FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Grande parte do petrÃleo nacional encontra-se em ambiente offshore, onde suas condiÃÃes de extraÃÃo apresentam nÃveis crÃticos de tensÃo e um alto potencial corrosivo. Um dos grandes desafios do setor à assegurar as propriedades de juntas submarinas de aÃos soldadas quanto à resistÃncia mecÃnica, tenacidade e dureza, onde as mesmas, expostas a proteÃÃo catÃdica, podem sofrer fragilizaÃÃo por hidrogÃnio. Com o objetivo de evitar a necessidade de tratamento tÃrmico pÃs-soldagem no amanteigamento das juntas, uma alternativa à o emprego da tÃcnica dupla camada, a qual por meio da relaÃÃo adequada de energia de soldagem da primeira e segunda camada, visa-se obter o revenimento e o refino da estrutura com a sobreposiÃÃo de ciclos tÃrmicos. Para selecionar os parÃmetros utilizados nas camadas foram realizados os Testes Higuchi, depositando a liga de nÃquel UNS N06625 no aÃo baixa liga alta resistÃncia AISI 8630M com o processo de soldagem plasma com arco transferido, empregando material de adiÃÃo na forma de pà (PTA). As soldagens foram realizadas variando-se a energia de soldagem, a tÃcnica de soldagem e o gÃs de proteÃÃo. A partir das extensÃes de zona dura (ZD), zona macia (ZM), regiÃo grÃo grosso (ZACGG) e regiÃo grÃo fino (ZACGF) da zona afetada pelo calor obtidas com realizaÃÃo de perfis de microdureza e microscopia Ãtica, foi encontrada uma melhor relaÃÃo de energia, que promovesse o revenimento e o refino da microestrutura da ZAC. Juntas dos aÃos AISI 8630M e ASTM A182 F22 foram amanteigadas com as relaÃÃes de energia obtidas utilizando o processo PTA e enchidas utilizando o processo MIG. Nas interfaces dissimilares geradas entre os aÃos baixa liga alta resistÃncia e a liga de nÃquel UNS N06625 do amanteigamento foi realizada caracterizaÃÃo microestrutural e suas propriedades mecÃnicas foram medidas com a realizaÃÃo de microdureza, dureza e ensaio de fratura, visando avaliar a eficiÃncia dos Testes Higuchi. TambÃm foram analisadas a interface gerada entre a liga de nÃquel na forma de pà (amanteigamento) e na forma de arame (enchimento da junta) com microscopia Ãtica e dureza. As juntas amanteigadas na condiÃÃo indicada pelos testes Higuchi apresentaram um intenso refino na ZAC do aÃo baixa liga. A interface dissimilar apresentou uma composiÃÃo quÃmica intermediÃria entre os aÃos utilizados e a liga de nÃquel. A zona afetada pelo calor (ZAC) das amostras amanteigadas apresentaram uma diminuiÃÃo nos valores de dureza, no entanto para ambos os aÃos esses valores foram superiores aos estabelecidos pelas normas que regem a sua aplicaÃÃo. Os ensaios de fratura indicam que o fator de intensidade de tensÃo (K) encontrado para as amostras amanteigadas foram condizentes com a literatura. / Much of the domestic oil is located offshore environment where their extraction conditions have critical levels of strain and a high corrosion potential. One of the major challenges the sector is to ensure the properties of underwater joints welded steel as the mechanical strength, toughness and hardness, where the same exposed to cathodic protection can suffer hydrogen embrittlement. With the aim of avoiding the need for post-welding heat treatment of the buttering joints, an alternative is the use of double layer technique, which by means of suitable welding power ratio of the first and second layer, the aim is to obtain the tempering and refining structure with overlapping thermal cycles. To select the parameters used in the tests Higuchi layers were carried out by depositing nickel alloy UNS N06625 in high strength low alloy steel AISI 8630M with the process of welding plasma transferred arc, employing filler metal in powder form (PTA). The weldments were performed varying the welding energy, the welding technique and the shielding gas. From extensions harsh zone (HZ), soft zone (SZ), rough grain region (HAZRG) and fine grain region (HAZFG) of the heat affected zone obtained by performing microhardness and optical microscopy, better energy ratio was found, which promotes tempering and refining the microstructure of HAZ. Joints of AISI 8630M and ASTM A182 F22 were buttery with energy ratios obtained using the PTA process and filled using the MIG process. In the dissimilar interfaces generated between the low alloy high strength steels and nickel alloy UNS N06625 buttering the microstructural characterization was performed, and their mechanical properties were measured by carrying out hardness, hardness and fracture test, to evaluate the efficiency of tests Higuchi. The generated interface between the nickel alloy in powder form (buttering) and in the form of wire (joint filler) were anayzed using optical microscopy and hardness tests. The buttery joints in the condition indicated by Higuchi tests showed an intense refining HAZ of the low alloy steel. The dissimilar interface had a chemical composition intermediate between the steel used and nickel alloy. The heat affected zone (HAZ) of buttery showed a decrease in hardness, however for both steels these values of hardness test were higher than those established by the rules governing its application. The fracture test indicate that the fracture stress intensity factor (K) found for the buttery samples were consistent with the literature.

