molecular weight ammonium dispersants including Dispex-A40, Darvan-C and Dolapix-CE64, on high solids content nanoalumina suspensions was investigated. The nanosuspension prepared using the most suitable dispersant, Dolapix-CE64, was slip cast into ~53% dense, very homogeneous green bodies. This nanosuspension was also spray freeze dried into crushable granules using Freon as a foaming agent. Green compacts with density of ~53.5% were then formed by dry pressing the 2 vol% Freon-added spray freeze dried granules at 40 MPa. Both slip cast and die pressed green bodies were sintered using conventional single-step and two-step routes followed by characterising the density and grain size measurement of final dense compacts. The results have been compared with that of a submicron alumina ceramic prepared using a commercial α-alumina suspension. Highly dense alumina with an average grain size of ~0.6 μm was fabricated by means of spark plasma sintering at 1200˚C. The application of 500 MPa allowed achieving almost fully dense alumina at temperature as low as 1200˚C for 30 minutes with no significant grain growth.

Les nouvelles molécules thérapeutiques présentent la plupart du temps une faible solubilité aqueuse, à l’origine d’une biodisponibilité restreinte lors de leur administration orale. La réduction de taille des cristaux de substance active à l’échelle submicronique (= production de nanocristaux) s’est imposée comme une voie majeure de formulation au cours de ces dernières années.Afin de pallier des problèmes d’instabilité et d’aboutir à des formes solides pratiques d’utilisation pour les patients, une étape de séchage est généralement effectuée après production des nanocristaux en suspension. L’objectif principal de cette étape est de générer un produit présentant à la fois des propriétés facilitant le déroulement d’étapes procédés avales mais aussi et surtout de prévenir l’agrégation des nanocristaux au risque de compromettre leur dissolution après administration.Plusieurs techniques sont aujourd’hui utilisées dans l’industrie pharmaceutique telle que l’enrobage/granulation en lit d’air fluidisé et le spray drying. Parallèlement à l’élaboration d’une « formulation standard » pour ces deux méthodes de référence, deux techniques innovantes de lyophilisation ont été investiguées dans ce travail. La stabilisation de nanocristaux de kétoconazole par cryopelletization et active freeze drying a été démontrée et les paramètres clefs identifiés. Les produits générés par ces deux techniques, respectivement sous forme de pellets ou de poudre fine, ont été comparés à ceux conçus par enrobage en lit d’air fluidisé et spray drying. En conclusion, ces travaux indiquent que la cryopelletization et l’active freeze drying se positionnent comme des procédés d’intérêt de seconde intention, permettant de traiter des cas particuliers (molécules sensibles au stress thermique, à l’humidité et/ou couteuses)
Newly active pharmaceutical ingredients very often suffer from low aqueous solubility, a fact that in many cases can lead to poor oral bioavailability. Nanosizing, referring to drug nanocrystals production by size reduction, has demonstrated over the past few years a great potential to overcome this major issue.Since solid oral dosage forms are generally preferred due to stability reasons and patient convenience, the production of nanocrystals in a liquid medium is usually followed by a drying step. The main objective of this drying step is to generate a product suitable for downstream processing operations while at the same time preventing nanocrystal aggregation which can adversely affect the dissolution performance of the dry product in vivo.Several drying techniques such as spray drying and coating/granulation in fluidized bed have been successfully implemented in the pharmaceutical industry. In this work, two innovative freeze drying techniques were investigated and compared to the two above mentioned reference methods. The suitability of cryopelletization and active freeze drying to stabilize ketoconazole nanocrystals has been demonstrated and the key process parameters identified. The formulations generated by these two innovative techniques in the form of pellets or fine powder particles, respectively, were compared to the previously manufactured by fluidized bed and spray drying. In conclusion, this work presents cryopelletization and active freeze drying as suitable second-line processes with potential to address the drying of formulations containing problematic molecules sensible to thermal stress, moisture and/or presenting high production costs

Amorphous materials are found in pharmaceutical formulations both as excipients and active ingredients. Indeed, these formulations are becoming an essential strategy for incorporating drugs into well-performing solid dosage forms. However, there is an unmet need of better understanding of the microstructure and component interactions in amorphous formulations to be able to design materials with improved functionalities. The aim of this thesis is to give deepened knowledge about structure-mobility-functionality relationships in amorphous for-mulations by studying composites produced from sugars and filler particles. The structure, the mobility, and physical stability of the composite materials were studied using calorimetry, X-ray diffraction, microscopy, spectroscopy, and molecular dynamics simulations. Further, the moisture sorption of the composites was determined with dynamic vapor sorption. The compression mechanics of the composites was evaluated with compression analysis. It was demonstrated that fillers change the overall properties of the amorphous material. Specifically, the physical stability of the composite was by far improved compared to the amorphous sugar alone. This effect was pronounced for formulations with 60 wt% filler content or more. Amorphous lactose that normally recrystallizes within a few minutes upon humidity exposure, could withstand recrystallization for several months at 60% RH in composites with 80 wt% cellulose nanocrystals (CNC) or sodium montmorillonite (Na-MMT). The increased physical stability of the amorphous sugars was related to intra-particle confinement in extra-particle voids formed by the fillers and to immobilization of the amorphous phase at the surface of the fillers. Also, the composite formation led to increased particle hardness for the lactose/CNC and the lactose/Na-MMT nanocomposites. The largest effect on particle hardness was seen with 40-60 wt% nanofiller and could be related to skeleton formation of the nanofillers within the composite particles. The hygroscopicity for the lactose/Na-MMT nanocomposites decreased as much as 47% compared to ideal simple mixtures of the neat components. The nanofillers did not influence the water sorption capacity in the amorphous domains; however, lactose (intercalated into Na-MMT) interacted with the sodium ions in the interlayer space which led to the lowered hygroscopicity of this phase. The thesis advanced the knowledge of the microstructure of amorphous pharmaceutical com-posites and its relationship with pharmaceutical functionalities. It also presented new approaches for stabilizing the amorphous state by using fillers. The concept illustrated here might be used to understand similar phenomena of stabilization of amorphous formulations.

