Le présent travail montre la modélisation constitutive d'un géomatériau composé d'une matrice poreuse saturée et déformable contenant une distribution périodique de fissures évolutives remplies de fluide. La méthode d'homogénéisation des développements asymptotiques est utilisée afin de déduire un modèle capable de décrire le couplage hydro-mécanique macroscopique. Prenant en considération l'évolution de fissures et sans faire des hypothèses phénoménologiques, une analyse énergétique mésoscopique couplé avec un schéma d'homogénéisation a été développée et elle fournit une loi d'évolution d'endommagement macroscopique. De cette façon, un lien direct entre les phénomènes de rupture de la structure mésoscopique et l'endommagement macroscopique correspondant est établie. Finalement, on présente une étude numérique du comportement macroscopique d'endommagement hydro-mécanique. / This work presents the constitutive modeling of a geomaterial consisting of a deformableand saturated porous matrix including a periodic distribution of evolving fluid-filledcavities. The homogenization method based on two-scale asymptotic developments isused in order to deduce a model able to describe the macroscopic hydro-mechanicalcoupling. By taking into account the cavity growth and without any phenomenologicalassumption, it is proposed a mesoscopic energy analysis coupled with the homogenizationscheme which provides a damage evolution law. In this way, a direct link between themeso-structural fracture phenomena and the corresponding macroscopic damage isestablished. Lastly, a numerical study of the local macroscopic hydro-mechanical damage behaviour is presented. / In questa tesi si presenta la modellazione costitutiva di un geomateriale composto da unamatrice porosa satura e deformabile contenente una distribuzione periodica di cavitàriempite da fluido che si propagano. Il metodo di omogeneizzazione basato sugli sviluppiasintotici a doppia scala viene utilizzato con l'obiettivo di dedurre un modello capace didescrivere l'accoppiamento idro-meccanico macroscopico. Prendendo in considerazione lapropagazione delle cavità e senza nessuna ipotesi fenomenologica, si propone un'analisienergetica mesoscopica accoppiata ad uno schema di omogeneizzazione che fornisce unalegge di evoluzione del danno.In questo modo, una relazione diretta tra i fenomeni difrattura meso-strutturali ed il corrispondente danno macroscopico viene stabilita. Infine,uno studio numerico del comportamento macroscopico locale di danno idro-meccanico viene presentato.

Cette thèse présente une étude expérimentale et numérique d'essais de chute libre et de vibrations aléatoires d'emballages en carton ondulé contenant différents calages en mousse. Un modèle d'homogénéisation efficace pour le carton ondulé a été développé. Dans ce modèle homogénéisé, le carton ondulé est représenté par une plaque 2D. Au lieu d'utiliser une loi de comportement locale (reliant les déformations aux contraintes) à chaque point d'intégration, l'homogénéisation conduit aux rigidités globales (reliant les déformations généralisées aux forces résultantes) pour la plaque équivalente homogène. Ce modèle a été implémenté dans le logiciel Abaqus. Le comportement de la mousse a été déterminé expérimentalement et modélisé avec un modèle de mousse déformable d'Abaqus. Les emballages sont soumis à des tests de chute libre d'une hauteur donnée sur un sol rigide et des essais de vibrations aléatoires type bruit blanc sur table vibrante. Les résultats numériques obtenus en utilisant la simulation avec le modèle homogénéisé concordent bien avec les résultats expérimentaux. Nous avons également montré que la contribution de la caisse en carton ondulé à la réponse au choc et à la vibration aléatoire ne pouvait pas être négligée dans la conception des calages. / This thesis presents experimental and numerical studies of drop tests random vibrations of corrugated cardboard packaging containing different foam cushions. An efficient homogenization model for the corrugated cardboard has been developed. In this homogenized model, the corrugated cardboard is represented by a 2D plate. Instead of using a local constitutive law (relating the strains to the stresses) at each material point, the homogenization leads to global rigidities (relating the generalized strains to the resultant forces) for the equivalent homogeneous plate. This model was implemented into the FE software Abaqus. The foam behaviour was experimentally determined and modelled using a crushable foam model of Abaqus. The packages are tested in free fall from a given height on a rigid floor and submitted to white noise random vibrations. The numerical results obtained using the FE simulation with the homogenized model agree well with the experimental results. We have also shown that the contribution of the corrugated cardboard box to the shock and random vibration responses could not be neglected in the design of cushioning package.

