Orientador: Nelson Horacio Pezoa Garcia / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-03T20:56:29Z (GMT). No. of bitstreams: 1 Carvalho_AnaVania_D.pdf: 743758 bytes, checksum: edee8dc8e8a7a4689bdb7d3a449715ee (MD5) Previous issue date: 2004 / Resumo: O cupuaçu (Theobroma grandiflorum Schum) é uma fruta típica da região Norte do Brasil, com grande potencial econômico. Atualmente é a polpa que sustenta a produção, industrialização e comercialização desta fruta. A semente, um subproduto da industrialização da polpa, começa a despertar interesse como um produto de alto valor nutricional e com grande potencial de mercado para produtos industrializados. O presente estudo teve como objetivo a produção e caracterização de farinha, concentrado e isolado protéico da semente do cupuaçu, quanto a sua composição protéica e de aminoácidos e características químicas e funcionais. A farinha, obtida das sementes trituradas e desengorduradas, serviu como matéria-prima para a extração da fração protéica em meio aquoso, obtendo-se o concentrado protéico (precipitação em pH 3,5) e o isolado protéico (solubilização em pH 9 e precipitação em pH 3,5). A farinha desengordurada, o concentrado e o isolado protéico de semente de cupuaçu foram submetidos à análise de composição centesimal, cor, aminoácidos, perfil eletroforético de suas proteínas e propriedades funcionais. O concentrado apresentou um teor protéico de 31,18% e o isolado de 64,33%. Quanto ao perfil eletroforético de suas proteínas, observou-se a presença de três principais bandas protéicas, com pesos moleculares variando de 20,03 a 39,79kDa além de três bandas fracas adicionais. As bandas mais fracas parecem ter sido seletivamente perdidas durante a extração alcalina para produção do isolado protéico, estando presentes apenas na farinha desengordurada e no concentrado protéico. Observou-se que a farinha desengordurada, o concentrado e o isolado protéico de semente de cupuaçu, apresentaram boa composição aminoacídica, com teores superiores aos recomendados para a grande maioria dos aminoácidos. Tanto a farinha como o concentrado apresentaram muito boa capacidade de retenção de água e de óleo. Observou-se também, boa capacidade emulsificante em pH 7,0, para a farinha, o concentrado e o isolado protéico, 987,50, 977,50 e 1380,00mL óleo/g produto, respectivamente. Assim, estes produtos apresentam potencial de utilização, não somente para enriquecer outros alimentos, mas também para melhorar certas propriedades funcionais / Abstract: Cupuacu (Theobroma grandiflorum Schum) is a native fruit from northern Brazil, with great economic potential. Its productive chain is currently sustained by the pulp market. The seed, treated as a by-product of the pulp industrialization, has recently come to public attention as a highly nutritive product with great market potential for industrialized products. The objective of the present study was the production and characterization of flour, protein concentrate and protein isolate obtained from the cupuacu seed, in terms of their chemical and functional properties and their protein and amino acid composition. The flour, obtained from ground and defatted seeds, was used to extract the protein fraction in an aqueous medium, obtaining the protein concentrate (precipited at pH 3.5) and the protein isolate (solubilized at pH 9.0 and precipited at pH 3.5). The defatted flour, the protein concentrate and the protein isolate were analyzed in terms of their chemical composition, color, amino acid contents, electrophoretic protein profile and functional properties. The concentrate presented a protein content of 31.18% and the isolate, 64.29%. The electrophoretic profile of their proteins indicated the presence of three main protein bands, with molecular weights ranging from 20.03 to 39.79 kDa, besides three additional weak bands. The weaker bands seem to have been selectively lost during alkaline extraction for production of the protein isolate, as they were detected only in the defatted flour and in the protein concentrate. The defatted flour, the protein concentrate and the protein isolate obtained from cupuacu presented a good amino acid composition, as the contents of most amino acids were higher than the daily recommended amounts. The flour and the concentrate presented both excellent water and oil retention capacity. Good emulsifying ability at pH 7.0 was also observed for all three products: 987.50 mL oil/g for the flour, 977.50 mL oil/g for the protein concentrate and 1380.00 mL oil/g for the protein isolate. So, these products presented good utilization potential, not only to enrich other foods, but also to enhance some functional properties / Doutorado / Doutor em Tecnologia de Alimentos

