No presente trabalho foi realizado o isolamento da 3-O-metilquercetina, a partir de produto seco do extrato de inflorescências de Achyrocline satureioides, e sua caracterização. Em etapa farmacotécnica, foi realizado o estudo da associação deste flavonóide com b-ciclodextrina, bem como testes preliminares de permeação cutânea das associações, incorporadas ou não em gel de hidroxipropilmetilcelulose. As técnicas espectroscópicas, infravermelho e ressonância magnética de hidrogênio, confirmaram a estrutura do flavonóide isolado. Para o doseamento da 3-Ometilquercetina, realizou-se a validação de metodologia analítica por cromatografia líquida de alta eficiência, obtendo-se linearidade, na faixa de concentração de 0,05 a 1,5 μg/mL, precisão e exatidão adequadas. A análise da associação da 3-Ometilquercetina com b-ciclodextrina por infravermelho, ressonância magnética de hidrogênio e a análise pelo método empírico de Mecânica Molecular (MM2) do software Chem3D Ultra (Versão 9.0, CambridgeSoft) indicam possível inclusão do anel B da 3-O-metilquercetina na cavidade da b-ciclodextrina, sendo a inserção do flavonóide pela borda das hidroxilas secundárias mais favorável do que pela borda das hidroxilas primárias. A b-ciclodextrina e o gel de hidroxipropilmetilcelulose promoveram a permeação do flavonóide através da pele. A realização de ensaios in vivo para a seleção da melhor formulação constitui-se na principal perspectiva de continuidade de investigação científica do tema. / 3-O-methylquercetin (3-OMQ) was isolated from spray dried powder of Achyrocline satureioides and characterized by IR and 1H NMR. The study of association of this flavonoid with b-cyclodextrin (bCD) was performed, as well as preliminary skin permeation tests of these associations, incorporated or not in hydroxypropyl methylcellulose (HPMC) hydrogel. A LC method for 3-OMQ assay was validated in the concentration range from 0.05 to 1.5 μg/mL, with suitable precision and accuracy. The complexation of 3-OMQ with bCD was analyzed by IR, 1H NMR and Molecular Mechanics (Chem3D Ultra 9.0, CambridgeSoft) and the results indicated the possible insertion of B ring of the flavonoid into the bCD cavity, being the insertion through the secondary OH rim more favorable than through the primary OH rim. bCD and HPMC promoted the permeation of the flavonoid through the skin. In vivo assay is required to select the appropriate formulation.

No presente trabalho foi realizado o isolamento da 3-O-metilquercetina, a partir de produto seco do extrato de inflorescências de Achyrocline satureioides, e sua caracterização. Em etapa farmacotécnica, foi realizado o estudo da associação deste flavonóide com b-ciclodextrina, bem como testes preliminares de permeação cutânea das associações, incorporadas ou não em gel de hidroxipropilmetilcelulose. As técnicas espectroscópicas, infravermelho e ressonância magnética de hidrogênio, confirmaram a estrutura do flavonóide isolado. Para o doseamento da 3-Ometilquercetina, realizou-se a validação de metodologia analítica por cromatografia líquida de alta eficiência, obtendo-se linearidade, na faixa de concentração de 0,05 a 1,5 μg/mL, precisão e exatidão adequadas. A análise da associação da 3-Ometilquercetina com b-ciclodextrina por infravermelho, ressonância magnética de hidrogênio e a análise pelo método empírico de Mecânica Molecular (MM2) do software Chem3D Ultra (Versão 9.0, CambridgeSoft) indicam possível inclusão do anel B da 3-O-metilquercetina na cavidade da b-ciclodextrina, sendo a inserção do flavonóide pela borda das hidroxilas secundárias mais favorável do que pela borda das hidroxilas primárias. A b-ciclodextrina e o gel de hidroxipropilmetilcelulose promoveram a permeação do flavonóide através da pele. A realização de ensaios in vivo para a seleção da melhor formulação constitui-se na principal perspectiva de continuidade de investigação científica do tema. / 3-O-methylquercetin (3-OMQ) was isolated from spray dried powder of Achyrocline satureioides and characterized by IR and 1H NMR. The study of association of this flavonoid with b-cyclodextrin (bCD) was performed, as well as preliminary skin permeation tests of these associations, incorporated or not in hydroxypropyl methylcellulose (HPMC) hydrogel. A LC method for 3-OMQ assay was validated in the concentration range from 0.05 to 1.5 μg/mL, with suitable precision and accuracy. The complexation of 3-OMQ with bCD was analyzed by IR, 1H NMR and Molecular Mechanics (Chem3D Ultra 9.0, CambridgeSoft) and the results indicated the possible insertion of B ring of the flavonoid into the bCD cavity, being the insertion through the secondary OH rim more favorable than through the primary OH rim. bCD and HPMC promoted the permeation of the flavonoid through the skin. In vivo assay is required to select the appropriate formulation.