Le présent travail a pour objectif de comprendre l’influence des paramètres géométriques des éco-matériaux d’enveloppe, tels que le béton de chanvre, sur les mécanismes de transferts couplés de chaleur, d'air et d’humidité afin de prédire le comportement du bâtiment dans le but de le piloter et de l’améliorer dans sa durabilité. Pour cela, une approche multi-échelle est mise en place. Elle consiste à maîtriser les phénomènes physiques dominants et leurs interactions à l’échelle microscopique. S’ensuit, une modélisation à double échelle, microscopique–macroscopique, des transferts couplés de chaleur, d’air et d’humidité qui prend en compte les propriétés intrinsèques et la topologie microstructurale du matériau moyennant le recours à la tomographie rayon X conjuguée à la corrélation d’images 2D et 3D. Pour cela, une campagne de caractérisation fine des propriétés physiques et hygrothermiques du béton de chanvre confectionné au laboratoire a été réalisée. Elle s’est focalisée sur l’étude de l’impact du vieillissement, l’état thermique et hydrique du matériau sur ses propriétés intrinsèques. Les résultats montrent une excellente capacité d'isolation thermique et de régulation naturelle d’humidité du béton de chanvre. Puis, une caractérisation microscopique par différentes techniques d’imagerie a été effectuée. Les reconstructions 3D du matériau réel scanné au tomographe aux rayons X à différentes résolutions montrent que le béton de chanvre possède plusieurs échelles de porosité, allant de la microporosité au sein du liant et des chènevottes à la macroporosité inter-particulaire. Le comportement hygro-morphique sous sollicitations hydriques a été ensuite étudié. Les résultats de la corrélation d’image numérique 2D et de la tomographie aux rayons X couplés à la corrélation d’images volumiques, montrent la nature du comportement du béton de chanvre soumis à des hygrométries différentes. En effet, la chènevotte subit des déformations plus importantes que le liant, causant ainsi des modifications de la microstructure du matériau. Sur le volet de la modélisation, moyennant la technique d’homogénéisation périodique un modèle des transferts couplés de chaleur, d’air et d’humidité dans les matériaux poreux de construction a été développé. Les tenseurs de diffusion et de conductivité thermique homogénéisés ont été calculés numériquement. Ensuite, une confrontation entre les résultats du calcul des coefficients de diffusion macroscopique et ceux expérimentaux obtenus au LaSIE a été réalisée. Elle met en évidence la qualité de la prédiction. De plus, la conductivité thermique de la phase solide a été ainsi déduite. Les résultats obtenus dans le cadre de ce travail de thèse ont mis en exergue l’influence de l’état hydrique et thermique du béton de chanvre sur ces propriétés intrinsèques, et sa microstructure très hétérogène. Ils ont révélé aussi les limites des approches phénoménologiques basées sur l’établissement des bilans de masse, de quantité de mouvement et d’énergie. / The aim of this work is to understand the influence of the geometric parameters of envelope eco-materials, such as hemp concrete, on the mechanisms of coupled heat, air and moisture transfers, in order to predict behavior of the building to control and improving it in its durability. For this a multi-scale approach is implemented. It consists of mastering the dominant physical phenomena and their interactions on the microscopic scale. Followed by a dual-scale modeling, microscopic-macroscopic, of coupled heat, air and moisture transfers that takes into account the intrinsic properties and microstructural topology of the material using X-ray tomography combined with the correlation of 2D and 3D images. A characterization campaign of physical and hydrothermal properties of the hemp concrete manufactured in the laboratory was carried. It focused on studying the impact of aging, thermal and hydric state of the material on these intrinsic properties. The results show an excellent thermal insulation and natural moisture regulation capacity of hemp concrete. Then, a microscopic characterization by different imaging techniques was performed. The 3D reconstructions of the real material scanned with X-ray tomography at different