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第15374号 / 工博第3253号 / 新制||工||1490(附属図書館) / 27852 / 京都大学大学院工学研究科原子核工学専攻 / (主査)教授 森山 裕丈, 教授 山名 元, 准教授 佐々木 隆之 / 学位規則第4条第1項該当

La cristallisation est un procédé majeur de l’industrie pharmaceutique. Dans la mise au point d’un nouveau procédé de cristallisation, l’information essentielle est la solubilité de la molécule produite dans le solvant de cristallisation. Cette donnée n’est généralement pas connue lors de la phase de développement d’un nouveau principe actif. Elle doit donc être déterminée. L’objectif de cette thèse est d’étudier, et d’approfondir, l’utilisation de modèles thermodynamiques pour prédire la solubilité de molécules organiques complexes. Pour cela, six molécules sont prises pour référence : l’ibuprofène, le paracétamol, les acides salicylique, benzoïque et 4-aminobenzoïque et l’anthracène. Les modèles étudiés sont UNIFAC et ses modifications, COSMO-SAC, NRTL-SAC et PC-SAFT. Dans un premier temps, les potentialités de chaque modèle pour prédire la solubilité dans des solvants purs et des mélanges de solvants sont analysées. Dans un second temps, le modèle COSMO-SAC est approfondi et amélioré pour la prédiction des équilibres liquide-solide mettant en jeu des molécules complexes. Enfin, une nouvelle voie de mesure expérimentale de la solubilité dans de très faibles volumes est ouverte par l’intermédiaire de l’outil microfluidique. / Crystallization is a key process of the pharmaceutical industry. When developing a new crystallization process, the most important thing to discover is the final product solubility in a given solvent. However, it is generally unknown at this early step of drug development. The solubility has to be determined. The objective of this work is to study, and deepen, the use of thermodynamic models for solubility predictions of molecules of pharmaceutical interest. To do so, six complex organic molecules have been chosen : ibuprofen, paracetamol, salicylic acid, benzoic acid, 4-aminobenzoic acid and anthracene. The studied models are UNIFAC and its modifications, COSMO-SAC, NRTL-SAC and PC-SAFT. Initially, these models are analysed and used for predicting solubility in pure and mixed solvents. Subsequent work concerns the COSMO-SAC model in more details. It is more particularly improved for solubility predictions. Finally, a road is opened for solubility measurements in low volumes with the use of microfluidics.

Magister Pharmaceuticae - MPharm / Background: Zidovudine (AZT) is a very useful drug for the management of Human Immunodeficiency Virus (HIV) infection. Its optimal use is limited by its bitter taste, sparing solubility (20.1 mg/ml) and acid lability. Cyclodextrins (CD) are a class of compounds which can be used to form inclusion complexes with drugs such as AZT to improve it is taste, solubility and palatability. Purpose: This study complexed hydroxypropyl-beta-cyclodextrin (HPβCD) with AZT. The formulated inclusion complex was evaluated for suitability as a dosage form and as a tool for improving AZT’s palatability, solubility and acid liability. Method: AZT was complexed with HPβCD using the lyophilisation method. The binding constant for the formulation was determined by the phase solubility method, and complex formation between AZT and HPβCD evaluated using proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and hot stage microscopy (HSM). Tablets of the inclusion complex were formulated by direct compression, using the least possible amount of excipients, and the dosage form evaluated for hardness, friability, durability, disintegration time and dissolution. Results: The binding constant of the formulation was 3.919, and the degree of incorporation was 4.0 mg AZT/g of CD per complex. 1H NMR showed significant chemical shifts between the inclusion complex and AZT. DSC and TGA analyses showed significant differences in the curves for the pure AZT and HPβCD. Values for tablet hardness, friability, durability and disintegration time were 236 ± 20 N, 0.7 %, 1.02 % and 10.25 minutes, respectively. The solubility of the formulation was 148.08 mg/ml, and its dissolution profile was different from that of the branded formulation. Conclusions: AZT-HPβCD inclusion complex, with a 7.4-fold increase in AZT solubility, was successfully prepared using the lyophilisation method. The binding constant and friability of the formulation were within acceptable limits. Although the hardness value is high, the tablet still disintegrated within acceptable specified times. This study has significant implications for anti-retroviral complex formulations.