Atualmente, há a necessidade de se desenvolver aços com alta resistência à propagação de trincas, especialmente em condições de carregamentos cíclicos, ou seja, resistentes à fadiga, na qual sua aplicabilidade se da em função de suas propriedades mecânicas. No presente trabalho estudou-se o efeito do preaquecimento na zona afetada pelo calor do aço AISI/SAE 4130 com composição química modificada, com altos teores de Mo, comparando as propriedades mecânicas e microestruturais nas condições como soldada, tratada termicamente e aplicando a técnica de Metodologia do Preaquecimento Combinado (MPC) com otimização de ciclos térmicos através da combinação do preaquecimento entre o 1º e 3º passe da 1º e 2º camada, respectivamente. A fim de avaliar as propriedades mecânicas, foram realizados ensaios de microdureza, mapeamento de dureza e ensaio de tenacidade ao impacto charpy. Para análise microestrutural, foi realizado microscopia ótica e microscópio eletrônico de varredura (MEV) para analisar as regiões de grãos grosseiros, fino e as intersecções entre as regiões da Zona Afetada pelo Calor (ZAC), quando aplicado o MPC. Como resultado, observa-se que preaquecimento é uma forma efetiva de redução de dureza, chegando a uma redução máxima de 71 HV0,1, quando comparado às temperaturas de preaquecimento entre 150 e 400 ºC. No entanto há um severo efeito deletério na tenacidade, podendo chegar a uma queda de 71% da energia absorvida. O tratamento térmico pós soldagem (TTPS) se mostrou eficiente apenas para amostra soldada com temperaturas de preaquecimento de 150 ºC, para as demais temperaturas não houve benefício, tanto em redução de dureza, quanto na restauração da tenacidade. No entanto, para temperatura de preaquecimento de 230 ºC também foi observado o acréscimo de dureza após o TTPS devido ao efeito de endurecimento secundário por precipitação de carbonetos metálicos (MC). A técnica MPC se mostrou muito eficiente em redução da dureza e restauração da tenacidade, e este fenômeno está associado à capacidade de solubilizar os carbonetos que precipitam durante a soldagem, fenômeno que não ocorre com a aplicação do TTPS. / Currently, it is necessary to develop materials with high resistance to crack propagation, especially under conditions of cyclic loading condition such as fatigue resistant, in which its applicability is due to its mechanical properties. In the present work the effect of preheating in the heat-affected zone of the AISI / SAE 4130 steel with modified chemical composition (High Mo) was compared, regarding its mechanical and microstructural properties of each welding condition, As weld, post weld heat treated and applying the Methodology of combined preheating (MCP) with optimization of thermal cycles by combining the preheating between the 1st pass of 1st layer and the 3rd pass of 2nd layer. In order to evaluate the mechanical properties, microhardness tests, hardness mapping and charpy V notch tests were performed. For microstructural analysis, optical and scanning electron microscopy (SEM) were used to analyze the coarse grained regions and the intersections between the Heat Affected Zones (HAZ) regions, when applied to the MPC. As a result, it is observed that preheating is an effective form of reduction of hardness, reaching a maximum reduction of 71 HV0,1, when compared to the preheating temperatures between 150 and 400ºC, however there is a severe deleterious effect in the toughness, dropping up to 71% of the absorbed energy. The post weld heat treatment (PWHT) is efficient only for welded sample with preheating temperatures of 150 ºC, for the other temperatures there was no benefit, either in reduction of hardness or restoration of toughness. However, for the preheating temperature of 230 °C it was observed the increase of hardness after the PWHT due to the effect of secondary hardening by precipitation of metal carbides (MC). The MPC technique proved to be very efficient in decreasing hardness and restoring toughness, and this phenomenon is associated with the ability to solubilize the carbides that precipitate during welding, which is not observed while PWHT is applied.

Com a descoberta do prÃ-sal, a PetrobrÃs està cada vez mais investindo nas exploraÃÃes de petrÃleo em Ãguas profundas e ultra profundas, o que exige um grande dispÃndio em pesquisa e desenvolvimento (P&D) na Ãrea de produÃÃo. VÃrias estruturas submarinas sÃo soldadas e possuem juntas dissimilares, como por exemplo, em conexÃo de flowlines e risers rÃgidos com os flanges presentes em manifolds e Ãrvores de natal. Esses equipamentos sÃo geralmente protegidos com proteÃÃo catÃdica galvÃnica, a qual promove a liberaÃÃo de Ãons de hidrogÃnio na superfÃcie dos materiais. Esse hidrogÃnio adsorvido migra para regiÃo da junta susceptÃveis, facilitando a propagaÃÃo de defeitos, especialmente a trinca por hidrogÃnio. De uma forma geral este trabalho possui o objetivo de avaliar os efeitos do procedimento de soldagem TIG com alimentaÃÃo de arame frio aplicado no amanteigamento dos aÃos AISI 8630M e ASTM A182 F22, considerando o uso do TTPS em diferentes condiÃÃes de soldagens de juntas dissimilares, bem como avaliar as caracterÃsticas metalÃrgicas e propriedades mecÃnicas da interface dissimilar do amanteigamento. Os materiais de base utilizados foram o AISI 8630M e o ASTM A182F22, soldados com a liga de nÃquel AWS ER NiCrMo-3 utilizando o processo TIG com alimentaÃÃo de arame frio. Em uma primeira etapa foram realizados os testes de Higuchi Convencional e Modificado, onde foram levantados os parÃmetros para aplicaÃÃo da tÃcnica da Dupla Camada. Na segunda etapa foram fabricadas juntas dissimilares com diferentes tÃcnicas de amanteigamento, utilizando os parÃmetros aprovados e reprovados nos testes de Higuchi, como tambÃm o uso ou nÃo do