Diese Arbeit behandelt neue Konzepte zur Realisierung hocheffizienter Weißlicht emittierender organischer Leuchtdioden (OLEDs), wobei blaue fluoreszierende Emitter mit grünen und roten phosphoreszierenden Emittern kombiniert werden. Bisherige Ansätze zur Erreichung höchster Quantenausbeuten basieren auf der ausschließlichen Verwendung phosphoreszierender Emitter, da diese prinzipiell 100% der elektrisch erzeugten Exzitonen in Licht umwandeln können. Allerdings sind speziell OLEDs mit phosphoreszierenden tiefblauen Emittern heutzutage nach wie vor nicht langzeitstabil. Andererseits gibt es zwar sehr stabile fluoreszierende Emitter auch im tiefblauen Spektralbereich, jedoch kann eine rein fluoreszierende OLED aus spinstatistischen Gründen maximal nur ein Viertel der erzeugten Exzitonen in Licht umwandeln. Für eine ernsthafte Verwendung von OLEDs als Lichtquellen sind sowohl die Umwandlungseffizienz elektrischer Leistung in Lichtleistung im sichtbaren Spektralbereich, als auch ihre Langzeitstabilität entscheidend. Ein Kompromiss lässt sich daher mit der Kombination von blauen fluoreszierenden Emittern mit grünen und roten phosphoreszierenden Emittern erzielen. Die beiden in dieser Arbeit entwickelten Konzepte unterscheiden sich in der energetischen Lage des Triplettniveaus des jeweils verwendeten fluoreszierenden blauen Emitters relativ zu den verwendeten phosphoreszierenden Emittern. Das erste Konzept verwendet einen fluoreszierenden blauen Emitter mit niedriger Triplettenergie, weshalb er bei direktem Kontakt mit den phosphoreszierenden Emittern deren Phosphoreszenz löscht. Eine Exzitonen blockierende Zwischenschicht unterdrückt diesen Verlustmechanismus. Dies wird sowohl in Photolumineszenzexperimenten als auch in OLEDs nachgewiesen. Weiterhin muss die Zwischenschicht gleichzeitig die Exzitonengeneration auf beiden Seiten gewährleisten, sie muss also bipolare Transporteigenschaften haben. Mischschichten aus einem Elektronen transportierenden und einem Löcher transportierenden Material werden mit der Methode der raumladungsbegrenzten Ströme in unipolaren Strukturen untersucht, um ihren Einfluss auf die Ladungsträger- und Exzitonenbalance in OLEDs zu erklären. Das zweite Konzept verwendet einen fluoreszierenden blauen Emitter mit hoher Triplettenergie. Dadurch ergeben sich einige Vorteile. Phosphoreszenz wird nicht mehr gelöscht, weshalb keine Zwischenschicht mehr notwendig ist. Zusätzlich können außerdem die auf dem blauen fluoreszierenden Emitter erzeugten Triplettexzitonen für die Lichtemission verwendet werden, indem man sie auf die phosphoreszierenden Emitter überträgt. Damit ist es grundsätzlich möglich, 100% der elektrisch erzeugten Exzitonen für die Lichtemission zu verwenden, obwohl ein fluoreszierender Emitter verwendet wird. Allerdings ist dabei darauf zu achten, dass die Singulettexzitonen nicht ebenfalls übertragen werden, da sonst kein Weißlicht mehr erzeugt werden kann. Es werden verschiedene OLED-Strukturen untersucht, um Singulett- und Triplettexzitonen so auf die jeweiligen Emitter zu verteilen, dass eine ausgewogene spektrale Balance der Emission erreicht wird. Ein zentraler Punkt ist dabei die Ausnutzung der unterschiedlich großen Diffusionslängen von Singulett- und Triplettexzitonen.