resolutions show that hemp concrete has several scales of porosity, ranging from micro-porosity within the binder and hemp shiv to the inter-particle macro-porosity. The hydromorphic behavior under hydric solicitations was studied. The results of the 2D digital image correlation and X-ray tomography coupled with the volumetric image correlation show the nature of the behavior of hemp concrete subjected to different relative humidities. In fact, the hemp shiv undergoes greater deformations than the binder, thus causing changes in the microstructure of the material. On the modeling part, a model of coupled heat, air and moisture transfer in porous building materials was developed using the periodic homogenization technique. The homogenized tensors of diffusion and thermal conductivity were determined numerically. Then, a confrontation between the results of the calculation of the macroscopic diffusion coefficients and the experimental results obtained at the LaSIE was carried out. It highlights the quality of the prediction. In addition, the thermal conductivity of the solid phase was thus deduced. The results obtained in the framework of this PhD thesis have highlighted the influence of the hydric and thermal state of the hemp concrete on these intrinsic properties and its very heterogeneous microstructure. They also revealed the limitations of phenomenological approaches based on the establishment of the balances of mass, amount of motion and energy

Ce travail s'inscrit dans le contexte des techniques de renforcement des sols, permettant d'améliorer les performances mécaniques de terrains de qualité médiocre. Parmi ces techniques, l'utilisation d'inclusions souples prenant la forme de colonnes ou de tranchées croisées connaît une diffusion croissante. Même si les aspects relatifs à leur procédé de construction sont aujourd'hui bien maîtrisés, les méthodes de dimensionnement de ces ouvrages en sols renforcés restent à améliorer. Dans cette thèse, nous proposons d'utiliser la méthode d'homogénéisation afin d'analyser le comportement global des ouvrages en sols renforcés, dans le cadre de la théorie de l'élasticité (propriétés de rigidité) aussi bien que dans celle du calcul à la rupture (propriétés de résistance). Tenant compte de la périodicité géométrique des différentes configurations de renforcement, nous déterminons le comportement des sols renforcés tout d'abord au niveau local puis à l'échelle de l'ouvrage. Pour évaluer les capacités de résistance des ouvrages en sols renforcés, les approches statique et cinématique du calcul à la rupture sont mises en œuvre analytiquement ou numériquement selon la nature du matériau de renforcement utilisé. Par des formulations numériques innovantes adaptées à cette théorie, nous parvenons notamment à évaluer les domaines de résistance macroscopiques des sols renforcés par colonnes ou tranchées croisées, qui peuvent ensuite être pris en compte dans le comportement à la rupture des ouvrages en sols renforcés. Deux exemples d'application de cette procédure, relatifs au problème de capacité portante d'une semelle de fondation reposant sur un sol renforcé d'une part et à l'analyse de la stabilité d'un remblai d'autre part, sont effectués / This work takes place in the context of soil reinforcement techniques, aimed at improving the mechanical performances of poor quality grounds. Among these techniques, the use of soft inclusions taking the form of columns or cross trenches has known important developments. Even if the aspects relative to their construction process are presently well mastered, the design methods of such reinforced soil structures still remain to be greatly improved. The present work advocates the use of the homogenization method for assessing the global behavior of reinforced soil structures, both in the context of linear elasticity (stiffness properties) and in the framework of yield design (strength properties). Taking into account the geometrical periodicity of the various reinforcement configurations, we thus determine the behavior of the reinforced soils first locally and then at the global scale. To assess the strength capacities of reinforced soil structures, the static and kinematic approaches of the yield design theory are performed analytically or numerically depending on the kind of reinforcing material which is used. Adopting innovative numerical formulations dedicated to this theory, we can notably evaluate the macroscopic strength domains of column as well as cross trench reinforced soils which can then be introduced in the yield design of reinforced soil structures. Two illustrative applications of this procedure are performed relating to the bearing capacity problem of a reinforced soil shallow foundation on the one hand, the stability analysis of an embankment on the other hand