tratamento tÃrmico pÃs-soldagem TTPS. Em seguida, foram retiradas amostras para anÃlises dos fenÃmenos ocorridos na interface dissimilar, assim como, suas caracterÃsticas metalÃrgicas e mecÃnicas. Foi possÃvel, por meio dos testes de Higuchi Convencional e Modificado, determinar para o aÃo AISI 8630M e ASTM A 182 F22 relaÃÃes de parÃmetros de amanteigamento que, sem necessidade do uso do TTPS, resulte em zonas termicamente afetada (ZTA) bem refinadas e com durezas prÃximas da indicada por normas. As ZTA dos aÃos AISI 8630M e ASTM A182 F22 foram compostas basicamente por martensita revenida e bainita, respectivamente, onde foi observado um intenso refino de grÃos nas juntas amanteigadas com as relaÃÃes aprovadas nos testes de Higuchi Convencional e Modificado, enquanto que uma granulaÃÃo grosseira foi observada nas juntas com condiÃÃes reprovadas nos mesmos. Os ensaios de fratura indicaram que, de forma geral, os maiores valores do fator de intensidades de tensÃes (K) foram obtidos quando as pontas do entalhe estÃo localizadas dentro da ZTA. / With the discovery of the pre-salt, Petrobras is increasingly investing in oil explorations in deep water and ultra deep, which requires a large expenditure on research and development in the area of production. Several underwater structures are welded and have dissimilar joints, e.g. in connection of flow lines and risers with rigid flanges present in manifolds and Christmas trees. This equipment are generally protected with galvanic cathode protection, which promotes the release of hydrogen ions on the surface of materials. This adsorbed hydrogen migrates to the joint which region, facilitating the spread of defects, especially the fissure by hydrogen. In general this work has the objective to evaluate the effects of procedure GTAW welding with wire feed cold applied in buttering of AISI 8630M and ASTM A182 F22, considering the use of Post-Weld Heat Treatment (PWHT) in different conditions for welding dissimilar joints, as well as evaluate the metallurgical characteristics and mechanical properties of dissimilar interface of buttering. The materials used were the AISI 8630M and ASTM A182F22, welded with the nickel alloy AWS ERNiCrMo-3 using the GTAW process with cold wire feed. In a first stage were carried Conventional and Modified Higuchi Test, where were raised the parameters for application of the technique of double layer. In the second stage were manufactured dissimilar joints with different buttering techniques, using the parameters approved and disapproved Higuchi tests, as well as the use of PWHT. Then, samples were taken for analysis of the phenomena occurring in dissimilar interface, as well as, metallurgical and mechanical characteristics. It was possible, through the of Conventional and Modified Higuchi Test, determine for Steel AISI 8630M and ASTM A 182 F22 buttering parameters relationships that, without the use of PWHT, resulting in heat affected zone (HAZ) well refined and hardness close indicated by standards. The HAZ AISI 8630M steel and ASTM A182 F22 were composed basically by tempering martensite and bainite, respectively, where it was observed an intense grain refining in the buttery joints with relations adopted in Higuchi tests while a coarse granulation was observed in the joints with disapproved on the same conditions. Fracture tests indicated that, overall, the highest values of stress intensity factor (K) were obtained when the ends of the notch are located inside the HAZ.

Esta dissertação intenta investigar como a condição de vida da escritora Higuchi Ichiyô vai modificando o seu pensamento literário levando-a à criação do universo da obra Nigorie (Enseada de águas turvas) tentando desvendar seus ideais sociais. A partir de sua visão perspicaz sobre as condições sociais do país, Ichiyô foi a primeira escritora da época a expressar de forma tão direta a tristeza das mulheres abandonadas por uma sociedade desumana. Considerando a importância da vivência pessoal de Ichiyô, um estudo sobre sua vida faz-se necessário para compreender a trajetória percorrida pela autora até a obra em questão. Ichiyô viveu nos arredores dos bairros de prostituição e manteve contato direto com o mundo das meretrizes, e essas experiências serviram-se de subsídios para a sua criação literária. Nigorie descreve a limitada e infeliz vida das mulheres socialmente degradadas que trabalham em um bairro de prostituição clandestina e os homens que o freqüentam. Sente-se em Nigorie um desejo velado de Ichiyô em denunciar ao mundo essa triste realidade e protestar contra a pobreza e o sistema social japonês de sua época. / This dissertation intends to investigate how the condition of life of writer Higuchi Ichiyô starts to modify her literary thought leading her to the creation of the universe of her work Nigorie (Troubled Creek) attempting to reveal her social ideals. From her talented vision on the social conditions of the country, Ichiyô was the first writer of her time to express in such a direct way the sadness of the women abandoned by an inhuman society. Considering the importance of the personal experience of Ichiyô a study upon her life becomes necessary to understand the trajectory the author went through as far as her work inherently. Ichiyô used to live in the outskirts of the prostitution quarters, keeping in touch with the world of prostitutes. These experiences turned into subsidies for her literary creation. Nigorie describes the limited and unhappy life of socially degraded women who work in a quarter of clandestine prostitution as well as the men who frequent it. It is felt in Nigorie a hidden desire of Ichiyô in denouncing this sad reality to the world, and besides, her intention to protest against the poverty and the Japanese social system of her time.