Erebus is a well-studied open-vent volcano located on Ross Island, Antarctica (77◦ 32’ S, 167◦ 10’ E). The volcano is the focus of ongoing research aimed at combining petrologic data and experiments with surface gas observations in order to interpret degassing histories and the role of volatiles in magma differentiation, redox evolution, and eruptive style. This research focus has been driven in part by an abundance of studies on various aspects of the Erebus system, such as physical volcanology, gas chemistry, petrology, melt inclusion research, seismic, and more. Despite this large data set, however, interpretations of Erebus rocks, particularly mafic and intermediate lavas, which are thought to originate from deep within the magmatic plumbing system, have been hindered due to a lack of experimental data. Experimental petrology is a common tool used to understand volcanic plumb- ing systems and to tie observations made at the Earth’s surface to the deep pro- cesses responsible for driving volcanic activity. Experimental petrologists essen- tially recreate natural magma chambers in miniature by subjecting lavas to con- ditions of pressure, temperature, and volatile chemistry (P-T-X) relevant to a natural underground volcanic system. Because many important parameters can be constrained in the laboratory, the comparison of experimental products with naturally erupted ones allows for an understanding of the formation conditions of the rocks and gases we see at the surface. In this thesis, I have employed experimental and analytical petrological tech- niques to investigate the magmatic plumbing system of Erebus volcano. Broadly, the research is focused on volatiles (namely H2O, CO2, and S species) in the Ere- bus system: their abundances, solubilities, interactions, evolution, and ultimate contributions to degassing. Specifically, three key themes have been investigated, each employing their own experimental and analytical techniques. Firstly, the mixed volatile H2O-CO2 solubility in Erebus phonotephrite has been investigated under P-T-X conditions representative of the deep plumbing system of Erebus. Understanding the deep system is crucial because the constant supply of deeply derived CO2-rich gases combined with a sustained energy and mass input into the lava lake suggests a direct link between the phonolite lava lake and the volcano’s ultimate mantle source via a deep mafic plumbing system. Secondly, I have mapped the phase equilibria and evolution of primitive, inter- mediate, and evolved Erebus lavas. The chemistries of these experimental products span the full range of lavas on Ross Island and help to constrain magmatic evolu- tion from basanite to phonolite as well as to elucidate the geometry of the deep Ross Island plumbing system. Finally, lower-pressure experiments representing the shallow plumbing system at Erebus have been performed in order to understand the transport properties of sulfur in alkaline magma. Experiments were performed on natural Erebus basanite and phonolite, which represent the most primitive and evolved lavas from Erebus. A distinct cocktail of C-O-H-S fluid was equilibrated with each experiment, and a wide range of experimental oxygen fugacities was explored. Overall, experiments from this work are the first to place constraints on the en- tire magma plumbing system of Erebus volcano. In addition, experimental results foster a new understanding of non-ideal gas behavior at high pressure, the affinity of CO2 to deeply sourced rift magmas, and the effect of alkalis on fluid transport capabilities in melts.