L’os est un matériau vivant avec une structure hiérarchique complexe qui lui confère des propriétés mécaniques remarquables. L’os subit perpétuellement des contraintes mécaniques et physiologiques, ainsi sa qualité et sa résistance à la fracture évoluent constamment au cours du temps à travers le processus de remodelage osseux. La qualité osseuse est non seulement définie par la densité minérale osseuse mais également par les propriétés mécaniques ainsi que la microarchitecture. Dans le cadre de la présente thèse, on a développé une modélisation multiéchelle unifiée couplant à la fois les activités cellulaires au comportement mécanique de l'os tenant compte des différents niveaux hiérarchiques de l'os: de l’ultrastructure au remodelage osseux. Ce modèle permet d’étudier le comportement mécano-bibliologique de l’os et de prédire ses propriétés mécaniques apparentes à différentes échelles allant du nanoscopique au macroscopique en fonction des constituants élémentaires de l'os. Pour atteindre cet objectif, une démarche en quatre phases a été adoptée. La première phase consiste à décrire les constituants élémentaires de l’os. La deuxième phase avait pour objectif la modélisation multiéchelle de l'ultrastructure osseuse constituée de trois échelles nanoscopiques (microfibrille, fibrille et fibre) par la méthode des éléments finis et des réseaux de neurones. La troisième phase correspond à la modélisation des échelles micro-macroscopiques de l’os cortical (lamelle, ostéon, os cortical) en utilisant comme paramètres d’entrée les propriétés de la fibre déterminées dans la deuxième phase. Enfin, dans la dernière phase, on a développé un modèle mécano-biologique du remodelage osseux permettant de simuler le processus d'adaptation osseuse tenant compte explicitement des activités biologiques des cellules osseuses. Les propriétés mécaniques prédites par nos algorithmes multiéchelles ont servi pour alimenter le modèle de remodelage. Ce modèle a été implémenté au code de calcul d’éléments finis ABAQUS/Standard à travers sa routine utilisateur UMAT. Finalement, le modèle EF mécano-biologique multiéchelle du remodelage osseux a été appliqué pour simuler différents scénarii de remodelage sur des fémurs humains (2D et 3D). Différents facteurs ont été ainsi analysés tels que l'âge, le genre, l'amplitude des activités physiques, etc. Les résultats obtenus sont conformes (qualitativement) avec les observations cliniques et cohérents avec les différentes études expérimentales. En conclusion: (i) Les modèles unifiés ainsi développés (modèle multiéchelle, modèle mécano-biologique de remodelage osseux) contribuent à l'analyse fine du comportement de l'os humain. (ii) L'application des algorithmes a permis d'effectuer des essais virtuels pour analyser les effets combinés de nombreux facteurs caractérisant la qualité osseuse. / Bone is a living material with a complex hierarchical structure which entails exceptional mechanical properties. Bone undergoes permanent mechanical and physiological stresses, thus its quality and fracture toughness are constantly evolving over time through the process of bone remodeling. Bone quality is not only defined by bone mineral density but also by the mechanical properties and microarchitecture. The current thesis offers a multiscale modeling approach unifying the cell activity to the mechanical behavior, taking into consideration the hierarchical levels of bone, from the ultrastructure to bone remodeling. This model permits to study the mechanobiological behavior and to predict the mechanical properties of the bone at different scales from nano to macro depending on the elementary constituents of bone. To achieve