The continuous increase in wireless usage forces an immense pressure on wireless communication in terms of increased demand and spectrum scarcity. Service providers for communication services had no choice but to allocate new parts of the spectrum and present new communication standards that are more spectrally efficient. Communication is not only limited to mobile phones but recently attention has been given to intelligent transportation systems (ITS) where cars will be given a significant place in the communication network. Vehicular Ad-Hoc Network (VANET) is already assigned a slice of the spectrum at 5.9GHz using the IEEE802.11p standard also known as Dedicated Short-Range Communication (DSRC); however, this assignment will have limited range and functionality at first, and users are expected to depend on existing wireless mobile channels for some services such as video streaming and car entertainment. Therefore, it is essential to integrate existing wireless mobile communication standards into the skeleton of ITS at launch and most probably permanently. An investigation was carried out regarding the existing communication standards including wireless local area networks (WLAN) and it was found that frequency bands from 400MHz up to 6GHz are being used in various regions around the world. It is also noted that current state of the art transceivers are composed of several transmitter front-ends targeting certain bands and standards. However, the more standards to be supported the more components to be added and the higher the cost not to mention the limited space in mobile devices. Multimode Multiband (MMMB) transmitters are therefore proposed as a potential solution to the existing redundancy in the number of front-end paths in modern transmitters. Broadband amplifiers are an essential part of any MMMB transmitter and they are also among the most challenging especially for high power requirements. This work explains why single ended topologies with efficiencies higher than 50% have a fundamental bandwidth limit such that the highest frequency of operation must be lower than twice the lowest frequency of operation. Hence, Push-Pull amplifier topology is being proposed as it was found that it has inherent broadband capabilities exceeding those of other topologies with comparable efficiency. The major advantage of Push-Pull power amplifiers is its capability of isolating the even harmonics present in the even mode operation of a Push-Pull amplifier from the less critical odd mode harmonics and the fundamental frequency. This separation between even and odd signals comes from the inclusion of a Balun at the output of push-pull amplifiers. Such separation makes it possible to operate amplifiers beyond the existing limit of single ended power amplifiers. To prove the concept, several Baluns were designed and tested and a comparison was made between different topologies in terms of balance, bandwidth and odd and even mode performances; moreover, to illustrate the concept a Push-Pull power amplifier design was implemented using the multilayer Low Temperature Co-fired Ceramics (LTCC) technology with a bandwidth ratio of more than 100%.

Emerging wireless standards are designed to be spectrally efficient to address the high cost of licensing wireless spectra. Unfortunately, the resulting signals have a high peak-to-average ratio that reduces the base station power amplifier efficiency at the back-off power level. The wasted energy is converted to heat that degrades the device reliability and increases the base-station’s carbon footprint and cooling requirements. In addition, these new standards place stringent re- quirements on the amplifier output power, linearity, efficiency, and bandwidth. To improve the back-off efficiency, a Doherty amplifier, which uses two device in parallel for back-off efficiency enhancement, is deployed in a typical base station. Unfortunately, the conventional Doherty amplifier is narrowband and thus cannot satisfy the bandwidth requirement of the modern base station that needs to support multiple standards and backward compatibility. In this thesis, we begin by studying the class F/F−1 high efficiency mode of operation. To this end, we designed a narrowband, harmonically-tuned 3.3 GHz, 10 W GaN high efficiency amplifier. Next, we investigate how to simultaneously achieve high efficiency and broad bandwidth by harnessing the simplified real frequency technique for the broadband matching network design. A 2 to 3 GHz, 45 W GaN amplifier and a 650 to 1050 MHz, 45 W LDMOS amplifier were designed. Finally, we analyze the conventional Doherty amplifier to determine the cause of its narrow bandwidth. We find that the narrow bandwidth can be attributed to the band-limited quarter-wave transformer as well as the widely adopted traditional design technique. As an original contribution to knowledge, we propose a novel Doherty amplifier configuration with intrinsically broadband characteristics by analyzing the load modulation concept and the conventional Doherty amplifier. The proposed amplifier uses asymmetrical drain voltage biases and symmetrical devices and it does not require a complex mixed-signal setup. To demonstrate the proposed concept in practice, we designed a 700 to 1000 MHz, 90 W GaN broadband Doherty amplifier. Moreover, to show that the proposed concept is applicable to high power designs, we designed a 200 W GaN broadband Doherty amplifier in the same band. In addition, to show that the technique is independent of the device technology, we designed a 700 to 900 MHz, 60 W LDMOS broadband Doherty amplifier. Using digital pre-distortion, the three prototypes were shown to be highly linearizable when driven with wideband 20 MHz LTE and WCDMA modulated signals and achieved excellent back-off efficiency. Lastly, using the insights from the previous analyses, we propose a novel mixed-technology Doherty amplifier with an extended and reconfigurable back-off level as well as an improved power utilization factor. The reconfigurability of the proposed amplifier makes it possible to customize the back-off level to achieve the highest average efficiency for a given modulated signal without redesigning the matching networks. A 790 to 960 MHz, 180 W LDMOS/GaN Doherty amplifier demonstrated the extended bandwidth and reconfigurability of the back-off level. The proposed amplifier addresses the shortcomings of the conventional Doherty amplifier and satisfies the many requirements of a modern base station power amplifier.