Several studies were done to illustrate the versatillity of the Abraham model in mathematically describing the various solute-solvent interactions found in a wide range of different chemical and biological systems. The first study focused on using the solvation model to construct mathematical correlations describing the minimum inhibitory concentration of organic compounds for growth inhibition towards the three bacterial strains Porphyromonas gingivalis, Selenomonas artemidis, and Streptococcus sobrinus. The next several studies expand the practicallity of the Abraham model by predicting free energies of partition in chemical systems. The free energy studies expand the use of the Abraham model to other temperatures and properties by developing correlations for the enthalpies of solvation of gaseous solutes of various compounds dissolved in water, 1-octanol, hexane, heptane, hexadecane, cyclohexane, benzene, toluene, carbon tetrachloride, chloroform, methanol, ethanol, 1-butanol, propylene carbonate, dimethyl sulfoxide, 1,2-dichloroethane, N,N-dimethylformamide, tert-butanol, dibutyl ether, ethyl acetate, acetonitrile, and acetone. Also, a generic equation for linear alkanes is created for use when individual datasets are small. The prediction of enthalpies of solvation is furthered by modifying the Abraham model so that experimental data measured at different temperatures can be included into a single correlation expression. The temperature dependence is directly included in the model by separating each coefficient into an enthalpic and entropic component. Specifically, the final study describes the effects of temperature on the sorption coefficients of organic gases onto humic acid. The derived predicted values for each research study show a good correlation with experimental values.

The experiment successfully established the mathematical correlations between the logarithm of retention time of illegal drugs with GC system and the solute descriptor L from the Abraham model. the experiment used the method of Gas Chromatography to analyze the samples of illegal drugs and obtain the retention time of each one. Using the Abraham model to calculate and analyze the sorption coefficient of illegal drugs is an effective way to estimate the drugs. Comparison of the experimental data and calculated data shows that the Abraham linear free energy relationship (LFER) model predicts retention behavior reasonably well for most compounds. It can calculate the solute descriptors of illegal drugs from the retention time of GC system. However, the illegal drugs chosen for this experiment were not all ideal for GC analysis. HPLC is the optimal instrument and will be used for future work. HPLC analysis of the illegal drug compounds will allow for the determination of all the solute descriptors allowing one to predict the illegal drugs behavior in various Abraham biological and medical equations. the results can be applied to predict the properties in biological and medical research which the data is difficult to measure. the Abraham model will predict more accurate results by increasing the samples with effective functional groups.