Il lavoro presentato nell’elaborato di tesi ha avuto come obiettivo lo studio di catalizzatori a base di Aquivion® nella reazione di valorizzazione del furfuril alcol a GVL. Il polimero, appartenente alla famiglia delle resine perfluorosolfoniche, mostra dalle caratteristiche superacide ed è stato utilizzato per la creazione di materiali compositi, polimero/ossido inorganico, tramite la tecnica di spray-freeze-drying. Il lavoro si è articolato in diverse fasi, tra cui la sintesi, la caratterizzazione e lo studio dell’attività catalitica dei sistemi preparati in laboratorio. Fra i vari temi analizzati durante l’attività di ricerca, lo studio sulla stabilità termica è stato di centrale importanza. Grazie alla combinazione di diverse tecniche analitiche, è stato possibile determinare con successo l’intervallo di stabilità termica di ogni composito. Numerosi studi sull’effetto della temperatura e del tempo di reazione hanno altresì permesso di chiarire il meccanismo del processo, mettendo in luce alcune importanti relazioni fra gli intermedi coinvolti.

Lo scopo di questo lavoro di tesi è stato lo studio dell’attività fotocatalitica nella reazione di ossidazione selettiva della 5-idrossimetilfurfurale (HMF) di diversi sistemi a base di diossido di titanio. Il lavoro ha comportato la preparazione di una polvere di ossido di titanio nanoparticellare tramite microemulsione. La polvere ottenuta è stata caratterizzata e confrontata con due polveri commerciali (Evonik P25 e Millenium DT51). Successivamente, la titania prepata tramite microemulsione è stata sottoposta a spray-freeze drying per aumentarne l’area superficiale e ridurne la densità. La tecnica di spray-freeze drying è stata poi utilizzata per sviluppare nanocompositi a base di titania, silice e ceria, e per decorare alcune polveri con nanoparticelle di oro e di oro/rame preformate. Le nanoparticelle sono state sintetizzate tramite un processo in acqua a basso impatto ambientale, usando un sistema glucosio-sodio idrossido come riducente e PVP come stabilizzante. Le polveri preparate sono state caratterizzate tramite analisi BET, DRS, XRD, SEM e TEM. Tutti i materiali sviluppati sono stati testati nella reazione di fotoossidazione selettiva dell’HMF utilizzando un simulatore solare. Sono inoltre state svolte prove fotocatalitiche utilizzando scavenger di specie attive, volte ad indagare il meccanismo promosso da alcune delle polveri preparate e le differenze fra questi.

The objective of the experimental thesis work is to study Aquivion and zirconia-based composite catalysts for furfural and furfuryl alcohol valorization to GVL. Aquivion is a perfluorosulphonic resin with superacidic properties, used to synthetize new composite materials through spray-freeze-drying technique. The work has been carried out in different steps, including the synthesis and characterization of zirconia and the catalysts, followed by the study of their catalytic activity. Moreover, reaction parameters have been changed, recording variations in the system and focusing on the acidity of single components and the ratio between them in the final material. Further studies enhanced the clarification of the reaction mechanism and its optimization, through the modulation of calcination temperature, reaction temperature and time.

Drying is an important process for a variety of industries such as pharmaceuticals, food, and chemicals, and produce products with low bulk density, good shelf stability, economical storage and transport, and in some cases unique structural qualities. Of the various drying methods available, freeze-drying is the most beneficial for heat sensitive products that susceptible to thermal degradation. Freezedrying also confers a porous structure on the material result from the voids left after subliming the ice crystals. Freeze-drying however is used mainly for high value products due to the high capital and operational costs. The cycle time of such a drier may take several hours. The spray-freeze-drying process has evolved in an attempt to shorten the freezedrying process time. The process atomises a liquid feed to increase the heat and mass transfer surface area. The spray is then frozen in a very cold gas or a cryogenic liquid to form solid particles, which are then freeze-dried. Some processes incorporate a - fluidised bed freeze-drier to reduce the drying time by forced convection heat and mass transfer. This project aim to develop the Spray Freeze- Drying process and examine the effect of the process on the drying entities and resulting product quality, followed by modelling of the spray freezing operation in an attempt to optimise the operation. This thesis is divided into two main areas of investigations; Spray freezing investigation as an influential on the resulting product size and structure. The experiments performed using Phase Doppler Anemometry technique to measure the particle size distributions and velocities in a specially constructed spray freezing chamber with incorporated windows. A spray freeze-drying chamber was constructed composed of three parts co-current spray freezing, gas - particle separation, and fluidisation freeze-drying unites. Successfully spray characterisation measurement was carried in both ambient and sub-ambient temperatures, producing data of the drop size distribution and velocities from refractive scattered laser PDA measurement. The technique produced valuable information about the spray size distribution and velocity, the application of this technique appear was a novel approach in the spray freezing process measurement. The result were used in the established spray freezing model derived from Pham (1984) freezing model incorporating with a recalescence stage from the Hindmarsh (2003) spray freezing model. The current model predicted the droplet freezing time, which is influenced by the droplet diameter, velocity and freezing gas temperature. The results also shows an agreement between the freezing time predicted and the PDA recognition of bursts rejected due to their possible phase change. The spray-freezing-drying chamber was operated in vacuum conditions to produce freeze-dried whey protein powder. The powder characteristic results shows an physical properties such as density, solubility and particle sizes in comparison to spray drying and cryo-spray freeze-drying. The morphology of the spray freeze-dried whey powder is substantially different to that produced by spray drying and displays a porous microstructure. The operation of the freeze-drying unites requires an further investigation for temperature, pressure, and flow control to maintain the freezedrying.