The aim of this doctoral thesis is to verify a possibilities of fibercement extrusion. A mixture for extrusion is typical for its high toughness and high fiber content, as the fiber content may be several times higher than when utilizing other production methods. The technology of a twin shaft kneader makes it possible to produce homogenous mixture for extrusion with low water/cement ratio. With use of auger moulder a mixture of high toughness is formed to final shape. The extreme shear and pressure stress is applied in the process. Therefore high requirements are posed on the equipment.

Polymers with mucoadhesive properties are universally used in the development of mucoadhesive drug delivery system. Their physicochemical properties as well as the mechanisms related to their adhesive actions draw great attention for the modification of mucoadhesive properties. In this study, relationships between physicochemical properties of hydroxypropyl methylcellulose (HPMC) compacts and mucoadhesive performance were investigated. Different commercial grades of HPMC (K3, E3, E5, E50, K4M, E4M and K15M) were prepared into compacts, and their surface hydrophilicity and hydration behavior were characterized. The in vitro mucoadhesive performance was determined by the tension strength between the compacts and different regions of mucous membrane (buccal, sublingual, stomach, and intestine). Positive correlations were found between: (1) viscosity of HPMC compacts and contact angle values measured by different simulated body fluids; (2) viscosity of HPMC compacts and in vitro mucoadhesive force; (3) contact angle values and in vitro mucoadhesive force. The hydration behavior exhibited improvement with the increasing viscosity of HPMC compacts. Moreover, the polar lipid content of each mucosa was likely an important factor affecting the mucoadhesion phenomenon. Different ratios of ethyl cellulose (EC) was mixed with HPMC grade K15M to form combination compacts for the purpose of modifying the surface property. The mucoadhesive mechanism of both different grades of HPMC compacts and combination compacts were studied via the thermodynamic analysis of Lifshiz-van der Waals interaction and Lewis acid-base interaction. The total free energy of adhesion (〖∆G〗^TOT) provided a prediction of an overall tendency of mucoadhesion, however, the results were showing disagreement with the measured mucoadhesive force. In general, the involving of EC in the combination compacts did not give a boost to the whole mucoadhesive performance.

La fonctionnalisation d'emballages biodégradables avec des antioxydants naturels est l'une des techniques prometteuses pour améliorer la conservation des aliments, diminuer la quantité de conservateurs chimiques utilises, protéger la dégradation aromatique des produits et ainsi conserver une meilleure qualité globale. Le contrôle du relargage de ces composés actifs de l'emballage vers l'aliment permet d'étendre l'efficacité de la fonctionnalisation en libérant progressivement les antioxydants à la surface de l'aliment. L'objectif global de ce travail était de fonctionnaliser le polymère HPMC afin de produire un film d'emballage coloré à activité antioxydante et d'évaluer son aptitude à servir d'emballage actif. Tout d'abord, des films d'HPMC contenant différents colorants synthétiques comme le bleu, le vert, le jaune, le rouge et le blanc ont été testés afin de déterminer la couleur la plus adaptée pour le contrôle de la photo-oxydation de produits gras. Ensuite, la couleur rouge synthétique, montrant un maximum de contrôle contre la photo-oxydation, a été remplacée par des composés actifs naturels de même couleur. Ces composés provenaient soit d'un mélange d'extraits de betterave et de carottes pourpres, d'un mélange de bétalaïnes soit d'un mélange d'anthocyanes. Le mode d'incorporation de ces composés actifs dans la matrice d'HPMC, leurs effets sur les propriétés thermiques, mécaniques, barrière et structurales des films ont été étudiés. Les résultats ont montré que l'intégration de ces différents composés actifs naturels a permis d'améliorer les propriétés des films. Les composés actifs utilisés ont la capacité de contrôler le photo-vieillissement de la matrice polymérique et que l'HPMC est un bon candidat pour incorporer ces molécules et permettre le contrôle de la dégradation de produits alimentaires riches en lipides / Biodegradable packaging functionalized with natural antioxidants is one of the promising