Emerging wireless standards are designed to be spectrally efficient to address the high cost of licensing wireless spectra. Unfortunately, the resulting signals have a high peak-to-average ratio that reduces the base station power amplifier efficiency at the back-off power level. The wasted energy is converted to heat that degrades the device reliability and increases the base-station’s carbon footprint and cooling requirements. In addition, these new standards place stringent re- quirements on the amplifier output power, linearity, efficiency, and bandwidth. To improve the back-off efficiency, a Doherty amplifier, which uses two device in parallel for back-off efficiency enhancement, is deployed in a typical base station. Unfortunately, the conventional Doherty amplifier is narrowband and thus cannot satisfy the bandwidth requirement of the modern base station that needs to support multiple standards and backward compatibility. In this thesis, we begin by studying the class F/F−1 high efficiency mode of operation. To this end, we designed a narrowband, harmonically-tuned 3.3 GHz, 10 W GaN high efficiency amplifier. Next, we investigate how to simultaneously achieve high efficiency and broad bandwidth by harnessing the simplified real frequency technique for the broadband matching network design. A 2 to 3 GHz, 45 W GaN amplifier and a 650 to 1050 MHz, 45 W LDMOS amplifier were designed. Finally, we analyze the conventional Doherty amplifier to determine the cause of its narrow bandwidth. We find that the narrow bandwidth can be attributed to the band-limited quarter-wave transformer as well as the widely adopted traditional design technique. As an original contribution to knowledge, we propose a novel Doherty amplifier configuration with intrinsically broadband characteristics by analyzing the load modulation concept and the conventional Doherty amplifier. The proposed amplifier uses asymmetrical drain voltage biases and symmetrical devices and it does not require a complex mixed-signal setup. To demonstrate the proposed concept in practice, we designed a 700 to 1000 MHz, 90 W GaN broadband Doherty amplifier. Moreover, to show that the proposed concept is applicable to high power designs, we designed a 200 W GaN broadband Doherty amplifier in the same band. In addition, to show that the technique is independent of the device technology, we designed a 700 to 900 MHz, 60 W LDMOS broadband Doherty amplifier. Using digital pre-distortion, the three prototypes were shown to be highly linearizable when driven with wideband 20 MHz LTE and WCDMA modulated signals and achieved excellent back-off efficiency. Lastly, using the insights from the previous analyses, we propose a novel mixed-technology Doherty amplifier with an extended and reconfigurable back-off level as well as an improved power utilization factor. The reconfigurability of the proposed amplifier makes it possible to customize the back-off level to achieve the highest average efficiency for a given modulated signal without redesigning the matching networks. A 790 to 960 MHz, 180 W LDMOS/GaN Doherty amplifier demonstrated the extended bandwidth and reconfigurability of the back-off level. The proposed amplifier addresses the shortcomings of the conventional Doherty amplifier and satisfies the many requirements of a modern base station power amplifier.

In wireless communication systems, multiple standards have been implemented to meet the past and present demands of different applications. This proliferation of wireless standards, operating over multiple frequency bands, has increased the demand for radio frequency (RF) components, and consequently power amplifiers (PA) to operate over multiple frequency bands. In this research work, a systematic approach for the synthesis of a novel dual-band matching network is proposed and applied for effective design of PA capable of maintaining high power efficiency at two arbitrary widely spaced frequencies. The proposed dual-band matching network incorporates two different stages. The first one aims at transforming the targeted two complex impedances, at the two operating frequencies, to a real one. The second stage is a dual-band filter that ensures the matching of the former real impedance to the termination impedance to 50 Ohm. Furthermore, an additional transmission line is incorporated between the two previously mentioned stages to adjust the impedances at the second and third harmonics without altering the impedances seen at the fundamental frequencies. Although simple, the harmonic termination control is very effective in enhancing the efficiency of RF transistors, especially when exploiting the Class J design space. The proposed dual-band matching network synthesis methodology was applied to design a dual-band power amplifier using a packaged 45 W gallium nitride (GaN) transistor. The power amplifier prototype maintained a peak power efficiency of about 68% at the two operating frequencies, namely 800 MHz and 1.9 GHz. In addition, a Volterra based digital predistortion technique has been successfully applied to linearize the PA response around the two operating frequencies. In fact, when driven with multi-carrier wideband code division multiple access (WCDMA) and long term evolution (LTE) signals, the linearized amplifier maintained an adjacent channel power ratio (ACPR) of about 50 dBc and 46 dBc, respectively.