Resumo: Este projeto teve como objetivo estudar a influência de diferentes processos de desidratação (secagem em leito pulso-fluidizado, atomizador - "spray dryer" e em liofilizador) de polpa de maracujá na qualidade do produto final em pó. Todos estes processos visam à obtenção do produto em pó, apresentando vantagens e desvantagens em nível de manuseio e custos. Entretanto, são escassos na literatura estudos que comparem estes processos com foco na qualidade do produto final. O leite desnatado foi utilizado para avaliar sua eficiência na substituição de parte dos aditivos comumente utilizados na produção deste tipo de produto, como, por exemplo, a maltodextrina e a goma Arábica, os quais têm como função a diminuição das dificuldades tecnológicas encontradas na secagem de sucos de frutas e outros produtos com alta quantidade de açúcar devido à higroscopicidade, termoplasticidade e capacidade de caramelização. Inicialmente, realizaram-se as análises físico-químicas da polpa de maracujá e do leite desnatado, onde foram obtidos resultados muito próximos aos da literatura, sendo que as pequenas diferenças obtidas foram atribuídas à variedade do maracujá utilizado, época e local de cultivo e no caso do leite em pó desnatado, devido provavelmente às diferentes marcas comerciais analisadas na literatura. A secagem da polpa de maracujá sem aditivos, em diversas condições operacionais, levou a um rendimento praticamente nulo, fazendo com que o processo fosse considerado inviável nestas condições. Conseguiu-se obter o pó com a polpa de maracujá e os aditivos no secador por atomização ("spray dryer"). Utilizando a maltodextrina como aditivo, o maior rendimento (23.32%) obtido foi para a proporção de 1:4:4 (polpa de maracujá:maltodextrina:leite desnatado) ou seja, 50% dos sólidos de aditivo substituído por leite desnatado... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The aim of this research was to study the influence of different drying methods (pulsed fluid bed dryer, spray dryer and freeze dryer) of passion fruit pulp in the quality of final powder product. All these processes have the purpose to obtain a powder product, showing advantages and disadvantages in terms of handmade and costs. Nonetheless, the literature has a few studies related to comparison between these processes, focusing final product quality. Skim milk was utilized to evaluate its efficiency on partial substitution of additives commonly used in this kind of processes like maltodextrin and Arabic gum, which have the function of minimizing technologies difficulties in drying fruit juices and other products with high quantity of sugar due to hygroscopicity and termoplasticity in high temperatures and humidity. Initially, physicochemical analysis of passion fruit pulp and skim milk showed values close to those described by literature, with little differences due to passion fruit varieties used, time and place of culture. For skim milk the differences can be explain due to existence of a lot of commercial marks. Drying of passion fruit pulp without additives in many operations conditions had a small yield, becoming process impracticable in these conditions. It was obtained powdered passion fruit and additives in spray dryer. Using maltodextrin the greater yield (23.32%) was obtained for 1:4:4 ratio (passion fruit pulp:maltodextrin:skim milk) that is 50% of solids from additives substituted by skim milk. To Arabic gum the best results (21.96%) was obtained to 1:2:6 (passion fruit pulp:Arabic gum:skim milk) with 75% of solids from additives substituted by skim milk. The total substitution of additives (maltodextrin or Arabic gum) by skim milk also showed good results (15.5%). These better yield were obtained in 120°C and feed flow 0.4 l/h considering ratio of pulp... (Complete abstract click electronic access below)
Orientador: Javier Telis Romero
Coorientador: Carmen Sílvia Fávaro Trindade
Banca: João Borges LAurindo
Banca: Célia Maria Landi Franco
Mestre

L'objectif de cette thèse est la préparation d’aérogels biosourcés ayant des propriétés de super-isolation thermique. Pour cela, nous avons choisi de développer de nouveaux aérogels à base de nanofibres de cellulose (NFC). Les aérogels ont été préparés par lyophilisation. Dans un premier temps, une analyse des paramètres expérimentaux jouant un rôle sur la morphologie et les propriétés physico-chimiques des aérogels a été réalisée afin d’obtenir les meilleures propriétés d’isolation thermique. Avec une suspension de NFC à 2% en masse, sans ajout de sels et sans faire varier le pH, une lyophilisation réalisée dans des moules d’aluminium à une température de -80°C a permis d’obtenir des aérogels ayant une conductivité thermique de 0,024 W/m.K. Afin de diminuer cette conductivité thermique, nous avons choisi de réduire la taille des pores pour obtenir un effet Knudsen. Pour cela, une nouvelle technique de séchage a été proposée : la lyophilisation par pulvérisation. Les aérogels préparés dans les mêmes conditions expérimentales que précédemment avec cette technique ont des propriétés thermiques super-isolantes (0,018 W/m.K) grâce à la nano-structuration du réseau poreux. Finalement, un nouveau dispositif expérimental a été développé pour caractériser plus finement les propriétés thermiques des aérogels. C’est un dispositif transitoire impulsionnel qui permet d'estimer simultanément la contribution de la conduction solide et gazeuse, l'effet radiatif et la diffusivité thermique grâce à un modèle théorique simple. Ce dispositif permettra d’approfondir l’étude complexe du transfert thermique à travers des matériaux poreux semi-transparents tels que les aérogels
The objective of this thesis is the preparation of renewable aerogels having thermal super-insulating properties. To do it, we designed new aerogels from nanofibrillated cellulose (NFC) by freeze-drying. This technique is simple and has the advantage of not using organic solvents. First of all, the parameters playing a role on the aerogel morphology and physico-chemical properties of the aerogels were analyzed to get the best thermal insulating properties. Using 2 wt% NFC suspensions, without addition of salts, keeping the initial pH, the obtained freeze-dried aerogels in alumina molds at -80 °C have a thermal conductivity of 0.024 W/m.K. In order to reduce the pore size and to improve the thermal insulating properties by Knudsen effect, a new drying technique was proposed: the spray freeze-drying. Aerogels prepared in the same experimental conditions with this technique have thermal super-insulating properties (0.018 W/m.K) thanks to the nanostructuration of the porous network. Finally, a new device was designed to characterize more precisely the thermal properties of aerogels. This is an impulsive transient device, which can estimate simultaneously the contribution of solid and gas conduction, the radiative effect and thermal diffusivity using a simple theoretical model. This device will allow studying complex heat transfer through porous semi-transparent materials such as aerogels