techniques to enhance foods shelf-life, lower use of preservatives in food formations, higher protection of flavours and higher food qualities. Controlled release of these bioactive compounds from packaging to food surface provides longer food stability by continuously librating antioxidants at food surface. The overall objective of the present work was to functionalize the HPMC polymer as colored antioxidant packaging and investigate its suitability as active packaging for unsaturated lipids. Firstly, HPMC films containing different synthetic colours like blue, green, yellow, red and white were tested to chose a suitable color having control against photo-oxidation. Secondly, red synthetic color (showing maximum control against pho-oxidation) was replaced by natural active red compounds including "natural red color" (beetroot extract + purple carrot extract), betalains and anthocyanins to produce bioactive food packaging. Mode of incorporation of these active compounds in HPMC matrix and also their potential effects on thermal, mechanical, barrier and structural properties of films were investigated. Controlled release kinetics, antioxidant capacity and light stability of bioactive compounds in HPMC films were also investigated. The overall results showed that successful incorporation of different natural active compounds have capability to improve film properties. The active compounds under discussion have ability to control photo ageing of polymer matrix and HPMC has the capability for being a suitable carrier for antioxidant active packaging for some food products

Aerogéis de hidroxipropil metilcelulose (HPMC) com diferentes graus de substituição por grupos metila (DS) e hidroxipropila (MS) foram preparados por liofilização utilizando diferentes ácidos como agentes de reticulação, a saber: ácido cítrico, ácido oxálico e ácido tereftálico. Nanocristais de celulose bacteriana (BCN) neutros e negativamente carregados foram utilizados como carga de reforço nas concentrações de 5% (m/m) e 15% (m/m) em relação à massa da matriz. Os resultados indicaram que HPMCs com menores valores de DS e maiores valores de MS resultam em aerogéis com maior eficiência na reticulação. Além disso, agentes de reticulação insolúveis em água minimizaram a capacidade de reticulação, enquanto agentes de reticulação com uma maior quantidade de grupos funcionais ácidos aumentaram a probabilidade e a eficiência da reação de reticulação das cadeias de HPMC. Os aerogéis apresentaram alta estabilidade em água, solventes orgânicos e meio ácido, além de apresentar resiliência quanto à deformação em meio aquoso. Os aerogéis apresentaram porosidade de ~98%, densidade média variando de 0,021 à 0,026 (± 0,002) g.cm-3, módulo de Young variando de 101 à 150 (± 19) kPa e capacidade média de absorção de água de 18 g de água/g de aerogel. A adição de carga de reforço resultou em um aumento de até 13% na densidade aparente do aerogel e um aumento médio de 20% no módulo de Young dos materiais. A morfologia dos poros dos aerogéis sintetizados é irregular, com ampla faixa de distribuição de tamanho de poros, podendo variar cerca de 5 µm a 500 µm. Nos aerogéis reforçados, as BCNs encontram-se preferencialmente no interior das paredes dos aerogéis, onde o reforço mecânico é mais eficiente. Isotermas de adsorção de 17α-etinilestradiol (EE) foram realizadas, resultando em capacidades de remoção de até 90%, com possibilidade de reciclo. As isotermas indicam que a matriz HPMC J5MS possui maior afinidade para adsorção de EE e que a adição de BCNs aumenta a afinidade das moléculas pelo substrato. As isotermas foram melhor ajustadas com o modelo de Freundlich, indicando que a adição de 5% de BCNs aumenta a capacidade de adsorção do aerogel, enquanto a adição de 15% de BCNs provoca uma diminuição nesta propriedade. / Aerogels of Hydroxypropyl methylcellulose (HPMC), with different degrees of substitution for methyl groups (MS) and hydroxypropyl groups (DS) were prepared by freeze-drying. The HPMCs were combined with three organic acids as crosslinking agents: citric acid, oxalic acid and terephthalic acid. Bacterial cellulose nanocrystals (BCN) neutral and negatively charged were used as reinforcement particles from 5% to 15% m/m in relation to the polymer mass. The results indicated that HPMC with lower DS and higher MS levels result in aerogels with higher crosslink efficiency. Besides that, crosslinking agents that are water insoluble minimized the crosslinking