Esta dissertação intenta investigar como a condição de vida da escritora Higuchi Ichiyô vai modificando o seu pensamento literário levando-a à criação do universo da obra Nigorie (Enseada de águas turvas) tentando desvendar seus ideais sociais. A partir de sua visão perspicaz sobre as condições sociais do país, Ichiyô foi a primeira escritora da época a expressar de forma tão direta a tristeza das mulheres abandonadas por uma sociedade desumana. Considerando a importância da vivência pessoal de Ichiyô, um estudo sobre sua vida faz-se necessário para compreender a trajetória percorrida pela autora até a obra em questão. Ichiyô viveu nos arredores dos bairros de prostituição e manteve contato direto com o mundo das meretrizes, e essas experiências serviram-se de subsídios para a sua criação literária. Nigorie descreve a limitada e infeliz vida das mulheres socialmente degradadas que trabalham em um bairro de prostituição clandestina e os homens que o freqüentam. Sente-se em Nigorie um desejo velado de Ichiyô em denunciar ao mundo essa triste realidade e protestar contra a pobreza e o sistema social japonês de sua época. / This dissertation intends to investigate how the condition of life of writer Higuchi Ichiyô starts to modify her literary thought leading her to the creation of the universe of her work Nigorie (Troubled Creek) attempting to reveal her social ideals. From her talented vision on the social conditions of the country, Ichiyô was the first writer of her time to express in such a direct way the sadness of the women abandoned by an inhuman society. Considering the importance of the personal experience of Ichiyô a study upon her life becomes necessary to understand the trajectory the author went through as far as her work inherently. Ichiyô used to live in the outskirts of the prostitution quarters, keeping in touch with the world of prostitutes. These experiences turned into subsidies for her literary creation. Nigorie describes the limited and unhappy life of socially degraded women who work in a quarter of clandestine prostitution as well as the men who frequent it. It is felt in Nigorie a hidden desire of Ichiyô in denouncing this sad reality to the world, and besides, her intention to protest against the poverty and the Japanese social system of her time.

Esta investigación indaga sobre cómo el diario El Comercio, considerado el diario más tradicional e influyente del Perú, construyó y proyectó a través de sus encuadres o frames la imagen de la candidata de Fuerza Popular, Keiko Fujimori durante las elecciones presidenciales del año 2016. El Comercio es estudiado como un actor político por su capacidad de influir y afectar el proceso de toma de decisiones del sistema político (Borrat 1989, 2006; Page 1996). Este estudio tiene como finalidad identificar y describir los encuadres o frames estratégicos presentes en los textos del diario para presentar los atributos personales de Keiko Fujimori en la campaña. La lideresa de Fuerza Popular fue la candidata que tuvo por mucho más tiempo la mayor intención de voto y la más reseñada por los medios de comunicación durante la campaña. Los resultados del análisis de contenido son contrastados con el contexto de los hechos más relevantes de la campaña y con la postura editorial de El Comercio, con el objetivo de detectar el comportamiento político del periódico desde sus notas informativas en la primera y segunda vuelta electoral. Se identifica que en momentos de polarización, alta tensión e incertidumbre la línea informativa del diario termina coincidiendo con su posición editorial, en este caso, resaltando los encuadres con tono desfavorable respecto al equipo político de Keiko Fujimori, a su falta de credibilidad, poca coherencia en las declaraciones y actitudes de la candidata al final de la campaña. La propuesta metodológica para el análisis del contenido periodístico es la teoría de encuadre o framing, debido a que esta permite analizar la información política a partir de encuadres estratégicos que resaltan las características personales de los candidatos en coyunturas particulares como campañas electorales. Hemos recurrido a conceptos de comunicación política, comportamiento político (political behavior) y a la teoría de encuadre o framing. / Tesis

A pharmaceutical dosage form is an entity that is administered to patients so that they receive an effective dose of an active pharmaceutical ingredient (API). The proper design and formulation of a transdermal dosage form require a thorough understanding of the physiological factors affecting percutaneous penetration and physicochemical characteristics of the API, as well as that of the pharmaceutical exipients that are used during formulation. The API and pharmaceutical excipients must be compatible with one another to produce a formulation that is stable, efficacious, attractive, easy to administer, and safe (Mahato, 2007:11). Amongst others, the physicochemical properties indicate the suitability of the type of dosage form, as well as any potential problems associated with instability, poor permeation and the target site to be reached (Wells & Aulton, 2002:337). Therefore, when developing new or improved dosage forms, it is of utmost importance to evaluate the factors influencing design and formulation to provide the best possible dosage form and formulation for the API in question. Delivery of an API through the skin has long been a promising concept due to its large surface area, ease of access, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the therapy. This is true whether a local or systemic pharmacological effect is desired (Aukunuru et al., 2007:856). However, most APIs are administered orally as this route is considered to be the simplest, most convenient and safest route of API administration. Since ibuprofen is highly metabolised in the liver and gastrointestinal tract, oral administration thereof results in decreased bioavailability. Furthermore, it also causes gastric mucosal damage, bleeding and ulceration. Another obstacle associated with oral API delivery is that some APIs require continuous delivery which is difficult to achieve (Bouwstra et al., 2003:3). Therefore, there is significant interest to develop topical dosage forms for ibuprofen to avoid side effects associated with oral delivery and to provide relatively consistent API levels at the application site for prolonged periods (Rhee et al., 2003:14). The aim of this study was to determine the influence of selected formulation factors on the transdermal delivery of ibuprofen. In order to achieve this aim, the physicochemical properties of ibuprofen had to be evaluated. The aqueous solubility, pH-solubility profile, octanol-water partition coefficient (log P-value) and octanol-buffer distribution coefficient (log D-values, pH 5 and 7.4) of ibuprofen were determined. According to Naik et al., (2000:319) the ideal aqueous solubility of APIs for transdermal delivery should be more than 1 mg.ml-1. However, results showed that ibuprofen depicted