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Este projeto teve como objetivo estudar a influência de diferentes processos de desidratação (secagem em leito pulso-fluidizado, atomizador – “spray dryer” e em liofilizador) de polpa de maracujá na qualidade do produto final em pó. Todos estes processos visam à obtenção do produto em pó, apresentando vantagens e desvantagens em nível de manuseio e custos. Entretanto, são escassos na literatura estudos que comparem estes processos com foco na qualidade do produto final. O leite desnatado foi utilizado para avaliar sua eficiência na substituição de parte dos aditivos comumente utilizados na produção deste tipo de produto, como, por exemplo, a maltodextrina e a goma Arábica, os quais têm como função a diminuição das dificuldades tecnológicas encontradas na secagem de sucos de frutas e outros produtos com alta quantidade de açúcar devido à higroscopicidade, termoplasticidade e capacidade de caramelização. Inicialmente, realizaram-se as análises físico-químicas da polpa de maracujá e do leite desnatado, onde foram obtidos resultados muito próximos aos da literatura, sendo que as pequenas diferenças obtidas foram atribuídas à variedade do maracujá utilizado, época e local de cultivo e no caso do leite em pó desnatado, devido provavelmente às diferentes marcas comerciais analisadas na literatura. A secagem da polpa de maracujá sem aditivos, em diversas condições operacionais, levou a um rendimento praticamente nulo, fazendo com que o processo fosse considerado inviável nestas condições. Conseguiu-se obter o pó com a polpa de maracujá e os aditivos no secador por atomização (“spray dryer”). Utilizando a maltodextrina como aditivo, o maior rendimento (23.32%) obtido foi para a proporção de 1:4:4 (polpa de maracujá:maltodextrina:leite desnatado) ou seja, 50% dos sólidos de aditivo substituído por leite desnatado...
The aim of this research was to study the influence of different drying methods (pulsed fluid bed dryer, spray dryer and freeze dryer) of passion fruit pulp in the quality of final powder product. All these processes have the purpose to obtain a powder product, showing advantages and disadvantages in terms of handmade and costs. Nonetheless, the literature has a few studies related to comparison between these processes, focusing final product quality. Skim milk was utilized to evaluate its efficiency on partial substitution of additives commonly used in this kind of processes like maltodextrin and Arabic gum, which have the function of minimizing technologies difficulties in drying fruit juices and other products with high quantity of sugar due to hygroscopicity and termoplasticity in high temperatures and humidity. Initially, physicochemical analysis of passion fruit pulp and skim milk showed values close to those described by literature, with little differences due to passion fruit varieties used, time and place of culture. For skim milk the differences can be explain due to existence of a lot of commercial marks. Drying of passion fruit pulp without additives in many operations conditions had a small yield, becoming process impracticable in these conditions. It was obtained powdered passion fruit and additives in spray dryer. Using maltodextrin the greater yield (23.32%) was obtained for 1:4:4 ratio (passion fruit pulp:maltodextrin:skim milk) that is 50% of solids from additives substituted by skim milk. To Arabic gum the best results (21.96%) was obtained to 1:2:6 (passion fruit pulp:Arabic gum:skim milk) with 75% of solids from additives substituted by skim milk. The total substitution of additives (maltodextrin or Arabic gum) by skim milk also showed good results (15.5%). These better yield were obtained in 120°C and feed flow 0.4 l/h considering ratio of pulp... (Complete abstract click electronic access below)

La sangre obtenida en el matadero es un producto altamente contaminado que requiere un procesamiento inmediato si se pretende utilizarla como insumo alimentario en la fabricación de productos destinados al consumo humano. Si bien es cierto que los sistemas de higienización podrían ser muy eficientes desde el punto de vista de calidad microbiológica, su instalación en la línea de sacrificio comportaría muchas dificultades desde el punto de vista técnico y en algún caso sería muy costoso. La bioconservación podría ser una alternativa para mejorar la calidad microbiológica de la sangre, alargar su vida útil y reducir las posibilidades de procesamiento inmediato.
El presente estudio nos permitiría formular la posibilidad de aplicar la bioconservación en sangre de cerdo procedente de matadero industrial, utilizando bacterias ácido lácticas (BAL) como cultivo bioprotector, para lo cual se aislaron cepas de BAL autóctonas y se confeccionaron dos colecciones una de BAL mesófilas y otra de psicrótrofas.
Se evaluó el potencial antagonista de la colección de BAL mesófilas y psicrótrofas a 30ºC y a 15ºC respectivamente frente a bacterias contaminantes habituales de este subproducto. Las BAL que demostraron antagonismo en placa (7,1% a 30ºC y 11% a 15ºC) fueron seleccionadas para evaluar el potencial antagonista en sangre, donde el efecto inhibitorio se vio favorecido por la adición de un 2% glucosa. S.aureus y P. fluorescens fueron los indicadores más inhibidos por las cepas mesófilas, en algunos casos con reducciones superiores a 7 unidades logarítmicas. En condiciones psicrótrofas la bacteria más sensible a la presencia de BAL fue Bacillus sp., donde 8 de las 11 BAL ensayadas permitieron reducciones superiores a 4 logs y 1cepa incluso superiores a 7 logs; se obtuvieron reducciones máximas de 3 logs de E.coli y Pseudomonas fue inhibida por todas las BAL ensayadas, en algún caso con reducciones superiores a 5 logs.
Las 5 que cepas que presentaron el espectro de inhibición más amplio en condiciones mesófilas y 7 en condiciones psicrótrofas frente a los microorganismos indicadores contaminantes de sangre de matadero se identificaron mediante técnicas moleculares por comparación de la secuencias correspondientes al gen que codifica la síntesis de 16S ARNr (16S ADNr) con las secuencias publicadas en las bases de datos.
De las 7 cepas antagonistas en condiciones psicrótrofas 5 se identificaron como Lactococcus garvieae y 2 como Enterococcus malodoratus/gilvius raffinosus. Todas las BAL con potencial antagonista en condiciones mesófilas pertenecían al género Lactobacillus, 3 de elllas se identificaron como Lactobacillus murinus/animalis y una se identificó como Lactobacillus reuteri. TA20 que tuvo un gran espectro de inhibición a ambas temperaturas se identificó como Lactococcus garvieae.
En este estudio se evaluaron tres métodos de conservación a largo plazo de las cepas que mostraron potencial antagonista. Se comparó la liofilización, la atomización frente a la congelación a -80ºC que era método que se había utilizado hasta el momento para conservar ambas colecciones de BAL. En general, los métodos de deshidratación (atomización y liofilización) y mantenimiento en refrigeración a 5ºC de los cultivos deshidratados se han mostrado más eficaces que la congelación.
Blood from slaughtered animals is a product with a high contamination level that requires an immediately processing after collection if the object is to use it as a food ingredient destined to human consumption. Nevertheless, even if hygienic collection systems used in abattoirs were be efficient enough to control the microbiological quality, their installation in the slaughtered line would be technically complicate and in some case would be so expensive.
Bioconservation is an alternative to improve microbiological quality, to extend its shelf life and reducing the possibility of immediate processing after collection.
The present study would permit us to formulate the possibility to applicate bioconservation in porcine blood from industrial abattoirs, using lactic acid bacteria (LAB) strains as biopreservative cultures. So a mesophylic and a psicrotrophyc LAB strains collections were confectioned.
The antagonistic capacity toward usual contaminant bacteria in blood of the mesophylic and psicrotrophyc collections at 30ºC and 15ºC respectively were investigated. The LAB that demonstrated the widest inhibitory spectrum in agar plate evaluation (7,1% at 30ºC and 11% at 15ºC) were screened in order to evaluate their inhibitory activity in blood, where was observed that the addition of glucose at 2% had a positive effect in the inhibitory levels.
The most sensible indicators to the mesophylic LAB were S. aureus and P. fluorescens. In some cases it was obtained reductions of 7 logarithmic units. In psicotrophic conditions the most sensible bacteria to LAB presence was Bacillus spp. where 8 of the 11 strains assayed inhibited in more than 4 logarithmic units and 1 of them inhibited this indicator in 7 logarithmic units..
It was obtained maxim reductions of 3 logs versus E. coli. P. fluorescens was inhibited by all the assayed strains and in some case it was obtained reductions superior to 5 logs.
The 5 mesophylic and 7 psictrophyc strains that demonstrated the widest inhibitory spectrum toward the indicators microorganisms from abattoir blood were identified using molecular techniques though comparison of the gene sequences that codify the synthesis of 16S RNAr (16S DNAr) with the sequences in the data base.
5 from the 7 strains with antagonistic capacity in psicotrophyc conditions were identified like Lactococcus garvieae and the other two strains were identified like Enterococcus malodoratus/gilvius/raffinosus. All the antagonistic LAB in mesophylic conditions belonged to genus Lactobacillus, 3 of them were identified like Lactobacillus murinus/animalis and one of them as Lactobacillus reuteri. TA20 that had a widest spectrum at both assay temperatures was identified as Lactococcus garvieae.
In this study there were evaluated three methods of conservation of cultures belonged to those LAB that demonstrated antagonistic capacity. It was compared freeze-drying, spray drying against freezing at -80ºC, that is the method used to conserve both LAB collections. Generally, the dehydration methods (freeze-drying and spray drying) and maintaining in refrigeration at 5ºC of dehydrated cultures showed to be better than freezing at -80ºC.