capacity, while crosslinking agents with more functional acid groups presented higher probability and efficiency in the crosslinking reaction. The aerogels presented high stability in water, organic solvents and acid media, and presented mechanical resilience in aqueous media. The resulting aerogels presented porosity of ~98%, average density of 0.021 to 0.026 (± 0.002) g.cm-3, Young modulus of 101 to 150 (± 19) kPa and an average capacity of water absorption of 18 g of water/g of aerogel. The addition of reinforcement particles resulted in an increase in density up to 13% and an average increase in the Young modulus of 20%. The morphology of the aerogels was irregular, with a wide pore size distribution, varying between de 5 µm a 500 µm. In the reinforced aerogels, the BCNs were found preferably inside the aerogels walls, were the mechanical reinforcement is more efficient. Adsorption isotherms of 17 ethinyl estradiol (EE) revealed removal capacity up to 90% and possibility of adsorbent recycling. The isotherms indicated that the HPMC J5MS has higher affinity for EE molecules and that the use of BCNs increases aerogels affinity. The isotherms were well fitted with the Freundlich model, indicating that the addition of 5% BCN increases the adsorption capacity of the aerogels, while the addition of 15 % BCN results in a decrease in this property.

Aerogéis de hidroxipropil metilcelulose (HPMC) com diferentes graus de substituição por grupos metila (DS) e hidroxipropila (MS) foram preparados por liofilização utilizando diferentes ácidos como agentes de reticulação, a saber: ácido cítrico, ácido oxálico e ácido tereftálico. Nanocristais de celulose bacteriana (BCN) neutros e negativamente carregados foram utilizados como carga de reforço nas concentrações de 5% (m/m) e 15% (m/m) em relação à massa da matriz. Os resultados indicaram que HPMCs com menores valores de DS e maiores valores de MS resultam em aerogéis com maior eficiência na reticulação. Além disso, agentes de reticulação insolúveis em água minimizaram a capacidade de reticulação, enquanto agentes de reticulação com uma maior quantidade de grupos funcionais ácidos aumentaram a probabilidade e a eficiência da reação de reticulação das cadeias de HPMC. Os aerogéis apresentaram alta estabilidade em água, solventes orgânicos e meio ácido, além de apresentar resiliência quanto à deformação em meio aquoso. Os aerogéis apresentaram porosidade de ~98%, densidade média variando de 0,021 à 0,026 (± 0,002) g.cm-3, módulo de Young variando de 101 à 150 (± 19) kPa e capacidade média de absorção de água de 18 g de água/g de aerogel. A adição de carga de reforço resultou em um aumento de até 13% na densidade aparente do aerogel e um aumento médio de 20% no módulo de Young dos materiais. A morfologia dos poros dos aerogéis sintetizados é irregular, com ampla faixa de distribuição de tamanho de poros, podendo variar cerca de 5 µm a 500 µm. Nos aerogéis reforçados, as BCNs encontram-se preferencialmente no interior das paredes dos aerogéis, onde o reforço mecânico é mais eficiente. Isotermas de adsorção de 17α-etinilestradiol (EE) foram realizadas, resultando em capacidades de remoção de até 90%, com possibilidade de reciclo. As isotermas indicam que a matriz HPMC J5MS possui maior afinidade para adsorção de EE e que a adição de BCNs aumenta a afinidade das moléculas pelo substrato. As isotermas foram melhor ajustadas com o modelo de Freundlich, indicando que a adição de 5% de BCNs aumenta a capacidade de adsorção do aerogel, enquanto a adição de 15% de BCNs provoca uma diminuição nesta propriedade. / Aerogels of Hydroxypropyl methylcellulose (HPMC), with different degrees of substitution for methyl groups (MS) and hydroxypropyl groups (DS) were prepared by freeze-drying. The HPMCs were combined with three organic acids as crosslinking agents: citric acid, oxalic acid and terephthalic acid. Bacterial cellulose nanocrystals (BCN) neutral and negatively charged were used as reinforcement particles from 5% to 15% m/m in relation to the polymer mass. The results indicated that HPMC with lower DS and higher MS levels result in aerogels with higher crosslink efficiency. Besides that, crosslinking agents that are water insoluble minimized the crosslinking capacity, while crosslinking agents with more functional acid groups presented higher probability and efficiency in the crosslinking reaction. The aerogels presented high stability in water, organic solvents and acid media, and presented