the objective of the current work, an approach of four phases was adopted. The first phase is to describe the basic components of the bone. The second phase concerns the multiscale modeling of the three nanoscopic levels of bone ultrastructure (microfibril, fibril and fiber) by the finite element method and neural networks. The third phase aims to model the micro-macroscopic structures of cortical bone (lamella, osteon, cortical bone) using the fiber properties predicted from the second phase as input parameters. In the last phase, a mechano-biological model of bone remodeling was achieved to simulate the process of bone adaptation explicitly considering the biological activities of bone cells. Mechanical properties predicted by our multiscale algorithms were used to feed the remodeling model. This model has been implemented into the ABAQUS/Standard finite elements code as a user subroutine. Finally, the finite element mechano-biological multiscale model of bone remodeling was applied to simulate different scenarios on human femurs (2D and 3D). Hence, different factors such as: age, gender, physical activities, etc were analyzed. The obtained results are conformed (qualitatively) to clinical observations and consistent with the various experimental studies. In summary, (i) the models portrayed here (multiscale model, mechanical-biological model of bone remodeling) contribute by their unified approach to the realistic modeling of the response of human bone. (ii) The application of the algorithms permits to perform virtual experiments to scrutinize the combined effects of numerous factors dictating the bone quality.

En raison de l'exigence de protection de l'environnement, les briques d'argile cuites sont face à une nouvelle tendance de développement. Briques d'argile cuites ne sont pas seulement satisfaits de la mécanique force mais aussi augmentation de l'utilisation de l'énergie. La conductivité thermique est un paramètre très important mesurer l'utilisation de l'énergie. Sur le principe de garantir essentiellement propriétés mécaniques, la réduction de la conductivité thermique a été l'un des développements importants objectifs dans l'industrie du bâtiment.Basé sur l'analyse de la microstructure, les pores microscopiques ont un effet sur la macroscopie constantes élastiques et conductivité thermique. Micropores parallèles résultant de la production les méthodes provoquent l'isotropie transversale des briques d'argile cuites. Cependant, ce n'est pas clair que l'influence des micropores sur les propriétés macroscopiques. Bien que certains modèles étudié l'effet de la porosité sur les propriétés mécaniques des briques d'argile cuite, ces modèles sont empiriques et ont ignoré de nombreuses informations microscopiques. Un des buts de la thèse est d'analyser l'influence de la forme, l'orientation et la distribution spatiale de microscopique facteurs sur les propriétés mécaniques et la conductivité thermique afin de fournir une référence optimiser la micro-structure des briques d'argile cuites. / Due to the environmental protection requirement, fired clay bricks are facing new development tendency. Fired clay bricks are not only satisfied with mechanical strength but also rising energy utilization. Thermal conductivity is a very important parameter to measure the energy utilization. On the premise of guaranteeing the basically mechanical properties, reducing thermal conductivity has been one of important development goals in building industry.Based on the analysis of micro-structure, microscopic pores have an effect on macroscopic elastic constants and thermal conductivity. Parallel micropores resulting from producing methods cause the transverse isotropy of fired clay bricks. However, it is not clear that the influence of micropores on the macroscopic properties. Though some models studied the effect of porosity on mechanical properties of fired clay bricks, these models are empirical and ignored many microscopic information. One of the goals of the thesis is to analyze the influence of shape, orientation and spatial distribution of microscopic factors on mechanical properties and thermal conductivity in order to provide a reference to optimize the micro-structure of fired clay bricks.