an aqueous solubility of 0.096 mg.ml-1 ± 25.483, which indicated poor water solubility and would therefore be rendered less favourable for transdermal delivery if only considering the aqueous solubility. The pH-solubility profile depicted that ibuprofen was less soluble at low pH-values and more soluble at higher pH-values. Previous research indicated that the ideal log Pvalues for transdermal API permeation of non steroid anti-inflammatory drugs (NSAIDs) are between 2 and 3 (Swart et al., 2005:72). Results obtained during this study indicated a log P-value of 4.238 for ibuprofen. This value was not included in the ideal range, which is an indication that the lipophilic/hydrophilic properties are not ideal, and this might therefore; contribute to poor ibuprofen penetration through the skin. Furthermore, the obtained log D-values at pH 5 and 7.4 were 3.105 and 0.386, respectively. Therefore, it would be expected that ibuprofen incorporated into a formulation prepared at a pH of 5 would more readily permeate the skin compared to ibuprofen incorporated into a formulation prepared at a pH of 7.4. A gel, an emulgel and a Pheroid™ emulgel were formulated at pH 5 and 7.4, in order to examine which dosage form formulated at which pH would deliver enhanced transdermal delivery. Obtained diffusion results of the different semi-solid formulations were furthermore compared to a South African marketed commercial product (Nurofen® gel) in order to establish if a comparable formulation could be obtained. An artificial membrane was used to conduct the membrane permeation studies over a period of 6 h, in order to determine whether ibuprofen was in fact released from the formulations through the membrane. Skin permeation studies were conducted using Franz diffusion cells over a period of 12 h where samples were withdrawn at specified time intervals. All the formulations exhibited an increase in the average cumulative amount of ibuprofen released from the formulations and that permeated the membrane when compared to Nurofen® gel. This increase was statistically significant (p<0.05) for the gel, emulgel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest cumulative amount of ibuprofen that permeated the membrane. Preparations formulated at a pH of 5, did not differ significantly from Nurofen® when the average cumulative amount of ibuprofen that permeated the membrane were compared. The following rank order for the average cumulative amount released from the formulations could be established: Gel (pH 7.4) >>>> Pheroid™ emulgel (pH 7.4) > Emulgel (pH 7.4) >>> Gel (pH 5)> Pheroid™ emulgel (pH 5) ≈ Emulgel (pH 5) > Nurofen® gel. On the other hand, all the formulations exhibited an increase in the average cumulative amount of ibuprofen that permeated the skin when compared to Nurofen® gel. This increase was statistically significant (p < 0.05) for the gel, emulgel and Pheroid™ emulgel at pH 5, as well as the emulgel and Pheroid™ emulgel at pH 7.4. The emulgel at pH 5 exhibited the highest cumulative amount of ibuprofen that permeated the skin. The following rank order for the average cumulative amount released from the formulations and that permeated the skin could be established: Emulgel (pH 5) >> Pheroid™ emulgel (pH 5) > Gel (pH 5) > Emulgel (pH 7.4)> Pheroid™ emulgel (pH 7.4) ≈ Emulgel (pH 7.4) >> Nurofen® gel > Gel (pH 7.4). From this rank order it was clear that a trend was followed where the pH of formulation also played a role in ibuprofen permeation. All the formulations exhibited a higher release rate and flux when compared to Nurofen® gel. This was statistically significant for the emulgel, gel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest release rate and flux. This was observed for the membrane and skin permeation studies. All the formulations (including Nurofen® gel) presented a correlation coefficient (r2) of 0.972 – 0.995 for membrane permeation studies, and 0.950 – 0.978 for skin permeation studies; indicating that the release of ibuprofen from each of the formulations could be described by the Higuchi model. Furthermore, all the formulations exhibited a prolonged lag time compared to Nurofen® gel which indicated that the ibuprofen was retained for a longer time by the base. This was statistically significant (p < 0.05) for the emulgel at pH 7.4, the gel and Pheroid™ emulgel at pH 5. The gel at pH 7.4 exhibited a lag time closest to that of Nurofen® gel and this difference could not be classified as statistically significant (p > 0.286). This was observed for the membrane and skin permeation studies. Nurofen® gel exhibited the highest ibuprofen concentration in the stratum corneum as well as in the epidermis followed by the gel at pH 7.4. However, results obtained for all the formulations indicated that topical as well as transdermal delivery of ibuprofen was achieved. The pH of a formulation plays an important role with respect to API permeation. Ibuprofen is reported to have a pKa value 4.4 (Dollery, 1999:I1); and by application of the Henderson-Hasselbach equation, at pH 5, 20.08% of ibuprofen will be present in its unionised form and at pH 7.4, 0.1% ibuprofen will exist in its unionised form. Since the unionised form of APIs is more lipid soluble than the ionised form, unionised forms of APIs permeate more readily across the lipid membranes (Surber & Smith, 2000:27). Therefore, it would be expected that ibuprofen formulated at pH 5 would be more permeable than formulations at pH 7.4. However, this did not correspond to the results (membrane studies) obtained in this study. It may be attributed to the solubility of ibuprofen in the different formulations. According to the pH-solubility profile of ibuprofen obtained in this study, it was more soluble at pH 7.4 than at pH 5. This was due to the fact that ibuprofen is a weak acidic compound, and for every 3 units away from the pKa-value, the solubility changes 10-fold (Mahato, 2007:14). However, with regard to the skin permeation studies, enhanced permeation was obtained with the formulations prepared at pH 5. This was in accordance with Corrigan et al., (2003:148) who stated that NSAIDs are less soluble and more permeable at low pH values, and more soluble and less permeable at high pH values. This was most probably due to the fact that unionised species, although possessing a lower aqueous solubility than the ionised species, resulted in enhanced skin permeation due to being more lipid-soluble. Finally, stability tests on the different semi-solid formulations for a period of three months at different temperature and humidity conditions were conducted to determine product stability. The formulations were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. Stability tests included: mass variation, pH, zeta potential, droplet size, visual appearance, assay, and viscosity. No significant change was observed for mass variation, pH, zeta potential and droplet size over the three months for any of the different formulations stored at the different storage conditions. In