京都大学 / 新制・課程博士 / 博士(農学) / 甲第23249号 / 農博第2456号 / 新制||農||1084(附属図書館) / 学位論文||R3||N5339(農学部図書室) / 京都大学大学院農学研究科農学専攻 / (主査)教授 松村 康生, 教授 田尾 龍太郎, 教授 丸山 伸之 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Triple fortification of salt with vitamin A, iron, and iodine has been investigated in the past to reduce micronutrient deficiencies in the developing world. The objective is to develop integrated nutrient delivery technology by microencapsulating a self-emulsifying drug delivery system (SEDDS) made of surfactants and a bioactive compound, retinyl palmitate. The SEDDS is used to enhance absorption of the vitamin A through food systems and to achieve targeted release of the active ingredient. Encapsulating vitamin A was difficult when using the spray dryer and the enteric coating, Aquacoat®. Losses of the micronutrient after a three month storage period ranged from 50-99% at both 25°C/20% RH and 45°C/60% RH. The result of a matrix encapsulation and poor coating formation contributed to the high losses. Further investigation of coating systems with the aim of stabilizing all three samples for a six month storage period such as using other encapsulating methods is recommended.

Triple fortification of salt with vitamin A, iron, and iodine has been investigated in the past to reduce micronutrient deficiencies in the developing world. The objective is to develop integrated nutrient delivery technology by microencapsulating a self-emulsifying drug delivery system (SEDDS) made of surfactants and a bioactive compound, retinyl palmitate. The SEDDS is used to enhance absorption of the vitamin A through food systems and to achieve targeted release of the active ingredient. Encapsulating vitamin A was difficult when using the spray dryer and the enteric coating, Aquacoat®. Losses of the micronutrient after a three month storage period ranged from 50-99% at both 25°C/20% RH and 45°C/60% RH. The result of a matrix encapsulation and poor coating formation contributed to the high losses. Further investigation of coating systems with the aim of stabilizing all three samples for a six month storage period such as using other encapsulating methods is recommended.