A acne vulgaris é uma patologia cutânea crônica que acomete a unidade pilossebácea resultando em hiperqueratinização, aumento da produção de sebo, inflamação e proliferação bacteriana nos folículos pilosos. Diversos fármacos estão disponíveis para o tratamento da acne, entretanto a combinação de tratamentos tópicos, com diferentes mecanismos de ação, apresentam uma melhor eficácia. Desse modo, o presente trabalho visa o desenvolvimento de um sistema nanocarreador contendo adapaleno e dapsona no intuito de promover melhor seletividade, aumentando a eficiência do tratamento e minimizando efeitos adversos. Neste contexto, desenvolveu-se e caracterizou-se físico-quimicamente uma formulação de nanocápsulas de núcleo lipídico contendo adapaleno e dapsona. A suspensão contendo 0,025 % de adapaleno e 0,07 % de dapsona apresentou diâmetro médio de 194,9 ± 0,42 nm, índice de polidispersão de 0,12 ± 0,02, potencial zeta -15 ± 1,2 mV, pH 5,1 ± 0,1 e eficiência de encapsulação próximos a 100 %. A avaliação da morfologia por microscopia eletrônica de transmissão demonstrou partículas esféricas, homogêneas de dimensões nanométricas. Através da análise de retroespalhamento de luz dinâmico (Turbiscan®) não se detectou fenômenos de instabilidade na formulação. Uma nanoemulsão, similarmente preparada, mas sem o uso do polímero, foi desenvolvida para comparação a fim de estabelecer o mecanismo de encapsulação dos fármacos. As suspensões foram incorporadas em veículos semissólidos, hidrogéis de Carpobol® 940, e os seguintes estudos foram realizados: comportamento reológico, pH, perfil de liberação, potencial de irritação (HET-CAM) e permeação cutânea in vitro. A determinação quantitativa dos ativos foi realizada por cromatografia líquida de alta eficiência (CLAE), e os métodos analíticos foram desenvolvidos e validados de acordo com os códigos oficiais vigentes. As formulações apresentaram perfil não-Newtoniano pseudoplástico. No estudo de liberação in vitro, não houve diferença significativa entre as formulações contendo dapsona (p>0,05). Já para o adapaleno, não foi possível estabelecer o perfil de liberação in vitro por membrana de diálise. As formulações foram avaliadas como não irritantes pela técnica de HET-CAM. Através dos estudos de permeação cutânea foi possível quantificar os fármacos na epiderme e na derme, e quantidade não-significativa foi detectada no fluído receptor (p>0,05). Comparando as formulações de nanocápsula de núcleo lipídico e nanoemulsão, as quantidades de adapaleno e dapsona em cada camada da pele foi significativamente diferente (p<0,05). Em conclusão, os resultados obtidos até o presente momento demonstram que as nanocápsulas de núcleo lipídico são um sistema promissor para aplicação cutânea de adapaleno e dapsona. Contudo, estudos clínicos fazem-se necessários a fim de avaliar a efetividade da formulação no tratamento da acne. / Acne vulgaris is a chronic skin condition that affects the pilosebaceous unit resulting in hyperkeratinization, increased sebum production, inflammation and bacterial proliferation in hair follicles. Several drugs are available for treating acne, however the combination of topical treatments with different mechanisms of action presents greater effectiveness. Therefore, this study aims to develop a nanocarrier system containing adapalene and dapsone in order to promote better selectivity, increasing efficiency of treatment and minimizing adverse side effects. In this study, a suspension of lipid-core nanocapsules containing adapalene and dapsone was prepared by interfacial deposition of preformed polymer and characterized physicochemically. The suspension containing 0.025 % of adapalene and 0.07 % of dapsone showed an average diameter of 194.9 ± 0.42 nm, a polydispersity index of 0.12 ± 0.02, zeta potential -15 mV ± 1.2, pH 5.1 ± 0.1 and encapsulation efficiency approaching 100 %. The assessment of morphology by transmission electron microscopy showed spherical particles of homogeneous nanometric dimensions. No detectable instability phenomena in the formulation was observed by dynamic light scattering analysis (Turbiscan®). A nanoemulsion, similarly prepared but omitting the polymer, was developed to establish the mechanism of drug encapsulation. The suspensions were incorporated into semisolid vehicles, hydrogels of Carpobol® 940, and the following studies were performed: rheological behavior, pH, release profile, irritation potential (HET-CAM) and skin permeation in vitro. Drug quantification was carried out by high-performance liquid chromatography (HPLC) and analytical methods were developed and validated according to current official guidelines. The formulations exhibited non-Newtonian pseudoplastic profile. In the in vitro release study, no significant difference was found between the formulations containing dapsone (p>0.05). However, for adapalene, it was not possible to establish the in vitro release profile by dialysis membrane. The formulations were evaluated as non-irritant by HET-CAM technique. Through the skin permeation studies, it was possible to quantify the drug in epidermis and dermis, and non-significant quantity was detected in the receptor fluid (p>0.05). Comparing the lipid-core nanocapsules and nanoemulsion formulations, the amount of adapalene and dapsone in each skin layer was significantly different (p<0.05). In conclusion, the results obtained show that the lipid-core nanocapsules are a promising system for cutaneous application of adapalene and dapsone. However, clinical studies are required in order to evaluate the effectiveness of the formulation in the treatment of acne.