mechanical resilience in aqueous media. The resulting aerogels presented porosity of ~98%, average density of 0.021 to 0.026 (± 0.002) g.cm-3, Young modulus of 101 to 150 (± 19) kPa and an average capacity of water absorption of 18 g of water/g of aerogel. The addition of reinforcement particles resulted in an increase in density up to 13% and an average increase in the Young modulus of 20%. The morphology of the aerogels was irregular, with a wide pore size distribution, varying between de 5 µm a 500 µm. In the reinforced aerogels, the BCNs were found preferably inside the aerogels walls, were the mechanical reinforcement is more efficient. Adsorption isotherms of 17 ethinyl estradiol (EE) revealed removal capacity up to 90% and possibility of adsorbent recycling. The isotherms indicated that the HPMC J5MS has higher affinity for EE molecules and that the use of BCNs increases aerogels affinity. The isotherms were well fitted with the Freundlich model, indicating that the addition of 5% BCN increases the adsorption capacity of the aerogels, while the addition of 15 % BCN results in a decrease in this property.

[EN] Different strategies were used to improve physical properties of corn starch based films, with glycerol (30%) as plasticizer, based on increasing their hydrophobic character in order to reduce the materials' water sensitivity. Starch was blended with different components (surfactants and more hydrophobic polymers), with and without compatibilizers, to obtain blend films through different processing techniques (casting, melt blending, compression molding and extrusion). Bilayer film formation by compression molding with starch and poly(e-caprolactone) (PCL) was also studied. The addition of surfactants to starch films obtained by casting gave rise to a decrease in water vapor permeability (WVP), but an increase in the film fragility was observed. Surfactants with lower hydrophilic-lipophilic balance (HLB), solid at room temperature, promoted a fine microstructure in the matrix with smaller lipid particle, which enhanced water vapor barrier properties. Thermo-processing was used to obtain the other films due to its broader industrial application. Starch blends with hydroxypropyl methylcellulose (HPMC) showed an HPMC dispersed phase in the starch matrix and better water barrier properties, but they were more permeable to oxygen, especially when they contained citric acid (CA) as compatibilizer. CA induced cross-linking in the polymeric matrix, thus slightly increasing film hardness, but decreasing its extensibility. The incorporation of PCL in different ratios to starch films obtained by compression molding gave rise to polymer phase separation, although a small PCL miscibility in the starch rich phase was detected, which reduced the glass transition temperature of the starch phase. The structural heterogeneity and lack of interfacial adhesion between polymers gave rise to fragile films. Nevertheless, small amounts of PCL (10%) reinforced the matrix (increase in the elastic modulus). When the PCL ratio increased, WVP was reduced but oxygen permeability increased. The incorporation of CA as compatibilizer of these blends provoked an increase in the water solubility of the films, by hydrolysis, and improved the mechanical properties of the films when PCL ratio was low (10%), but it did not affect the film barrier properties. The incorporation of polyethylene glycol (PEG 4000) to the blends with a low proportion of PCL did not imply an improvement in the film properties, since it promoted phase separation. Starch-PCL blends with 1:0.05 mass ratio, without compatibilizer, were quite homogenous and exhibited good mechanical properties and stability. In order to incorporate greater amounts of PCL, thus improving film hydrophobicity and stability, PCL was chemically modified by grafting glycidyl methacrylate or glycidyl methacrylate and maleic anhydride (PCL-g), to be used as compatibilizers. Films with 20 % PCL and 2.5 or 5 % of PCL-g showed very good mechanical and barrier properties and stability, inhibiting starch retrogradation. Their barrier properties met the food packaging requirements for a wide number of food products. Bilayer films obtained by compression molding of starch (or starch with 5% PCL) and PCL layers showed very low WVP and oxygen permeability and adequate mechanical properties. The adhesion of bilayers was greatly improved by the application of ascorbic acid and, especially, potassium