addition, no significant change in colour was observed for the gel and emulgel formulations at pH 5 and 7.4 over the three months at all the storage conditions. However, it was observed that the formulations containing Pheroid™ showed a drastic change in colour at all the storage conditions. This might have been due to oxidation of certain components present in the Pheroid™ system. Consequently, further investigation is necessary to find the cause of the discolouration and a method to prevent it. The gel formulated at pH 5 depicted the formation of crystals. This might have been due to the fact that the solubility of ibuprofen was exceeded, leading to it precipitating from the formulation. A possible contributing factor to the varying assay values obtained during the study might have been due to non-homogenous sample withdrawal. On the other hand, no significant change was observed for the emulgel and Pheroid™ emulgel formulated at pH 5 and 7.4. The emulgel and Pheroid™ emulgel formulated at pH 5 depicted relative instability (according to the International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use, ICH) only at 40 °C/75% RH with a change in ibuprofen content of more than 5% (6.78 and 6.46%, respectively). The gel, emulgel and Pheroid™ emulgel at pH 7.4 exhibited the least variation in ibuprofen concentration at all of the storage conditions. This might indicate that the pH at which a semi-solid formulation is produced will have a direct influence on the stability of the product. No significant changes in viscosity (%RSD < 5) was observed for the gel and emulgel formulated at pH 7.4 and stored at 25 °C/60% RH. The remaining formulations at all of the specified storage conditions exhibited a significant change in viscosity (%RSD > 5) with a decrease in viscosity being more pronounced at the higher temperature and humidity storage conditions. A possible contributing factor to the change in viscosity over three months at the specified storage conditions might have been due to the use of Pluronic® F-127 (viscosity enhancer). This viscosity enhancer possesses a melting point of approximately 56 °C (BAST Corporation. s.a). The problem with this might have been the temperature (70 °C) at which the formulations were prepared. The higher preparation temperature might have caused the Pluronic® F-127 to degrade, thereby losing its ability to function appropriately. A balance must be maintained between optimum solubility and maximum stability (Pefile & Smith, 1997:148). Despite the lower skin permeation of the gel formulated at pH 7.4, this formulation performed the best, as it was considered stable (least variation during the 3 month stability test) and the obtained tape stripping results showed that this formulation depicted the highest ibuprofen concentrations in the stratum corneum and epidermis. Thus, topical as well as transdermal delivery were obtained. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

A pharmaceutical dosage form is an entity that is administered to patients so that they receive an effective dose of an active pharmaceutical ingredient (API). The proper design and formulation of a transdermal dosage form require a thorough understanding of the physiological factors affecting percutaneous penetration and physicochemical characteristics of the API, as well as that of the pharmaceutical exipients that are used during formulation. The API and pharmaceutical excipients must be compatible with one another to produce a formulation that is stable, efficacious, attractive, easy to administer, and safe (Mahato, 2007:11). Amongst others, the physicochemical properties indicate the suitability of the type of dosage form, as well as any potential problems associated with instability, poor permeation and the target site to be reached (Wells & Aulton, 2002:337). Therefore, when developing new or improved dosage forms, it is of utmost importance to evaluate the factors influencing design and formulation to provide the best possible dosage form and formulation for the API in question. Delivery of an API through the skin has long been a promising concept due to its large surface area, ease of access, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the therapy. This is true whether a local or systemic pharmacological effect is desired (Aukunuru et al., 2007:856). However, most APIs are administered orally as this route is considered to be the simplest, most convenient and safest route of API administration. Since ibuprofen is highly metabolised in the liver and gastrointestinal tract, oral administration thereof results in decreased bioavailability. Furthermore, it also causes gastric mucosal damage, bleeding and ulceration. Another obstacle associated with oral API delivery is that some APIs require continuous delivery which is difficult to achieve (Bouwstra et al., 2003:3). Therefore, there is significant interest to develop topical dosage forms for ibuprofen to avoid side effects associated with oral delivery and to provide relatively consistent API levels at the application site for prolonged periods (Rhee et al., 2003:14). The aim of this study was to determine the influence of selected formulation factors on the transdermal delivery of ibuprofen. In order to achieve this aim, the physicochemical properties of ibuprofen had to be evaluated. The aqueous solubility, pH-solubility profile, octanol-water partition coefficient (log P-value) and octanol-buffer distribution coefficient (log D-values, pH 5 and 7.4) of ibuprofen were determined. According to Naik et al., (2000:319) the ideal aqueous solubility of APIs for transdermal delivery should be more than 1 mg.ml-1. However, results showed that ibuprofen depicted an aqueous solubility of 0.096 mg.ml-1 ± 25.483, which indicated poor water solubility and would therefore be rendered less favourable for transdermal delivery if only considering the aqueous solubility. The pH-solubility profile depicted that ibuprofen was less soluble at low pH-values and more soluble at higher pH-values. Previous research indicated that the ideal log Pvalues for transdermal API permeation of non steroid anti-inflammatory drugs (NSAIDs) are between 2 and 3 (Swart et al., 2005:72). Results obtained during this study indicated a log P-value of 4.238 for ibuprofen. This value was not included in the ideal range, which is an indication that the lipophilic/hydrophilic properties are not ideal, and this might therefore; contribute to poor ibuprofen penetration through the skin. Furthermore, the obtained log D-values at pH 5 and 7.4 were 3.105 and 0.386, respectively. Therefore, it would be expected that ibuprofen incorporated into a formulation prepared at a pH of 5 would more readily permeate the skin compared to ibuprofen incorporated into a formulation prepared at a pH of 7.4. A gel, an emulgel and a Pheroid™ emulgel were formulated at pH 5 and 7.4, in order to examine which dosage form formulated at which pH would deliver enhanced transdermal delivery. Obtained diffusion