O objetivo do presente trabalho foi desenvolver e validar um método analítico empregando microextração em fase sólida (SPME) para detecção e quantificação de isoflurano (ISO) na forma volátil e incluso em nanoemulsões intravenosas e, ainda, avaliar o efeito biológico destas. A detecção do ISO foi realizada através de cromatografia em fase gasosa com detector de ionização de chama (CG/DIC). As condições ideais para realização da pré-concentração e extração de ISO através da técnica de SPME foram temperatura ambiente, agitação constante, 30 min de extração e 2 min de dessorção no injetor do CG. O método desenvolvido foi validado avaliando os parâmetros de especificidade, linearidade, limites de detecção e quantificação, precisão, exatidão e robustez. As nanoemulsões contendo ISO foram desenvolvidas através da homogeneização à alta pressão, e apresentaram diâmetro médio, índice de polidispersão, potencial zeta e pH de 150 ± 0,78 nm, 0,08 ± 0,01, - 18 ± 2,4 mV e 6,03 ± 0,04, respectivamente. O pH foi ajustado para 7,4 (valor fisiológico). O teor de ISO nas formulações foi de 98,4 %. Não houve modificação das características físico-químicas das nanoemulsões após 30 dias de armazenamento a 8 ºC. Análises de espalhamento de luz múltiplo não demonstraram tendência a fenômenos de instabilidade física para as formulações. Os estudos do efeito anestésico das nanoemulsões intravenosas contendo ISO em cães evidenciaram uma redução significativa (p < 0,05) na dose comparada com a administração de ISO volátil. Não houve alterações no débito cardíaco, saturação de oxigênio na hemoglobina e nos biomarcadores das funções renal, hepática e muscular. Uma queda na pressão arterial dos cães foi observada em todos os tratamentos devido ao efeito hipotensor do ISO. Após administração das nanoemulsões contendo ISO e branca, observou-se taquipnéia, edema, eritema, e baixas concentrações de dióxido de carbono expiradas. Assim, a nanoemulsificação do ISO foi realizada com sucesso e a aplicação na anestesia geral intravenosa foi demonstrada. / The aims of this work were to develop and validate an analytical method using solidphase microextraction (SPME) to detect and quantify isoflurane (ISO) inhalation liquid and loaded in intravenous nanoemulsions, and also evaluate the biological effect of the formulations. ISO detection was made by gas chromatography with flame ionization detector (GC/FID). The ideal conditions setting for the pre concentration and extraction of ISO through SPME were environmental temperature, constant stirring, 30 min for extraction and 2 min for analyte desorption in the GC inlet port. The developed method was validated by means of specificity, linearity, detection and quantification limits, precision, accuracy and robustness. The ISOloaded nanoemulsions were formulated by high-pressure homogenization, and presented average diameter, polydispersity index, zeta potential and pH of 150 ± 0.78 nm, 0.08 ± 0.01, -18 ± 2.4 mV and 6.03 ± 0.04, respectively. The pH was adjusted to 7.4 (physiological value). The drug content on the formulations was 98.4 %. After 30 days of storage at 8 ºC no changes on nanoemulsion’s physicalchemical characteristics were observed. Multiple light scattering analysis did not demonstrate any physical destabilization phenomena for the formulations. The anesthetic effect study for the intravenous ISO-loaded nanoemulsions in dogs highlighted a significant reduction (p < 0.05) in dosage regimen when compared to the volatile ISO administration. There were no alterations on cardiac rate, oxygen hemoglobin saturation and on biomarkers of the renal, hepatic and muscle functionalities. A decrease in dog’s arterial blood pressure in all treatments due the hypotensive effect caused by ISO was observed. After the administration of the nanomulsions, ISO-loaded and unloaded, occurred tachypnea, edema, erythema and low end tidal concentrations of carbon dioxide. Taking all above into account, the method was considered easy on execution and suitable for laboratory routines, the ISO nanoemulsification was made successfully and its application on general anesthesia was demonstrated.