Ce travail de thèse s'inscrit dans le cadre du projet ANR FIABILITE qui porte sur la fiabilité des logiciels de simulation thermique dynamique et plus particulièrement sur les sources potentielles de biais et d'incertitude dans le domaine de la modélisation thermique et énergétique des bâtiments basse consommation. Les sollicitations telles que les occupants, la météo ou encore les scénarios de consommation des usages font partie des entrées les plus incertaines et potentiellement les plus influentes sur les performances d'un bâtiment basse consommation. Il est nécessaire pour pouvoir garantir des performances de déterminer les dispersions de sortie associées à la variabilité des entrées temporelles et d'en déterminer les variables responsables pour mieux réduire leur variabilité ou encore concevoir le bâtiment de manière robuste. Pour répondre à cette problématique, on se base sur les indices de sensibilité de Sobol adaptés aux modèles complexes à grandes dimensions tels que les modèles de bâtiment pour la simulation thermique dynamique. La gestion des entrées fonctionnelles étant un verrou scientifique pour les méthodes d'analyse de sensibilité standard, une méthodologie originale a été développée dans le cadre de cette thèse afin de générer des échantillons compatibles avec l'estimation de la sensibilité. Bien que la méthode soit générique aux entrées fonctionnelles, elle a été validée dans ce travail de thèse pour le cas des données météorologiques et tout particulièrement à partir des fichiers météo moyens (TMY) utilisés en simulation thermique dynamique. Les deux aspects principaux de ce travail de développement résident dans la caractérisation de la variabilité des données météorologiques et dans la génération des échantillons permettant l'estimation de la sensibilité de chaque variable météorologique sur la dispersion des performances d'un bâtiment. A travers différents cas d'application dérivés du modèle thermique d'une maison basse consommation, la dispersion et les paramètres influents relatifs à la variabilité météorologique sont estimés. Les résultats révèlent un intervalle d'incertitude sur les besoins énergétiques de l'ordre de 20% à 95% de niveau de confiance, dominé par la température extérieure et le rayonnement direct. / This thesis is part of the ANR project FIABILITE dealing with the reliability of dynamic thermal simulation softwares and particularly with the potential sources of bias and uncertainties in the field of thermal and energy modeling of low consumption buildings. The solicitations such as the occupancy schedules, the weather data or the usage scenarios are among the most uncertain and potentially most influential inputs on the performance of a low energy building. To ensure the efficiency of such buildings, we need to determine the outputs dispersion associated with the uncertainty of the temporal inputs as well as to emphasize the variables responsible for the dispersion of the output in order to design the building in a robust manner. To address this problem, we have used the sensitivity indices of Sobol adapted to complex models with high dimensions, such as building models for dynamic thermal simulations. The management of the functional inputs being a lock for the scientific methods of standard sensitivity analysis, an innovative methodology was developed in the framework of this thesis in order to generate consistent samples with the estimate of the sensitivity. Although the method can incorporate generic functional inputs, it has been validated in this thesis using meteorological data and especially the typical meteorological year (TMY files) used in dynamic thermal simulations. The two main aspects of this development work lie in the characterization of the variability of meteorological data and the generation of samples to estimate the sensitivity of each weather variable dispersion on the thermal and energy performances of a building. Through various case studies derived from the thermal model of a low-energy house, the dispersion and influential parameters for meteorological variability are estimated. Results show a large range of uncertainties in the energy requirements from about 20 % at a confidence level of 95%.