results of the different semi-solid formulations were furthermore compared to a South African marketed commercial product (Nurofen® gel) in order to establish if a comparable formulation could be obtained. An artificial membrane was used to conduct the membrane permeation studies over a period of 6 h, in order to determine whether ibuprofen was in fact released from the formulations through the membrane. Skin permeation studies were conducted using Franz diffusion cells over a period of 12 h where samples were withdrawn at specified time intervals. All the formulations exhibited an increase in the average cumulative amount of ibuprofen released from the formulations and that permeated the membrane when compared to Nurofen® gel. This increase was statistically significant (p<0.05) for the gel, emulgel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest cumulative amount of ibuprofen that permeated the membrane. Preparations formulated at a pH of 5, did not differ significantly from Nurofen® when the average cumulative amount of ibuprofen that permeated the membrane were compared. The following rank order for the average cumulative amount released from the formulations could be established: Gel (pH 7.4) >>>> Pheroid™ emulgel (pH 7.4) > Emulgel (pH 7.4) >>> Gel (pH 5)> Pheroid™ emulgel (pH 5) ≈ Emulgel (pH 5) > Nurofen® gel. On the other hand, all the formulations exhibited an increase in the average cumulative amount of ibuprofen that permeated the skin when compared to Nurofen® gel. This increase was statistically significant (p < 0.05) for the gel, emulgel and Pheroid™ emulgel at pH 5, as well as the emulgel and Pheroid™ emulgel at pH 7.4. The emulgel at pH 5 exhibited the highest cumulative amount of ibuprofen that permeated the skin. The following rank order for the average cumulative amount released from the formulations and that permeated the skin could be established: Emulgel (pH 5) >> Pheroid™ emulgel (pH 5) > Gel (pH 5) > Emulgel (pH 7.4)> Pheroid™ emulgel (pH 7.4) ≈ Emulgel (pH 7.4) >> Nurofen® gel > Gel (pH 7.4). From this rank order it was clear that a trend was followed where the pH of formulation also played a role in ibuprofen permeation. All the formulations exhibited a higher release rate and flux when compared to Nurofen® gel. This was statistically significant for the emulgel, gel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest release rate and flux. This was observed for the membrane and skin permeation studies. All the formulations (including Nurofen® gel) presented a correlation coefficient (r2) of 0.972 – 0.995 for membrane permeation studies, and 0.950 – 0.978 for skin permeation studies; indicating that the release of ibuprofen from each of the formulations could be described by the Higuchi model. Furthermore, all the formulations exhibited a prolonged lag time compared to Nurofen® gel which indicated that the ibuprofen was retained for a longer time by the base. This was statistically significant (p < 0.05) for the emulgel at pH 7.4, the gel and Pheroid™ emulgel at pH 5. The gel at pH 7.4 exhibited a lag time closest to that of Nurofen® gel and this difference could not be classified as statistically significant (p > 0.286). This was observed for the membrane and skin permeation studies. Nurofen® gel exhibited the highest ibuprofen concentration in the stratum corneum as well as in the epidermis followed by the gel at pH 7.4. However, results obtained for all the formulations indicated that topical as well as transdermal delivery of ibuprofen was achieved. The pH of a formulation plays an important role with respect to API permeation. Ibuprofen is reported to have a pKa value 4.4 (Dollery, 1999:I1); and by application of the Henderson-Hasselbach equation, at pH 5, 20.08% of ibuprofen will be present in its unionised form and at pH 7.4, 0.1% ibuprofen will exist in its unionised form. Since the unionised form of APIs is more lipid soluble than the ionised form, unionised forms of APIs permeate more readily across the lipid membranes (Surber & Smith, 2000:27). Therefore, it would be expected that ibuprofen formulated at pH 5 would be more permeable than formulations at pH 7.4. However, this did not correspond to the results (membrane studies) obtained in this study. It may be attributed to the solubility of ibuprofen in the different formulations. According to the pH-solubility profile of ibuprofen obtained in this study, it was more soluble at pH 7.4 than at pH 5. This was due to the fact that ibuprofen is a weak acidic compound, and for every 3 units away from the pKa-value, the solubility changes 10-fold (Mahato, 2007:14). However, with regard to the skin permeation studies, enhanced permeation was obtained with the formulations prepared at pH 5. This was in accordance with Corrigan et al., (2003:148) who stated that NSAIDs are less soluble and more permeable at low pH values, and more soluble and less permeable at high pH values. This was most probably due to the fact that unionised species, although possessing a lower aqueous solubility than the ionised species, resulted in enhanced skin permeation due to being more lipid-soluble. Finally, stability tests on the different semi-solid formulations for a period of three months at different temperature and humidity conditions were conducted to determine product stability. The formulations were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. Stability tests included: mass variation, pH, zeta potential, droplet size, visual appearance, assay, and viscosity. No significant change was observed for mass variation, pH, zeta potential and droplet size over the three months for any of the different formulations stored at the different storage conditions. In addition, no significant change in colour was observed for the gel and emulgel formulations at pH 5 and 7.4 over the three months at all the storage conditions. However, it was observed that the formulations containing Pheroid™ showed a drastic change in colour at all the storage conditions. This might have been due to oxidation of certain components present in the Pheroid™ system. Consequently, further investigation is necessary to find the cause of the discolouration and a method to prevent it. The gel formulated at pH 5 depicted the formation of crystals. This might have been due to the fact that the solubility of ibuprofen was exceeded, leading to it precipitating from the formulation. A possible contributing factor to the varying assay values obtained during the study might have been due to non-homogenous sample withdrawal. On the other hand, no significant change was observed for the emulgel and Pheroid™ emulgel formulated at pH 5 and 7.4. The emulgel and Pheroid™ emulgel formulated at pH 5 depicted relative instability (according to the International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use, ICH) only at 40 °C/75% RH with a change in ibuprofen content of more than 5% (6.78 and 6.46%, respectively). The gel, emulgel and Pheroid™ emulgel at pH 7.4 exhibited the least