sorbate, as aqueous solutions, at the interface before compression molding. These compounds, in turn, imparted antioxidant and antimicrobial properties, respectively, to the films, thus improving their potential use as active packaging material for food uses. / [ES] Se han utilizado diversas estrategias para mejorar las propiedades físicas de films a base de almidón de maíz, con glicerol (30 %) como plastificante, basadas en el incremento de su carácter hidrofóbico, para reducir su sensibilidad al agua. El almidón se mezcló con diferentes compuestos (surfactantes y polímeros más hidrofóbicos), con y sin compatilizadores, para la obtención de films mixtos por diferentes técnicas de procesado (casting, mezclado en fundido, moldeo por compresión y extrusión). Se estudió también la formación de films bicapa almidón-poli-e-caprolactona (PCL) mediante moldeo por compresión. La adición de surfactantes a los films de almidón elaborados por casting dio lugar a una disminución de su permeabilidad al vapor de agua (WVP), pero aumentó su fragilidad. Los surfactantes con menor balance hidrófilo-lipófilo (HLB), y sólidos a temperatura ambiente, proporcionaron una microestructura de los films con menor tamaño de partícula, que potenció las propiedades barrera al vapor de agua. Por su mayor aplicabilidad industrial, se emplearon técnicas de termo-procesado para la obtención del resto de films estudiados. Los obtenidos por mezcla con hidroxipropil metilcelulosa (HPMC) presentaron una fase dispersa de HPMC en la matriz de almidón y mejores propiedades barrera al vapor de agua, pero fueron algo más permeables al oxígeno, sobre todo cuando se incorporó ácido cítrico (CA) como compatibilizador. Este provocó entrecruzamiento en la matriz polimérica, incrementado ligeramente su dureza y reduciendo su extensibilidad. La incorporación de PCL en diferentes proporciones a los films de almidón obtenidos por termo-compresión, dio lugar a la separación de fases polímericas, detectándose una pequeña miscibilidad de la PCL en la fase rica en almidón que redujo la temperatura de transición vítrea de la fase amilácea. La heterogeneidad de su estructura y la falta de adhesión entre fases dio lugar a films demasiado frágiles, aunque en pequeña proporción (10%), la PCL reforzó la matriz (aumentó el módulo de elasticidad). Al aumentar la proporción de PCL, disminuyó la WVP de los films, pero aumentó la permeabilidad al oxígeno. La incorporación de CA como compatibilizador de estas mezclas aumentó la solubilidad en agua de los films por efecto de hidrólisis y supuso una mejora en las propiedades mecánicas de los films con baja proporción de PCL (10 %), pero no afectó a sus propiedades barrera. La incorporación de polietilenglicol (PEG 4000) a las mezclas con baja proporción de PCL no mejoró las propiedades de los films, potenciando la separación de fases. Las mezclas almidón:PCL con proporción másica 1:0.05, sin compatibilizador, fueron bastante homogéneas y exhibieron buen comportamiento mecánico y estabilidad. Para incorporar una mayor proporción de PCL, y mejorar la hidrofobicidad y estabilidad de los films, se modificó la PCL por reacción con glicidil metacrilato o anhídrido maleico y glicidil metacrilato (PCL-g), para su uso como compatibilizadores. Los films con 20% de PCL y 2.5 y 5 % de los PCL-g presentaron muy buenas propiedades mecánicas y de barrera al vapor de agua y a los gases y buena estabilidad al inhibir la retrogradación del almidón. Sus propiedades de barrera cumplieron con los requisitos de envasado de un número importante de productos alimentarios. La obtención de films bicapa por termo-compresión a partir de almidón (o almidón con 5% PCL) y PCL proporcionó un material con muy baja permeabilidad al vapor de agua y al oxígeno y buenas propiedades mecánicas. La adhesión entre las capas mejoró en gran medida con la incorporación de ácido ascórbico, y sobre todo de sorbato potásico, en la interfase en forma de disolución acuosa antes de la termo-compresión. Estos compuestos impartieron, a su vez, propiedades antioxidantes y antimicrobianas, respectivamente, a los films, mejorando su uso potencial para el envasad / [CAT] S'han utilitzat diverses estratègies per a millorar les propietats físiques de films a base de midó de dacsa, amb glicerol (30 %) com plastificant, basades en l'increment del seu caràcter hidrofòbic, per a reduir la seua sensibilitat a l'aigüa. El midó es va mesclar amb diferents compostos (surfactants i polímers més