A acne vulgaris é uma patologia cutânea crônica que acomete a unidade pilossebácea resultando em hiperqueratinização, aumento da produção de sebo, inflamação e proliferação bacteriana nos folículos pilosos. Diversos fármacos estão disponíveis para o tratamento da acne, entretanto a combinação de tratamentos tópicos, com diferentes mecanismos de ação, apresentam uma melhor eficácia. Desse modo, o presente trabalho visa o desenvolvimento de um sistema nanocarreador contendo adapaleno e dapsona no intuito de promover melhor seletividade, aumentando a eficiência do tratamento e minimizando efeitos adversos. Neste contexto, desenvolveu-se e caracterizou-se físico-quimicamente uma formulação de nanocápsulas de núcleo lipídico contendo adapaleno e dapsona. A suspensão contendo 0,025 % de adapaleno e 0,07 % de dapsona apresentou diâmetro médio de 194,9 ± 0,42 nm, índice de polidispersão de 0,12 ± 0,02, potencial zeta -15 ± 1,2 mV, pH 5,1 ± 0,1 e eficiência de encapsulação próximos a 100 %. A avaliação da morfologia por microscopia eletrônica de transmissão demonstrou partículas esféricas, homogêneas de dimensões nanométricas. Através da análise de retroespalhamento de luz dinâmico (Turbiscan®) não se detectou fenômenos de instabilidade na formulação. Uma nanoemulsão, similarmente preparada, mas sem o uso do polímero, foi desenvolvida para comparação a fim de estabelecer o mecanismo de encapsulação dos fármacos. As suspensões foram incorporadas em veículos semissólidos, hidrogéis de Carpobol® 940, e os seguintes estudos foram realizados: comportamento reológico, pH, perfil de liberação, potencial de irritação (HET-CAM) e permeação cutânea in vitro. A determinação quantitativa dos ativos foi realizada por cromatografia líquida de alta eficiência (CLAE), e os métodos analíticos foram desenvolvidos e validados de acordo com os códigos oficiais vigentes. As formulações apresentaram perfil não-Newtoniano pseudoplástico. No estudo de liberação in vitro, não houve diferença significativa entre as formulações contendo dapsona (p>0,05). Já para o adapaleno, não foi possível estabelecer o perfil de liberação in vitro por membrana de diálise. As formulações foram avaliadas como não irritantes pela técnica de HET-CAM. Através dos estudos de permeação cutânea foi possível quantificar os fármacos na epiderme e na derme, e quantidade não-significativa foi detectada no fluído receptor (p>0,05). Comparando as formulações de nanocápsula de núcleo lipídico e nanoemulsão, as quantidades de adapaleno e dapsona em cada camada da pele foi significativamente diferente (p<0,05). Em conclusão, os resultados obtidos até o presente momento demonstram que as nanocápsulas de núcleo lipídico são um sistema promissor para aplicação cutânea de adapaleno e dapsona. Contudo, estudos clínicos fazem-se necessários a fim de avaliar a efetividade da formulação no tratamento da acne. / Acne vulgaris is a chronic skin condition that affects the pilosebaceous unit resulting in hyperkeratinization, increased sebum production, inflammation and bacterial proliferation in hair follicles. Several drugs are available for treating acne, however the combination of topical treatments with different mechanisms of action presents greater effectiveness. Therefore, this study aims to develop a nanocarrier system containing adapalene and dapsone in order to promote better selectivity, increasing efficiency of treatment and minimizing adverse side effects. In this study, a suspension of lipid-core nanocapsules containing adapalene and dapsone was prepared by interfacial deposition of preformed polymer and characterized physicochemically. The suspension containing 0.025 % of adapalene and 0.07 % of dapsone showed an average diameter of 194.9 ± 0.42 nm, a polydispersity index of 0.12 ± 0.02, zeta potential -15 mV ± 1.2, pH 5.1 ± 0.1 and encapsulation efficiency approaching 100 %. The assessment of morphology by transmission electron microscopy showed spherical particles of homogeneous nanometric dimensions. No detectable instability phenomena in the formulation was observed by dynamic light scattering analysis (Turbiscan®). A nanoemulsion, similarly prepared but omitting the polymer, was developed to establish the mechanism of drug encapsulation. The suspensions were incorporated into semisolid vehicles, hydrogels of Carpobol® 940, and the following studies were performed: rheological behavior, pH, release profile, irritation potential (HET-CAM) and skin permeation in vitro. Drug quantification was carried out by high-performance liquid chromatography (HPLC) and analytical methods were developed and validated according to current official guidelines. The formulations exhibited non-Newtonian pseudoplastic profile. In the in vitro release study, no significant difference was found between the formulations containing dapsone (p>0.05). However, for adapalene, it was not possible to establish the in vitro release profile by dialysis membrane. The formulations were evaluated as non-irritant by HET-CAM technique. Through the skin permeation studies, it was possible to quantify the drug in epidermis and dermis, and non-significant quantity was detected in the receptor fluid (p>0.05). Comparing the lipid-core nanocapsules and nanoemulsion formulations, the amount of adapalene and dapsone in each skin layer was significantly different (p<0.05). In conclusion, the results obtained show that the lipid-core nanocapsules are a promising system for cutaneous application of adapalene and dapsone. However, clinical studies are required in order to evaluate the effectiveness of the formulation in the treatment of acne.