L’objectif de cette étude est de modéliser la digestion dans l’intestin grêle : le transport des aliments par les ondes péristaltiques, la dégradation par les enzymes endogènes et exogènes et l’absorption active et passive. Un modèle mécaniste basé sur les équations différentielles ordinaires a été utilisé pour représenter la digestion. Les équations décrivent l’évolution de la position et de la composition du bolus provenant de l’estomac. Nous montrons ensuite par les méthodes d’homogénéisation mathématiques que ce modèle peut être considéré comme une version macroscopique des modèles plus réalistes, qui contiennent des phénomènes biologiques à des échelles inférieures de l’intestin grêle. Enfin, nous étudions l’influence du changement de la structure de bolus sur la digestion en intégrant les fibres alimentaires dans sa composition. Les deux principales caractéristiques des fibres alimentaires qui interagissent avec la fonction de l’intestin grêle, à savoir, la viscosité et la capacité de rétention d’eau ont été modélisées. / The purpose of this study is to model the digestion in the small intestine : transport of the the bolus by the peristaltic waves, feedstuffs degradation according to the endogenous and exogenous enzymes and nutrients absorption. A mechanistic model based on ordinary differential equations is used to represent the digestion. The equations describe the evolution of the position and composition of the bolus of feedstuffs coming from the stomach. We prove by using the homogenization methods, that this model can be considered as a macroscopic version of more realistic models which contain the biological phenomena at lower scales of the small intestine. Finally, we investigate the digestion of a non-homogeneous feedstuffs matrix by integrating the dietary fibre in the bolus. The two main physiochemical characteristics of dietary fibre which interact with the function of the small intestine, i.e. viscosity and water holding capacity are modelled.

Estudos in vitro de absorção percutânea são uma importante ferramenta para avaliação de formulações semissólidas e transdérmicas. Embora haja um grande número de agências reguladoras preocupadas com a harmonização metodológica, em muitos parâmetros elas permanecem flexíveis e isto é possível verificar na ampla variedade e divergências encontradas na literatura. O objetivo do trabalho foi avaliar parâmetros ainda flexíveis a respeito dos estudos in vitro como modo de separação das camadas da pele, permeabilidade da pele congelada (tempo de armazenamento) e diferença de permeabilidade dos locais anatômicos. Os estudos foram conduzidos utilizando células de Franz, pele suína como membrana e formulações (comercializada e inovadora) contendo penciclovir. Inicialmente, nanoemulsões foram preparadas utilizando técnica de homogeneização a alta pressão, caracterizadas, incorporadas em gel de carbômero 940 e avaliadas quanto à liberação tópica em pele suína. Simultaneamente ao desenvolvimento da formulação foi desenvolvido e validado método analítico para quantificação do fármaco nas formulações e nas camadas da pele suína. As nanoemulsões apresentaram-se monodispersas com diâmetro de gotícula em torno de 180-200 nm, potencial zeta de -27 mV e teor de penciclovir de 98% mantendo sua estrutura após a incorporação em carbômero 940. A metodologia analítica demonstrou ter alta sensibilidade (LoQ 0,05 μg/mL), especificidade e uma adequada recuperação do fármaco a partir das matrizes biológicas (90 – 104%). Quanto aos estudos in vitro de comparação de metodologias, foi possível observar que, dependendo da solubilidade do fármaco em água e das características da formulação, o método clássico de separação das camadas da pele por imersão em água não é o mais indicado. Já para permeabilidade da pele suína congelada, os resultados obtidos indicam um aumento significativo na penetrabilidade e permeabilidade após um mês de congelamento. Dentre os locais anatômicos testados, não houve diferença entre abdômen e orelha suína desde que obtidos antes do procedimento de escaldo. / In vitro percutaneous absorption studies are an important tool for evaluation of semisolid and transdermal formulations. Although there are a large number of official guides concerned with methodological harmonization in many parameters they remain flexible and it is possible to see the wide variety and differences reported in the literature. The aim of study was to evaluate some parameters regarding the in vitro studies as the mode of skin layers separation, skin frozen stability and permeability difference of anatomical sites. These studies were conducted with porcine skin and formulations (conventional and novel) using penciclovir as model drug. Initially, nanoemulsions were prepared using high pressure homogenization, characterized and incorporated into carbomer 940 gel and evaluated for topical delivery using porcine skin. Simultaneously with the development of the formulation, analytical method for quantification of the drug in the formulations and porcine skin layers was developed and validated. The nanoemulsions presented themselves monodisperse with droplet diameter of 180-200 nm, zeta potential of about -27 mV and penciclovir content of 98% maintaining their structure after incorporation into carbomer 940. The analytical methodology was shown to have high sensitivity (LOQ 0.05 μg/mL), specificity and adequate recovery of drug from the biological matrices (90-104%). Regarding the in vitro comparison methodologies, it was observed that, depending on the solubility of the drug in water and the characteristics of the formulation, the classical separation is not the most suitable for separation of the skin layers. For the stability of frozen porcine skin, the results indicate a significant increase in permeability and penetrability after one month of freezing. Within the anatomical sites tested, there was no difference between the abdomen and ear porcine skin since obtained before the scald procedure.