hidrofòbics), amb i sense compatibilitzadors, per l'obtenció de films mixtos mitjançant diferents tècniques de processat (càsting, mesclat en fos, modelatge per compressió i extrusió). Es va estudiar també la formació de films bicapa midó-poli-e-caprolactona (PCL) mitjançant modelatge per compressió. L'addició de surfactants als films de midó elaborats per càsting va donar lloc a una disminució de la seua permeabilitat al vapor d'aigüa (WVP), però va augmentar la seua fragilitat. Els surfactants amb menor balanç hidròfil-lipòfil (HLB), i sòlids a temperatura ambient, varen proporcionar una microestructura dels films amb menor grandària de partícula, que varen potenciar les propietats barrera al vapor d'aigüa. Per la seua major aplicabilitat industrial, es van emprar tècniques de termo-processat per l'obtenció de la resta de films estudiats. Aquells obtinguts per mescla amb hidroxipropil-metilcellulosa (HPMC) varen presentar una fase dispersa de HPMC en la matriu de midó i millors propietats barrera al vapor d'aigüa, però varen ser un poc més permeables a l'oxigen, sobretot quan es va incorporar àcid cítric (CA) com compatibilitzador. Aquest va provocar entrecreuament en la matriu polimérica, incrementant lleugerament la seua duresa i reduïnt la seua extensibilitat. La incorporació de PCL en diferents proporcions als films de midó obtinguts per termo-compressió, va donar lloc a la separació de fases polimèriques, detectant-se una xicoteta miscibilitat de la PCL en la fase rica en midó que va reduir la temperatura de transició vítria de la fase amilàcea. L'heterogeneïtat de la seua estructura i la falta d'adhesió entre fases va donar lloc a films massa fràgils, encara que en xicoteta proporció (10%), la PCL va reforçar la matriu (augmentant el mòdul d'elasticitat). Al augmentar la proporció de PCL, va disminuir la WVP dels films, però va augmentar la permeabilitat a l'oxigen. La incorporació de CA com compatibilitzador d'aquestes mescles va augmentar la solubilitat en aigüa dels films per efecte d'hidròlisi i va suposar una millora en les propietats mecàniques dels films amb baixa proporció de PCL (10 %), però no va afectar les propietats barrera. La incorporació de polietilenglicol (PEG 4000) a les mescles amb baixa proporció de PCL no va millorar les propietats dels films, potenciant la separació de fases. Les mescles midó:PCL amb proporció màssica 1:0.05, sense compatibilitzador, varen ser prou homogènies i varen exhibir un bon comportament mecànic i una bona estabilitat. Per a incorporar una major proporció de PCL i millorar l'hidrofobicitat i estabilitat dels films, es va modificar la PCL per reacció amb glicidil metacrilat o anhídrid maleic i glicidil metacrilat (PCL-g), per al seu ús com compatibilitzadors. Els films amb 20% de PCL i 2.5 i 5 % dels PCL-g varen presentar molt bones propietats mecàniques i de barrera al vapor d'aigüa i als gasos i bona estabilitat al inhibir la retrogradació del midó. Les seues propietats de barrera varen complir amb els requisits d'envasament d'un nombre important de productes alimentaris. L'obtenció de films bicapa per termo-compressió a partir de midó (o midó amb 5% PCL) i PCL va proporcionar un material amb molt baixa permeabilitat al vapor d'aigüa i al oxigen i bones propietats mecàniques. L'adhesió entre les capes va millorar en gran mesura amb l'incorporació d'àcid ascòrbic, i sobretot de sorbat de potassi, en la interfase en forma de dissolució aquosa abans de la termocompressió. Aquestos compostos varen impartir, a la vegada, propietats antioxidants i antimicrobianes, respec / Ortega Toro, R. (2015). DESARROLLO Y CARACTERIZACION DE PELÍCULAS DE ALMIDÓN DE MAÍZ POR MEZCLADO CON COMPUESTOS MÁS HIDROFÓBICOS [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/52521 / TESIS

L’Hydroxypropyle méthylcellulose (HPMC) constitue un des polymères les plus utilisés pour la production de films destinés aux applications pharmaceutiques (gélules, comprimés, etc.). Afin de contrôler les propriétés physico-chimiques de films HPMC, des additifs sont fréquemment incorporés pendant la formulation du film: ce sont dans la plupart des cas un lubrifiant hydrophobe (acides gras) ou un plastifiant hydrophile (le polyéthylène glycol). L’objectif principal de ce travail est d’étudier les propriétés physico-chimiques en volume et en surface des films HPMC formulés aux échelles nanoscopique et macroscopique. Les propriétés volumiques concernent l’isotherme de sorption de l’eau, le taux de transmission