Orientador: Admar Costa de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-02T12:28:17Z (GMT). No. of bitstreams: 1 Caro_AndreaScaboraBoix_M.pdf: 14090161 bytes, checksum: 19cff1ff37583d9e85637f916f801345 (MD5) Previous issue date: 2002 / Resumo: A presente Tese visou estudar a determinação da vitamina E, estabelecendo uma comparação entre o método clássico modificado com um outro método de determinação, a cromatografia líquida de alta eficiência (CLAE).Para efeito de comparação foram utilizados cinco tipos de amostras diferentes: suplementos vitamínicos, óleos vegetais, DDOS, farinha de germe de trigo e fígados liofilizados de ratos. Os resultados encontrados nos métodos avaliados diferiram quanto ao tipo de isômero encontrado e a quantidade total da vitamina E encontrada. Pelo método clássico modificado os resultados foram em mg Tocoferóis totaisj100g de amostra e não houve diferenciação quanto ao isômero. Na CLAE, houve a separação dos isômeros alfa, beta + gama e delta-tocoferóis e do acetato de alfa-tocoferol, sendo cada um deles quantificado. Para todas as amostras analisadas foram encontradas diferenças significativas em termos de tocoferóis totais como por exemplo, no método clássico modificado e pela CLAErespectivamente: óleo de girassol 68 e 1.426 mg T/100g; DDOS neutralizado 12.540 e 43.475 mg Tj100g; Suplemento vitamínico Ephynal@ 264 e 298.832 mg Tj100g e para os fígados de ratos liofilizados suplementados com vitamina E foi 16,1 contra 68,79 mg T/100g. Ficou então evidenciado que a CLAEforneceu resultados mais completos em termos de isômeros da vitamina E, e que os métodos propostos não foram comparáveis, pois não forneceram resultados compatíveis / Abstract: The present study aimed to study the determination of the tocopherols (vitamin-E), establishing a comparison between the modificated classic method of metallic ion reduction, more particularly cupric ions, following by complexation with specific reagents and reading of the detection of tocopherols at 292 nm) with a more recent method of separation, the high performance liquid chromatography (HPLC). To attain this objective, five types of different samples had been used: vitaminic supplements, vegetables oils, by-product of the refining of the soy oil (DDOS), wheat germ flour and liophilized rats' livers supplemented or not with vitamin-E. The results found in the two methods were different depending on the type of the found isomer and on the quantity of vitamin E. The method of ions cupric reduction show resultsin terms of total tocopherols and do not distinguish the tocopherol isomers. In the HPLC, the separation of the isomers alpha, beta + gamma an delta tocopherols and the alpha-tocopherol acetate did occurs, being each one of then quantified. For ali analyzed samples significant differences were found in terms of total tocopherols, as for example for modificated classic method: sunflower oi! 68 and 1426 mg T/100g; DDOS neutralized 12540 and 43475 mg T/100g; Ephynal@ 264 and 298832 mg T/100g and the livers of the rats that received supplementation from the vitamin-E 16,1 against 68,79 mg T/100g. It was then concluded that high performance liquid chromatography (HPLC) allowed a more detailed and accurate analysis in terms of isomers of vitamin E and the results were not comparable with the classic method / Mestrado / Nutrição Aplicada a Tecnologia de Alimentos / Mestre em Ciência de Alimentos

Orientador: Salvador Massaguer Roig / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-03T18:26:15Z (GMT). No. of bitstreams: 1 Fukuda_SandraPereira_D.pdf: 880667 bytes, checksum: 0429fa3d9dda902b36ca8200b6b18d43 (MD5) Previous issue date: 2003 / Resumo: O método da ninidrina ácida utilizando a espectrofotometria na região visível do espectro, a 470nm, para a determinação quantitativa de ácido siálico livre ou ligado ao glicomacropeptídeo - GMP da K-caseína na pesquisa de fraude de adição de soro de queijo ao leite fluido, além de ser de fácil execução, tem se mostrado eficiente na rotina laboratorial. Neste trabalho, esse método foi comparado com a metodologia por cromatografia líquida de alta eficiência - CLAE, internacionalmente aceita para a quantificação do caseinomacropeptídeo - CMP, devido à sua precisão na detecção da presença fraudulenta de soro no leite. No entanto, na proteólise também ocorre aumento dos teores de GMP/CMP livres e sua detecção poderia ser através das