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-03-14T17:58:37Z No. of bitstreams: 1 Feitosa, Lorena Rolim [Dissertação, 2015].pdf: 1298728 bytes, checksum: 4320200a78a4a14d77c8040a33f1d227 (MD5) / Made available in DSpace on 2017-03-14T17:58:37Z (GMT). No. of bitstreams: 1 Feitosa, Lorena Rolim [Dissertação, 2015].pdf: 1298728 bytes, checksum: 4320200a78a4a14d77c8040a33f1d227 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os sistemas autoemulsificantes são misturas da fase oleosa, tensoativos e co-tensoativos, que após diluição em meio aquoso, formam um sistema emulsionado, que por sua vez, é classificado como nanoestruturado caso formem partículas tão diminutas quanto às consideradas pertencentes a essa classe. Este sistema oferece uma alternativa viável e eficiente para veicular fármacos de baixa solubilidade, como o Ibuprofeno (IBF), melhorando sua performance de dissolução e, assim, seu desempenho biofarmacotécnico. O teste de dissolução é o método oficial de avaliação do comportamento in vitro de fármacos. Os ensaios in vitro são realizados no sentido de predizer o desempenho dos fármacos in vivo. O presente estudo objetivou desenvolver sistemas autoemulsificantes contendo altas doses de IBF incorporado em capsulas gelatinosas, bem como comparar o perfil de dissolução do sistema obtido com o do IBF em pó e com os produtos comerciais Motrin® e Advil® (cápsulas líquidas contendo 200 e 400 mg de IBF, respectivamente). Inicialmente, procedeu-se um estudo de solubilidade, para identificar as matérias primas potencialmente candidatas para comporem a formulação. A solubilidade do IBF nos diferentes meios foi determinada por metodologia analítica desenvolvida por espectrofotometria UV-Vis. Após a seleção das matérias-primas candidatas, obteve-se o diagrama pseudoternário, de modo a identificar as proporções entre fase oleosa e tensoativo/cotensoativo que gerem formulações autoemulsificantes, que em seguida foram submetidas ao teste de incorporação do IBF, com a adição do fármaco em concentrações crescentes (100, 200, 300 e 400mg). A distribuição de tamanho e o potencial zeta das partículas foram avaliados, respectivamente, pelas técnicas de espalhamentodinâmico da luz e mobilidade eletroforética. Duas formulações foram selecionadas, e preparadas com 200 e 400mg de IBF, nomeadas como 1C, contendo 50% do óleo (MOD®) e 50% dos tensoativos (Tween® 80 e Span® 80, sendo a proporção entre eles de 60,3% e 39,7%, respectivamente), de modo a atender o equilíbrio hidrófilo-lipófilo (EHL) requerido pelo óleo de 10,75, e 3C, contendo os mesmos componentes, adicionado o etanol como cossolvente a 10% na fase oleosa. Estas formulações foram avaliadas quanto ao teste de desintegração e de dissolução. A desintegração das cápsulas das formulações autoemulsificantes ocorreu em menor tempo do que os produtos comerciaisMotrin® e Advil®, o que contribui para uma potencial otimização do perfil de dissolução, no que diz respeito à velocidade de liberação a partir da forma farmacêutica. Os sistemas autoemulsificantes desenvolvidos apresentaram ainda perfil de liberação in vitrootimizado quando comparados ao fármaco puro em pó e às formulações comerciais Motrin® e Advil®, quanto aos parâmetros T50%, Q30min, e eficiência de dissolução (ED). Não foi possível descrever a cinética de liberação do fármaco a partir das formulações desenvolvidas com os modelos matemáticos estudados, pois a liberação de todo o conteúdo do fármaco ocorreu de forma imediata, sendo observada nos primeiros minutos do ensaio do perfil de dissolução. O tamanho médio de partícula das formulações desenvolvidas ficou entre 44 e 124nm, sendo classificadas como sistemas autonanoemulsificantes (SNEDDS), o que provavelmente justifica a otimização do perfil de dissolução alcançado com estas formulações. Observou-se ainda que, a inclusão do cossolvente etanol (10% da fase oleosa) à formulação proporcionou maior capacidade de solubilização do IBF.Estes resultados evidenciam o potencial do sistema autoemulsificante desenvolvido em veicular de maneira eficiente altas concentrações de IBF e otimizar o perfil de liberação do fármaco a partir desses sistemas, quando comparado ao IBF em pó e a produtos comerciais disponíveis no mercado / Self-emulsifying systems are mixtures of oil phase, surfactants and co-surfactants, that after dilution in aqueous media form an emulsified system, which is classified as nanostructured, if forms particle, so small as the ones classified in that category. This system offers an effective alternative to carry low-solubility drugs, such as Ibuprofen (IBF), improving its dissolution performance and thus thebiopharmacotechnical performance. The dissolution test is the official method of evaluation of the in vitro drug performance. In vitrotests are conducted in order to predict the drug performance in vivo. The present study aimed to develop self-emulsifying systems containing high doses of IBF incorporated into gelatin capsules and compare the dissolution profile of the obtained formulation with powder IBF and commercial products Motrin® and Advil® (liquid capsules containing 200 and 400 mg of IBF, respectively).Initially, it was performed a solubility study, to identify potential candidates vehicles to compose the formulation. IBF solubility in different media was determined by analytical methodology developed by UV-Vis spectrophotometry. After selecting the candidates vehicles, it was obtained a pseudo ternary diagram, in order to identify the proportions between oil phase and surfactants /co-surfactants, that generate self emulsifying formulations, which were then conducted to IBF incorporation test, with the addition of increasing drug concentrations (100, 200, 300 and 400mg).The size distribution and zeta potential of the particles were evaluated respectively by dynamic light scattering techniques and electrophoretic mobility. Two formulations were selected and prepared with 200 and 400 mg IBF, named as 1C, containing 50% of oil (MOD®) and 50% of surfactants (Tween® 80 and Span® 80, the ratio between them 60.3 % and 39.7%, respectively), to meet the hydrophile-lipophile balance (HLB) required by the Oil of 10.75, and 3C, containing the same components, included 10% of ethanol as co-solvent in the oil phase. These formulations were evaluated for disintegration and dissolution test. Disintegration of the capsules withself emulsifying formulations occurred in less time than commercial products Motrin® and Advil®, that contributes to a potential optimization of dissolution profile, concerning the speed release from the pharmaceutical form. The self-emulsifying systems developed additionally presented optimized release profile in vitro, when compared to the pure powder drug and commercial formulations Motrin and Advil®, for the parameters T50% Q30min and dissolution efficiency (ED). It was not possible to describe the drug release kinetics from the developed formulations with the mathematical models studied, as the release of the whole drug content immediately occurred, and was observed during the first minutes of the dissolution profile test. The average particle size of the developed formulations was between 44 and 124nm, thatis classified as self-nanoemulsifyingsystems (SNEDDS), which probably explains the optimization of the dissolution profile achieved with these formulations. It was also observed that the inclusion of co-solvent ethanol (10% of oil phase) to the formulation provided higher IBF solubilization capacity. These results demonstrate the potential of the developed self-emulsifying system for efficiently carryof high concentrations IBF and optimize the drug release profile from these systems, comparing with IBF powder and commercial products available in the market