[ES] El proceso de emulsificación de aceites ricos en compuestos bioactivos permite su mejor aplicación y conservación durante el tiempo de almacenamiento. Entre los diversos mecanismos de emulsificación, se destaca el método de Pickering ya que utiliza nanopartículas sólidas naturales en sustitución de los tensioactivos artificiales. Debido a sus propiedades antioxidantes, no toxicidad y disponibilidad, en este trabajo se estudiaron distintas modificaciones del quitosano para su potencial aplicación como partícula de Pickering. Las modificaciones estudiadas fueron la autoagregación, también denominada desprotonación, y el entrecruzamiento con tripolifosfato de sodio. Se evaluó el comportamiento de estas partículas emulsionando aceite de café tostado, un subproducto de la industria de café con un alto contenido de compuestos bioactivos y compuestos volátiles de interés. Posteriormente, se analizaron las propiedades físico-químicas y la estabilidad de las microcápsulas producidas tras el secado de las emulsiones mediante técnicas de secado por atomización y liofilización. Todas las emulsiones se caracterizaron por tener un comportamiento reológico pseudoplástico, sufriendo desintegración a lo largo del proceso de digestión. Las emulsiones formuladas con nanopartículas de quitosano desprotonadas y menor concentración de aceite mostraron una mejor estabilización y, en consecuencia, una mayor bioaccesibilidad de los compuestos fenólicos totales. Las diferentes nanopartículas de quitosano se caracterizaron estudiando su carga superficial, distribución del tamaño de partícula, microestructura y afinidad agua/aceite. A medida que se aumentó la concentración de estas partículas, se afectó positivamente la viscosidad de las emulsiones debido a la formación de una red tridimensional en la fase continua. Las nanopartículas obtenidas al entrecruzar quitosano con tripolifosfato de sodio fueron más pequeñas, dando como resultado emulsiones con gotas más pequeñas. Las emulsiones de Pickering que contenían un 10% de aceite de café tostado se secaron por atomización y se liofilizaron utilizando las diferentes nanopartículas de quitosano estudiadas y maltodextrina como agentes portadores. Las microcápsulas obtenidas tuvieron la humedad, actividad del agua y solubilidad adecuada para su manipulación y almacenamiento. La presencia de nanopartículas de quitosano permitió una mayor retención de aceite en las microcápsulas y mayor eficiencia de encapsulación. Los compuestos bioactivos y las propiedades antioxidantes se conservaron mejor durante la liofilización. Por otro lado, las microcápsulas obtenidas por atomización presentaron mayor protección de estos compuestos durante la digestión. Las microcápsulas formuladas con nanopartículas desprotonadas fueron sometidas a almacenamiento durante 30 días a 25 ºC. Durante el almacenamiento, se evaluó la protección contra la oxidación de lípidos y la liberación de volátiles. Las isotermas de sorción de agua de estas muestras se determinaron también previamente en las condiciones de almacenamiento. Ambas muestras presentaron isotermas del tipo II, lo que permitió un buen ajuste del modelo de GAB a los datos experimentales. La determinación del índice de peróxido y del contenido de dienos conjugados dio lugar a valores adecuados durante el almacenamiento, aunque las muestras liofilizadas presentaron una ligera tendencia a la oxidación debido a la mayor cantidad de aceite superficial. Aunque hubo ligeras diferencias entre las muestras secas, todas mostraron menos pérdida de aromas totales (~28%) en comparación con el aceite no encapsulado (~51%) al final del almacenamiento. Así, se concluyó que las nanopartículas de quitosano estudiadas fueron eficientes para encapsular el aceite de café tostado y preservar sus características frente a la acción de agentes externos.
[CA] El procés d'emulsificació d'olis rics en compostos bioactius permet la seua millor aplicació i conservació durant el temps d'emmagatzematge. Entre els diversos mecanismes d'emulsificació, destaca el mètode de Pickering, ja que utilitza nanopartícules sòlides naturals en substitució als tensioactius artificials. A causa de la seua propietat antioxidant, de la no toxicitat i de la disponibilitat, aquest treball va buscar analitzar el quitosà i les seues modificacions com potencials partícules de Pickering. Les modificacions estudiades van ser la autoagregació, també anomenada desprotonació, i l'entrecreuament amb tripolifosfat de sodi. Es va avaluar el comportament d'aquestes partícules emulsionant oli de cafè torrat, un subproducte de la indústria del cafè amb un alt contingut de compostos bioactius i volàtils d'interès. Posteriorment, es van analitzar les propietats fisicoquímiques i l'estabilitat de les microcàpsules produïdes després de l'assecat de les emulsions mitjançant tècniques d'assecatge per atomització i liofilització. Totes les emulsions tenien un comportament reològic pseudoplàstic, sofrint desintegració al llarg del procés de digestió. Les emulsions formulades amb nanopartícules de quitosà desprotonades i menor concentració d'oli van mostrar una millor estabilització i, en conseqüència, una major bioaccesibilitat als compostos fenòlics totals. Les diferents nanopartícules de quitosà es van caracteritzar estudiant la seua càrrega superficial, distribució del tamany de partícula, microestructura i afinitat aigua/oli. A mesura que es va augmentar la concentració d'aquestes partícules, es va afectar positivament la viscositat de les emulsions a causa de la formació d'una xarxa tridimensional en la fase contínua. Les nanopartícules obtingudes a l'entrecreuar quitosà amb tripolifosfat de sodi van ser més menudes, donant com a resultat emulsions amb gotes més menudes també. Les emulsions de Pickering que contenien un 10% d'oli de cafè torrat es van assecar per atomització i es liofilitzaren utilitzant les diferents nanopartícules de quitosà estudiades i maltodextrina com a agents portadors. Les microcàpsules obtingudes van obtenir una humitat, activitat de l'aigua i solubilitat adequada per a la seua manipulació i emmagatzematge. La presència de nanopartícules de quitosà va permetre major retenció d'oli en les microcàpsules i major eficiència d'encapsulació. Els compostos bioactius i les propietats antioxidants es van conservar millor durant la liofilització. D'altra banda, les microcàpsules obtingudes per atomització presentaren major protecció d'aquests compostos durant la digestió. Les microcàpsules formulades amb nanopartícules desprotonades també van ser sotmeses a la prova d'emmagatzematge durant 30 dies a 25°C. Durant l'emmagatzematge, es va avaluar la seua protecció contra l'oxidació de lípids i l'alliberament de volàtils. Per això, les isotermes de sorció d'aigua d'aquestes mostres es van determinar prèviament en les condicions d'emmagatzematge. Les dues mostres van presentar isotermes de tipus II, el que va permetre un bon ajust del model de GAB a les dades experimentals. L'índex de peròxids i el contingut de diens conjugats van resultar en valors adequats durant l'emmagatzematge, encara que les mostres liofilitzades van presentar una lleugera tendència a l'oxidació a causa de la major quantitat d'oli superficial. Encara que va haver lleugeres diferències entre les mostres seques, totes van mostrar menys pèrdua d'aromes totals (~28%) en comparació amb l'oli no encapsulat (~51%) a la fi de l'emmagatzematge. Així, es va concloure que les nanopartícules de quitosà estudiades van ser eficients per encapsular l'oli de cafè torrat i preservar les seues característiques enfront de l'acció d'agents externs.
[EN] The emulsification process of bioactive-rich oils makes possible their better application and preservation over the storage time. Among the many emulsification mechanisms, the Pickering method has been highlighted as it uses natural solid nanoparticles in replacement of artificial surfactants. Due to the antioxidant properties, non-toxicity and availability, this work aimed at studying chitosan modifications to produce potential Pickering particles. The studied modifications comprised self-aggregation, also called deprotonation, and crosslinking with sodium tripolyphosphate. The performance of these particles was evaluated in the emulsification of roasted coffee oil, a by-product of the coffee industry with a high content of bioactive and volatile compounds of interest. Subsequently, the physicochemical properties and stability of the microcapsules produced after drying the emulsions using spray-drying and lyophilization techniques were analyzed. All emulsions were characterized as shear-thinning, being them destabilized over the digestion process. Emulsions formulated with deprotonated chitosan nanoparticles and lower oil concentrations showed better stabilization and, consequently, greater bioaccessibility of total phenolic compounds. The different chitosan nanoparticles were characterized regarding surface charge, particle size distribution, microstructure and oil/water affinity. Deprotonated chitosan nanoparticles had a larger particle size, which resulted in emulsions with larger oil droplets. As the concentration of these particles increased, the viscosity of the emulsions was positively affected by the formation of a three-dimensional network in the continuous phase. The nanoparticles obtained by crosslinking with sodium tripolyphosphate were smaller, resulting in emulsions with smaller droplets. The viscosity of these emulsions was lower and little affected by the concentration of particles. Pickering emulsions containing 10% roasted coffee oil were spray-dried and freeze-dried, using the different studied chitosan nanoparticles and maltodextrin as carrier agents. The resulting microcapsules showed adequate moisture content, water activity and solubility for subsequent handling and storage. The presence of chitosan nanoparticles resulted in greater oil retention in the microcapsules and higher encapsulation efficiency. Microcapsules obtained by spray-drying had a more regular spherical shape, while the microparticles obtained by freeze-drying were larger with irregular morphology. Bioactive compounds and antioxidant properties were more preserved during freeze-drying. On the other hand, spray drying allowed greater protection of these compounds during the in vitro digestion. The spray- and freeze-dried microcapsules formulated with deprotonated nanoparticles were subjected to the storage test for 30 days at 25 ºC. During storage, their protection against lipid oxidation and volatile release were evaluated. The water sorption isotherms of these samples were previously determined under the storage conditions. Both samples presented type II isotherms, which resulted in a good fitting accuracy of the GAB model to the experimental data. The peroxide index and the conjugated dienes content resulted in adequate values during storage, although the freeze-dried samples showed a slightly higher tendency to oxidation due to the higher amount of surface oil. Although slight differences were observed between the dried samples, both of them showed less loss of total volatile compounds (~28%) when compared to the non-encapsulated oil (~51%) at the end of storage. Thus, it was concluded that the studied chitosan nanoparticles were efficient to encapsulate roasted coffee oil and to preserve its characteristics against the action of external agents.
The authors would like to thank the project RTI-2018-099738-B-C22 from the ‘Ministerio de Ciencia, Innovación y Universidades’, the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) - (Finance Code 001; Grant number 88887.468140/2019-00) and the São Paulo Research Foundation (FAPESP – Grant number 2016/22727-8) for the financial support.
Franco Ribeiro, E. (2021). Microencapsulation of roasted coffee oil from chitosan nanoparticles-stabilized Pickering emulsions [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/163234
TESIS