metodologias citadas acima. Em diversas circunstâncias amostrais (leite cru e leite adicionado intencionalmente com soro em diferentes proporções), os métodos se correlacionaram, apresentando, para um intervalo de confiança de 95%, um valor de r igual a 0,981, quando no método de ninidrina ácida se utilizou a desproteinização do leite com ácido tricloroacético TCA na concentração final de 12%. Quando se alterou a concentração final de TCA para 10% e 8%, foram obtidos valores de r iguais a 0,992 e 0,993, respectivamente. Comparou-se também os níveis de GMP e CMP encontrados no leite UAT durante o período de processamento e estocagem, partindo-se de leite cru, do leite UA T logo após a ultrapasteurização e, mensalmente, até o final de seu prazo de validade. Observou-se inicialmente uma queda dos níveis de GMP e CMP livres em ambos os métodos, entre os leites crus e recém processados, seguida de aumento significativo dos mesmos, com o decorrer do prazo de validade. O coeficiente de correlação determinado entre os resultados obtidos pelos dois métodos foi de 0,965, mostrando a elevada correspondência, confirmado pelo coeficiente de determinação da ordem de 0,93. No Brasil, as amostras de leite remetidas para análises de cromatografia líquida de alta eficiência, para detecção de fraude por adição de soro, são congeladas logo após a colheita. No estudo do efeito do congelamento em leite cru e UAT correspondente e possível influência deste processo nos valores de CMP e ácido siálico/GMP obtidos pelas metodologias de CLAE e da ninidrina ácida, respectivamente, observou-se um aumento dos valores obtidos entre o leite cru sem congelar e o congelado por 1 dia, com tendência a diminuir quando a estocagem congelada foi estendida. Para o leite UAT a tendência foi de queda suave e contínua / Abstract: The method of the acid ninidrina using the espectrofotometria in the visible region of the specter, 470nm, for the quantitative determination of acid free or on siálico to the glicomacropeptídeo - GMP of the k-casein in the research of fraud of addition of serum of cheese to fluid milk, besides being of easy execution, if has shown efficient in the laboratorial routine. In this work, this method was compared with the methodology for chromatography liquid of high efficiency - CLAE, internationally accepted for the quantification of the caseinomacropeptídeo - CMP, due to its precision in the detention of the fraudulent presence of serum in milk. However, in proteólise also increase of free texts of GMP/CMP occurs and its detention could above be through the cited methodologies. In diverse circumstances you show (raw milk and milk added intentionally with serum in different ratios), the methods if they had correlated, presenting, for a reliable interval of 95%, a value of equal r the 0.981, when in the method of acid ninidrina if it used the desproteinização of milk with acid tricloroacético - TCA in the final concentration of 12%. When the final concentration of TCA for 10% and 8% got excited, had been gotten equal values of r 0,992 and 0,993, respectively. One also compared the levels of GMP and CMP found in milk UAT during the period of processing and stockage, breaking itself of raw milk, milk UAT soon after the ultrapasteurização and, monthly, until the end of its stated period of validity. A fall of the levels of free GMP and CMP in both was observed initially the methods, between raw milk and just processings, followed of significant increase of the same ones, with elapsing of the validity stated period. The determined coefficient of correlation enters the results gotten for the two methods was of 0,965, showing the raised correspondence, confirmed for the coefficient of determination of the order of 0,93. In Brazil, the sent milk samples for analyses of liquid chromatography of high efficiency, for detention of fraud for serum addition, are congealed after the harvest soon. In the study of the effect of the freezing in corresponding raw milk and UAT and possible influence of this process in the values of acid CMP and siálico/GMP gotten by the CLAE methodologies and of the acid ninidrina, respectively, observed an increase of the values gotten between raw milk without congealing and the frozen one per 1 day, with trend to diminish when the frozen stockage was extended. For milk UAT the trend was of soft and continuous fall / Doutorado / Doutor em Tecnologia de Alimentos