Em virtude da necessidade de novas obras de infraestruturas, por muitas vezes, em locais onde o solo não atendia às necessidades básicas exigidas por elas, originam-se problemas de ordem geotécnica, os quais foram resolvidos por meio de misturas solo-cimento. O presente trabalho teve como objetivo o estudo de propriedades mecânicas e elásticas de misturas de areia e cimento, sendo este dividido em duas abordagens: experimental e micromecânica. Para a execução da abordagem experimental, além da execução de ensaios de resistência a compressão simples e medidas de parâmetros de rigidez ao longo do tempo, foi desenvolvido um minicone e também uma câmara triaxial de grandes proporções com os quais foram executados ensaios. A abordagem micromecânica foi realizada através da aplicação da teoria da homogeneização. Para avaliar as propriedades elásticas do compósito foram utilizados os modelos Mori-Tanaka e Auto-Consistente, enquanto que a obtenção da resistência homogeneizada foi baseada na teoria do estado limite. Os ensaios experimentais demostraram que os módulos medidos e a resistência à compressão simples possuem comportamentos semelhantes em relação ao aumento de sua magnitude. Os ensaios de prospecção do minicone demostraram que a tensão de confinamento influencia até corpos de prova cimentados. Ainda foram observadas relações entre o módulo de cisalhamento, a resistência à compressão simples e a resistência média de ponta. Os resultados obtidos através da abordagem micromecânica, quando confrontados com os resultados experimentais, apresentaram diferenças irrelevantes tanto para a resistência quanto para os módulos. Baseados nos resultados obtidos através desse trabalho concluiu-se que o comportamento das misturas areias-cimento é regido pelo índice oriundo da razão entre a porosidade e a quantidade volumétrica de cimento. Também foi comprovado o potencial da micromecânica como ferramenta de modelagem de misturas areia-cimento. / The necessity of new infrastructure earthworks in areas where the soil does not present the required mechanical properties originates problems of geotechnical order. These problems can be solved through the improvement of mechanical characteristics of the materials by reducing porosity through compaction, as well as the addition of cementitious materials such as Portland cement. This research aimed to evaluate the mechanical properties of sand-cement mixtures through two approaches: experimental and micromechanics. In the experimental approach were carried out unconfined compression tests and bender elements measurements over time in sand-cement specimens varying the porosity and the cement content. Furthermore, a mini-cone (MCPT) and a triaxial chamber of large proportions were developed, in which MCPT tests have been carried out under distinct confining pressures and distinctive sand-cement mixtures. In these tests, the variation of porosity and cement content was evaluated. The experimental results were analyzed from the perspective of the recently developed porosity-cement index. The results have shown that the porosity-cement index controls the mechanical properties of sand-cement mixtures from very small strains to failure. The micromechanical approach was performed by the theory of homogenization. To evaluate the elastic properties of the sand-cement composite, the Mori-Tanaka and self-consistent models were used, while the homogenized shear strength was obtained based on the limit state theory. The results obtained by the micromechanical approach, when compared with the experimental results, showed irrelevant differences to both strength and stiffness.