de la vapeur d’eau, les propriétés thermiques et mécaniques des films. Les caractéristiques de surface ont été exploitées en termes de structuration, morphologie, séparation de phase, énergie de surface, adhésion et friction de films HPMC formulés. A l’échelle nanoscopique, la microscopie à force atomique en mode contact et en mode friction est un outil puissant pour étudier la nanoadhésion et la nanofriction. A l’échelle macroscopique, le test de tack et le tribomètre ont permis d’accéder aux propriétés d’adhésion et tribologiques. La présente étude souligne que les propriétés de films HPMC dépendent fortement de la nature et de la concentration de l’additif, et/ou de l’affinité avec l’eau. Elle montre aussi que la compatibilité HPMC-additif semble un facteur intéressant pour la variation des propriétés de surface de films HPMC formulés, et que la formulation est un moyen efficace pour contrôler les propriétés physico-chimiques de films à base de biopolymères. / Hydroxypropyl methylcellulose (HPMC) constitutes one of the most dedicated polymers used in the production of film coatings for pharmaceutical applications (capsules, tablets, etc.). In order to control the physicochemical properties of HPMC films, additives are frequently incorporated during film formulation: these are in most cases hydrophobic lubricant (like fatty acids) or hydrophilic plasticizer (like polyethylene glycol). The main objective of this work is to study the bulk and the surface physicochemical properties of HPMC formulated films at nanoscopic and macroscopic scales. Bulk properties include moisture sorption isotherms, barrier properties, thermal and mechanical properties. The surface characteristics have been explored in terms of structuration, surface morphologies, surface phase separation, surface energy, adhesion, and friction properties of HPMC-formulated films. At nanoscale, atomic force microscopy in contact mode and in friction mode is a powerful tool for studying nanoadhesion and nanofriction. At macroscale, tack test and pin-on-disk tribometer were conducted to access adhesion and tribological properties. The present study underlines the strong dependence of film properties on additive nature, concentration, and/or water sensitivity. It also shows that first the HPMC-additive compatibility seems to be an interesting factor behind the variation of surface properties of HPMC-formulated films, and second that formulation is an effective way to tune physicochemical properties of biopolymer-based films.

Twin screw wet granulation has been proved as a feasible alternative for traditional batch granulation process due to its continuous processing feature; considered as a significant processing method especially in the pharmaceutical industry. This thesis will explore the processibility of twin screw wet granulation with various formulations. The first section of the thesis focused on examining the processibility of wet granulation in a twin screw while using various grades of hydroxypropyl methylcellulose (HPMC) as an extended-release excipient. The method to find the processibility was by modifying the liquid-to-solid ratio for each formulation. The process window was defined by examining the amount of granules that fall in a pre-determined acceptable size range. This part focused on three substitution types of HPMC (Type 2910, Type 2208, and Type 2906) that varied in molecular weights. It was found that only Type 2910 HPMC showed a shift in the process window (also known as granulation range) in relation to the molecular weight of the formulations. A higher demand for binder liquid was found for higher molecular weight Type 2910 HPMC in order to form granules with acceptable sizes. The second part of this thesis was focused on understanding the process variables that might influence the processibility of the HPMC formulations. This part examined the impact of feed rate on the granulation range of Type 2910 HPMC specifically was examined. Multiple feed rates were tested, and it was found that the granulation range for lower molecular weight Type 2910 HPMC was easier to shrink when higher feed rates were applied. A transition in the granule formation method from liquid-bridging to compaction with respect to the feed rate was found for low molecular weight HPMC, whereas the high molecular weight HPMC always formed granules through compaction at all feed rates due to strong water retainability. / Thesis / Master of Applied Science (MASc)