The objective of this research is to further define the relationship between the charge state of insulin, and the self assembly properties of insulin and PEGylated insulin in solution. Polyethylene glycol (PEG) chains were covalently attached to insulin in order to evaluate their impact on insulin's systemic duration of action after pulmonary dosing. This thesis will focus on the assembly properties of the PEG-insulin and insulin, and also demonstrate how the charge state, which was modified by the covalent attachment of PEG, relates to different modes of behavior by anion and cation exchange chromatography. In addition, explain how modifying the assembly state extends to improving formulation properties of spray-dried insulin powders. This thesis is an investigation into the relationship of insulin's charge state controlled by pH and how the charge state affects the self assembly of insulin, especially when the zinc ion is removed. Ionic interaction is one of the major forces affecting insulin assembly. The theory that a change in the charge state of insulin could modulate the ionic interaction and reduce hexamer formation at alkaline conditions was investigated. Experiments were designed to measure the level of hexamer with light scattering, and the amount of hexamer was then correlated with the pH and zinc content of the solutions. The importance of the charge state of the monomer and its behavior extends to chromatography and purification modes as well. Specifically, the purification of various species of PEGylated insulin presents a challenge. By varying mobile phase pH which induces the charge to insulin, an ion exchange method demonstrated very high resolution and controllable interaction between the ion exchange media and the insulin derivatives. A highly accurate method for determining molecular weight and thus the average associated state of insulin in solution has been developed using the MALS (Multi-Angle Light Scattering). Insulin concentration, pH, and metal ion concentrations, were in pharmaceutically relevant ranges. The MALS method was developed to evaluate how the parameters above affect the self-assembly properties of insulin, and use the assembly properties to improve formulations of insulin or PEGylated insulin. To use the light scattering technique the dn/dc (change in refractive index with change in concentration) is required. During the method development, the dn/dc of insulin was measured at 690 nm, and a value of 0.185 mL/g based on theory was confirmed. A novel approach for preparing insulin powders with improved chemical stability, based on maintaining the dissociation of hexamers in solution during the spray drying process was developed. The mode presented here is to remove the zinc ions from solution, increase the pH from 6.6 to 7.8, and maintain a low concentration of insulin approximately 2 to 15 mg/mL. Each of these factors alone decreases the hexamer population in solution, but by combining all three factors, hexamers are driven to very low levels of equilibrium. The increased stability of the powders is predominately related to the decrease in covalent insulin dimer (CID). The data presented correlates a reduced hexamer population in the solution with lower levels of CID's in the dry powder compared to controls. The CID formation rate was reduced by 40% compared to a control.