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第21811号 / 農博第2324号 / 新制||農||1066(附属図書館) / 学位論文||H31||N5183(農学部図書室) / 京都大学大学院農学研究科農学専攻 / (主査)教授 松村 康生, 教授 白岩 立彦, 教授 丸山 伸之 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 新制・論文博士 / 博士(農学) / 乙第13413号 / 論農博第2896号 / 新制||農||1085(附属図書館) / 学位論文||R3||N5323(農学部図書室) / 京都大学大学院農学研究科農学専攻 / (主査)教授 松村 康生, 教授 白岩 立彦, 教授 丸山 伸之 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

There has been growing interest in the utilization of plant-derived proteins as functional ingredients in many food and beverage applications because they are perceived as being more sustainable, healthy, and ethical than animal-derived proteins by many consumers. Traditionally, soy proteins have been the most widely employed plant protein in the food industry. However, a number of alternative plant-based protein sources have recently become available, with pulse proteins being one of the most popular. In this study, the physicochemical properties and functional attributes of various commercially available pulse protein isolates were compared with those of soy protein isolate to evaluate their potential application in foods and beverages. The water holding capacity, oil holding capacity, gelation properties, emulsifying properties, and color of faba bean (FPI), pea (PPI), lentil (LPI), and soy (SPI) protein isolates were therefore measured. SPI had a significantly higher water holding capacity (7.6 g/g) than the pulse protein isolates (2.2-5.1 g/g). Among the plant protein isolates, PPI had a significantly lower oil holding capacity and gelling property. LPI was more effective at producing small oil droplet sizes during homogenization than the other protein isolates. Nevertheless, all of the plant proteins were capable of forming relatively small oil droplets (D32 = 1-3 mm) at a protein-to-oil ratio of 1:10. As expected, droplet size decreased with increasing protein concentration for all plant protein isolates, which increased their resistance to creaming. These results suggest that pulse proteins may have similar or better techno-functional properties than soy proteins for certain applications. In particular, lentil proteins were more effective emulsifiers, whereas faba bean proteins were more effective gelling agents. These proteins may therefore be suitable for application in plant-based milks, eggs, cheese, or meats where emulsifying or gelling properties are required.

In this study, pharmaceutical-grade and food-grade linker-based lecithin self-emulsifying delivery systems (SEDS) were developed with a combination of lipophilic and hydrophilic linkers. These additives at suggested concentrations are safe for pharmaceutical and food applications. The ratio of surfactant lecithin and linkers in these systems was optimized to develop surfactant in oil preconcentrates. The preconcentrates containing different surfactant concentrations and oil were diluted with fed state simulated intestinal fluid to produce pseudo-ternary phase diagrams and to identify the formulations that produced self-emulsifying or self-microemulsifying delivery systems. Optimal SEDS preconcentrates were evaluated using a dialyzer model to simulate intestinal uptake. An uptake of 39.6 mg/cm2 for the pharmaceutical-grade SEDS was obtained within 72 minutes, which promises substantial improvement in the bioavailability of hydrophobic actives. The optimal uptake of 12.2 mg/cm2 for food-grade SEDS suggests enhancement in the bioavailability of omega-3 fatty acids.

In this study, pharmaceutical-grade and food-grade linker-based lecithin self-emulsifying delivery systems (SEDS) were developed with a combination of lipophilic and hydrophilic linkers. These additives at suggested concentrations are safe for pharmaceutical and food applications. The ratio of surfactant lecithin and linkers in these systems was optimized to develop surfactant in oil preconcentrates. The preconcentrates containing different surfactant concentrations and oil were diluted with fed state simulated intestinal fluid to produce pseudo-ternary phase diagrams and to identify the formulations that produced self-emulsifying or self-microemulsifying delivery systems. Optimal SEDS preconcentrates were evaluated using a dialyzer model to simulate intestinal uptake. An uptake of 39.6 mg/cm2 for the pharmaceutical-grade SEDS was obtained within 72 minutes, which promises substantial improvement in the bioavailability of hydrophobic actives. The optimal uptake of 12.2 mg/cm2 for food-grade SEDS suggests enhancement in the bioavailability of omega-3 fatty acids.

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