variation in ibuprofen concentration at all of the storage conditions. This might indicate that the pH at which a semi-solid formulation is produced will have a direct influence on the stability of the product. No significant changes in viscosity (%RSD < 5) was observed for the gel and emulgel formulated at pH 7.4 and stored at 25 °C/60% RH. The remaining formulations at all of the specified storage conditions exhibited a significant change in viscosity (%RSD > 5) with a decrease in viscosity being more pronounced at the higher temperature and humidity storage conditions. A possible contributing factor to the change in viscosity over three months at the specified storage conditions might have been due to the use of Pluronic® F-127 (viscosity enhancer). This viscosity enhancer possesses a melting point of approximately 56 °C (BAST Corporation. s.a). The problem with this might have been the temperature (70 °C) at which the formulations were prepared. The higher preparation temperature might have caused the Pluronic® F-127 to degrade, thereby losing its ability to function appropriately. A balance must be maintained between optimum solubility and maximum stability (Pefile & Smith, 1997:148). Despite the lower skin permeation of the gel formulated at pH 7.4, this formulation performed the best, as it was considered stable (least variation during the 3 month stability test) and the obtained tape stripping results showed that this formulation depicted the highest ibuprofen concentrations in the stratum corneum and epidermis. Thus, topical as well as transdermal delivery were obtained. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

En la presente tesis se analizará la participación política y discurso de Susana Shizuko Higuchi Miyagawa, durante la campaña electoral de segunda vuelta por la presidencia del Perú en 1990 (8 de abril a 10 de junio). Se planteará, en primer lugar, la importancia de su rol como esposa de un candidato presidencial, Alberto Fujimori, desde dos papeles: madresposa y mujer nikkei. Además, a través de éstas dos pautas de presentación en el escenario electoral, Higuchi elabora un discurso, en clave emocional, que colectiviza y estimula la identificación de un sector del electorado con la candidatura fujimorista. Asimismo, el escenario electoral conforma una plataforma de visibilidad para su autopresentación y el inicio de su itinerario político. Para abordar a este personaje, se aplicará el enfoque dramatúrgico (Goffman 2001), el modelo de economías afectivas (Ahmed 2014) y el esquema lingüístico de representación discursiva de Theo Van Leeuwen. / This thesis will analyze the political participation and discourse of Susana Shizuko Higuchi Miyagawa, during the second round electoral campaign for the presidency of Peru in 1990 (April 8 to June 10). Firstly, the importance of her role as the wife of a presidential candidate, Alberto Fujimori, will be approach from two roles: mother-wife and Nikkei woman. In addition, through these two presentation guidelines on the electoral scene, Higuchi elaborates a discourse, in an emotional key, that collectivizes and stimulates the identification of a sector of the electorate with the Fujimori candidacy. Likewise, the electoral scene forms a visibility platform for their self-presentation and the beginning of their political itinerary. To address this character, the dramaturgical approach (Goffman 2001), the model of emotion as affective economy (Ahmed 2014) and the linguistic scheme of discursive representation of Theo Van Leeuwen will be applied.

This dissertation examines the discourses surrounding women and writing in the rapidly commercialized publishing industry and media in early 20th-century Japan. While Japan has a rich history of women's writing from the 10th century onwards, it was in the 1910s that the journalistic category of "women's literature" (joryû bungaku) emerged within the dominant literary mode of Naturalism, as the field of literature itself achieved a respectable cultural status after the end of the Russo-Japanese War (1904-5). Through a close textual analysis of fictional works, literary journals, and newspapers from the turn of the century to the 1930s, I explore how various women embraced, subverted, and negotiated the gendered identity of the "woman writer" (joryû sakka) while creating their own spheres of literary production through women's literary journals. Central to this investigation are issues of media, translation, canonization, and the creation of literary histories as Japanese literature became institutionalized within the new cosmopolitan notion of world literature. The first chapter explores how the image of the woman writer formed around the key figure of Tamura Toshiko (1884-1945) within the interrelated discourses of Naturalism, the New Woman, and decadence in the 1910s. As the New Woman became a social phenomenon alongside ongoing debates about women's issues, feminist women inaugurated the journal Seitô (Bluestocking, 1911-16) as a venue for women's literature. While this category renders their writings marginal to mainstream literature, it was a progressive, political position that marked their place within the literary world. I examine Toshiko's ambivalent position within this feminist project, and the instability of the media image of the New Woman that was always on the verge of slipping into the decadent figure of femme fatale. The second chapter examines the canonization of the late 19th-century prominent writer Higuchi Ichiyô (1872-96) at the turn of the century as a model woman writer and an embodiment of Japan's past tradition, which cast a threatening shadow on the women of Seitô. Tamura Toshiko's rejection of the New Woman identity and increasing association with aesthetic decadence also came to be at odds with their feminist mission. Seitô women's rejection of both Ichiyô and Toshiko was thus a necessary act in self-proclaiming the birth of the New Woman. As the number of women writers gradually increased in the late 1910s, various types of literary expression emerged beyond gendered expectations, paving the way for the mass expansion of women's writing in the 1920s. As the notion of world literature formed alongside various national literatures during the vast expansion of the publishing industry and translation culture in the 1920s, women began to envision their own alternative genealogy alongside dominant literary histories. The third chapter explores the envisioning of women's literary history by the Seitô writer Ikuta Hanayo (1888-1970) and the British modernist Virginia Woolf (1882-1941), whose feminist imaginations came together through the canonization of the English translation of The Tale of Genji, originally an 11th-century work written by a woman. As the growth of translations created a sense of global simultaneity, I further examine how the rhetoric of gender was central to Japanese literary modernism through the reception of two major British modernists, James Joyce and Virginia Woolf, in Japan.