Le son et la paille de blé, riches en hémicelluloses, sont deux co-produits de la récolte de blé, abondants et renouvelables, mais qui restent à mieux valoriser. Dans le but d'extraire ces hémicelluloses, possédant plusieurs propriétés intéressantes (filmogènes, épaississantes, émulsifiantes, stabilisantes…), un procédé de fractionnement a été élaboré. Ce procédé consiste, après extraction alcaline, en la purification des extraits hémicellulosiques obtenus. Deux techniques ont été appliquées : l'ultrafiltration et la chromatographie sur résine échangeuse d'anions. L'ultrafiltration a permis de concentrer les extraits d'hémicelluloses et de les purifier en éliminant dans le perméat la plupart des molécules contaminantes, essentiellement les sucres libres et les sels minéraux. Les principales limitations de cette étape étaient la viscosité des extraits et les phénomènes de polarisation de concentration et de colmatage des membranes. La percolation sur résine, quant à elle, a permis de décolorer les extraits et de produire des poudres d'hémicelluloses plus claires en fixant certaines molécules colorées telles que les molécules possédant des groupements phénoliques. La combinaison des deux techniques a permis de produire des hémicelluloses pures à 60%. L'extrapolation du procédé à l'échelle pilote par l'utilisation d'un extrudeur bi-vis a permis d'obtenir des poudres d'hémicelluloses pures à 40%
Wheat bran and wheat straw are two by-products abundant and renewable, rich in hemicelluloses, but still not well valued. In order to extract these hemicelluloses characterized by their several interesting properties (film-forming, thickening, emulsifying, stabilizing…), a fractionation process was developed. This process consisted, after alkaline extraction, to purify the hemicellulosic extracts obtained. Two techniques were used: ultrafiltration and chromatography on anion exchange resin. The ultrafiltration allowed to concentrate the extracts and to purify them by removing in the permeate, the contaminating molecules, mostly free sugars and minerals. The main limiting factors of this stage were the extracts viscosity and the fouling of the membranes. The percolation on the resin discoloured the extracts and allowed to produce hemicellulosic powders with lighter colours and that by capturing the coloured compounds such as molecules with phenolic groups. The combination of the two techniques allowed the production of purified hemicelluloses; the purity was about 60%. The extrapolation of the process at a pilot scale using a twin-screw extruder allowed to obtain hemicelluloses with a purity of 40%

Thesis (M.S.)--University of Wisconsin--Madison, 1996.
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Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014
The administration of drugs to the lung by inhalation is a very attractive approach, primarily due to the characteristics of the target organ, the lung. Besides the use of pulmonary delivery for the treatment of local diseases such as asthma, the huge surface area of the lungs, the thin epithelium and the large and constant blood supply mean that it's also an interesting way to deliver drugs meant for systemic absorption. One way to get the drugs to the lungs is by way of dry powder inhalation. However, due to the morphology of the airways, particles meant for inhalation need to have some characteristics to make it possible. Most important is their size, but other factors such as shape also affect the aerodynamic behavior of powder particles. This work explores the methods and technologies that can be used to produce powders for oral inhalation, the characteristics of the particles they produce and possible new approaches for the future. It concludes that the most used are pulverization, particularly jet-milling, and spray-drying but that other technologies, such as freeze-spray-drying and crystallization can also be used. More recently, these technologies have been used in novel ways and for the administration of biopharmaceuticals.

Mestrado em Engenharia Alimentar - Instituto Superior de Agronomia
The essential oils (EO) in general and of oregano (Origanum virens L.) in particular are usually very unstable. Thus, the present study intends to study the potential of encapsulation of EO on matrices obtain from gelatin/sucrose systems, by spray-drying and freeze-drying. Several analytical techniques (scanning electron microscopy, confocal fluorescence microscopy, FTIR and diffusion) were used for morphological evaluation of the encapsulated and the presence of EO in the matrices. In the case of encapsulation by spray-drying, size average particles were also considered, witch, with more frequency, presented sizes between 0.9 and 10 micrometers. The spray-drying encapsulated were smooth and spherical capsules, while those obtained by freeze-drying had no shape or defined structure. The EO presence in the encapsulated was confirmed by FTIR and confocal fluorescence microscopy analysis. It was found that the encapsulated obtained by the spray-drying process had a low value of diffusion coefficient (≈ 10-15 m2/s) and that during the first two hours, the release of EO was greater (0.2 to 0.4 mg) of those encapsulated by freeze drying (0.025 to 0.2 mg). The encapsulation of oregano EO on gelatin/sucrose systems through spray-drying or freeze-drying can be a viable process.-------------------------------------Os óleos essenciais (OE) em geral e o de orégão (Origanum virens L.) em particular são geralmente muito instáveis. Assim, pretendeu-se com o presente trabalho estudar a potencialidade do encapsulamento de OE de orégão em matrizes obtidas a partir de sistemas de gelatina/sacarose, por atomização e liofilização. Foram utilizadas várias técnicas analíticas (SEM, microscopia confocal de fluorescência, FTIR e Difusão) para a avaliação morfológica dos encapsulados e detecção da presença do OE nas matrizes. No caso dos encapsulados por atomização, foi ainda analisado o tamanho médio das partículas que com maior frequência apresentaram tamanhos entre 0,9 e 10 μm. Os encapsulados por atomização apresentavam-se na forma de cápsulas lisas e esféricas, enquanto os obtidos por liofilização não apresentavam forma ou estrutura definida. A presença de OE nos encapsulados foi corroborada por análise FTIR e microscopia Confocal de fluorescência. Verificou-se que os encapsulados obtidos por atomização apresentaram um baixo valor de coeficiente de difusão (≈10-15m2/s) e que, durante as primeiras duas horas, libertavam maior quantidade de OE (0,2 a 0,4 mg) do que os encapsulados por liofilização (0,025 a 0,2 mg). O encapsulamento de OE de orégão em sistemas gelatina/sacarose através da atomização ou da liofilização pode constituir um processo viável.

Mestrado em Engenharia Alimentar - Qualidade e Segurança Alimentar - Instituto Superior de Agronomia
Inulin and fructo-oligosaccharides are prebiotic compounds and, for that reason, the growing interest in these natural constituents has been increasing in the last decade, raising the attention of food industry. On the other hand, their properties, namely the ability of capsule formation, allow their use as encapsulation material. This thesis was to study inulin as an encapsulating matrix of bioactive compounds, for what there were used drying processes by spray-drying and freeze-drying. The tests done have shown that the atomization process is the most efficient in the formation of inulin capsules. The size of the particles formed, ranged between 3 and 5 μm, and it was observed that their size decreases as the polymerization degree increases. So, to optimize the particles’ size and other characteristics, there were tested different drying conditions, and so it was done an inulin matrix. The concentration of soluble solids and the drying temperature were the studied variables. Trough the response surface methodology, it was verified that both variables have influence on the particles’ size, although the solids concentration showed a bigger influence. The encapsulation of oregano oil has showed that inulin is an effective encapsulating agent.-------------------------------------A inulina e os FOS são compostos prebióticos, e deste modo o crescente interesse nestes constituintes naturais tem aumentado na última década, e suscitado a atenção por parte da indústria alimentar. Por outro lado, as suas propriedades, nomeadamente a capacidade de formação de cápsulas, permite a sua utilização como agente encapsulante. A presente dissertação pretendeu estudar a inulina, como matriz encapsulante de compostos bioactivos, para o que se recorreu a processos de secagem por liofilização e atomização. Os ensaios efectuados mostraram que o processo de atomização é o mais eficaz na formação de cápsulas de inulina. O diâmetro médio das partículas formadas variou entre 3 e 5 μm, e observou-se que o diâmetro diminui à medida que o grau de polimerização aumenta. De forma a optimizar o diâmetro e outras características das partículas, foram testadas diferentes condições de secagem, elaborando-se uma matriz de inulina. A concentração de sólidos solúveis e a temperatura de secagem foram as variáveis estudadas. Através da metodologia de superfície de resposta, verificou-se que ambas as variáveis têm influência sob o diâmetro de partícula, mas a concentração de sólidos apresentou uma maior influência. O encapsulamento do óleo de orégão comprovou que a inulina é um eficiente agente encapsulante.