Orientador: Osvaldir Pereira Taranto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-24T08:42:32Z (GMT). No. of bitstreams: 1 Souza_LucianeFranquelinGomesde_D.pdf: 6876440 bytes, checksum: af8ca21982a85f9a31f3f9b1ff3eafdc (MD5) Previous issue date: 2013 / Resumo: Microgrânulos (pellets) são formas farmacêuticas que apresentam vantagens biofarmacêuticas e, além disso, são apropriadas para aplicação de revestimento. O nifedipino é uma droga praticamente insolúvel em água, com solubilidade menor que 10 ?g/mL, de baixa e irregular biodisponibilidade depois da administração oral. Muitas pesquisas vêm sendo realizadas a fim de melhorar a solubilidade de drogas pouco hidrossolúveis fazendo o uso de desintegrantes. No Brasil, atualmente, apenas um laboratório produz comprimidos contendo nifedipino com perfil de liberação prolongada. Neste trabalho, pellets de nifedipino com matriz de liberação prolongada foram produzidos por extrusão-esferonização, e em seguida, receberam um recobrimento em leito Wurster com suspensões poliméricas de liberação imediata disponíveis no mercado, Opadry® e Opadry®II. O estudo dos processos de recobrimento foi realizado por meio de um planejamento experimental completo de dois fatores em dois níveis (22) e repetição no ponto central, para cada polímero. As variáveis estudadas foram a temperatura do ar de entrada e a vazão da suspensão de revestimento. A fração de aglomerados e a eficiência do processo foram as variáveis respostas analisadas. A temperatura do ar foi a variável que mais influenciou a eficiência do processo para ambos os polímeros e a vazão de suspensão foi o fator que mais influenciou na aglomeração durante o processo de recobrimento. Os valores de eficiência no estudo do processo se mostraram mais elevados quando o processo de recobrimento foi realizado com a suspensão polimérica Opadry®II, chegando a atingir 98%. Os pellets revestidos foram submetidos a testes de teor, dissolução in vitro e estabilidade. Os microgrânulos recobertos não tiveram o perfil de liberação prolongada alterado com os revestimentos adquiridos para ambos os polímeros. Os teores de ativo obtidos experimentalmente nos pellets mostraram-se ligeiramente inferiores aos incorporados na mistura de pós e muito próximos aos calculados pelo balanço material. Nos testes de estabilidade (40 ºC e 75% Hr) os pellets com e sem recobrimento mostraram-se estáveis quanto ao teor de ativo, perfil de dissolução e aspectos visuais. Entretanto, quando submetidos à exposição direta da luz do dia e fluorescente, os pellets recobertos perderam apenas 5% do teor, enquanto que os sem recobrimento perderam mais de 40% / Abstract: Pellets are dosage forms that have many biopharmaceutical advantages and, moreover, they are suitable for coating application. The nifedipine is a drug practically insoluble in water, with solubility of less than 10 µg/mL, low and irregular bioavailability after oral administration. Many studies have been performed in order to improve the solubility of slightly soluble drugs by the use of disintegrating. In Brazil, currently only one laboratory produces nifedipine extended release tablets. In this study, nifedipine extended release pellets were produced by extrusion-spheronization, and then received a coating layer with commercially available aqueous polymers, Opadry® and Opadry®II, in a fluid bed coater with a Wurster insert. The study of the coating processes were performed by means of a complete experimental design of two factors at two levels (22) and repetition at the central point for each polymer. The variables studied were the inlet air temperature and the coating suspension flow rate. The agglomerate fraction and process efficiency were the response variables analyzed. The air temperature was the variable that most influenced the efficiency of the process for both polymers and suspension flow rate was the most important factor involved in the agglomeration during the coating process. The process efficiency proved to be higher when the coating process was carried out with polymeric suspension Opadry ® II, reaching up to 98%. The coated pellets were tested for content, in vitro dissolution and stability. The coating layer acquired by the pellets has not changed their release profile. The nifedipine contents obtained experimentally were slightly lower than those incorporated in the mixture of powders and similar to those calculated by material balance. Not even the drug content and the release profiles were significantly affected by storage at 40 ºC and 75% relative humidity. However, when submitted to exposure to direct daylight and fluorescent light, the coated pellets lost only 5% of the drug content, while the uncoated lost more than 40% / Doutorado / Engenharia de Processos / Doutora em Engenharia Quimica

The diploma thesis deals with lignitic humic acids. Bibliographic search can be divided into three parts. The aim of the first part is characterization of humic substances, presence, composition, structure and exploitation especially of humic acids. The second part describes a division of heterogeneous mixture of humic acids into closed fractions with more specific properties. The final part is a study of solubility of humic acids. The experimental part of the diploma thesis is structured similarly. In this work, a gradual fractionation with pH is used. Obtained fractions were characterized by UV/VIS and FT-IR spectroscopy. We assessed the portion of ash and carboxyl groups have been identified. Subsequently, all fractions extracted by gradual fractionation as well as some soluble fractions obtained by direct fractionation have been analyzed in view of solubility and their behaviour in water environment. Both used methods were compared.

Tato práce se zabývá chováním huminových kyselin ve vodných roztocích a to především jejich disociací a rozpustností. Disociace huminových kyselin byla studovaná jejich částečným rozpuštěním ve vodě a v roztocích solí o různých iontových silách. Analyzované huminové kyseliny pocházely jak z lignitických tak i půdních zdrojů a jedna z nich byla upravena plazmatem. Metodami použitými při experimentech byla potenciometrie, konduktomerie a UV/VIS spektroskopie. Podle Henderson-Hasselbalchovy závislosti byly vypočítány zdánlivé disociační konstanty. Dále byly určeny zdánlivé aktivitní koeficienty kyselých funkčních skupin. Poté byla studovaná rozpustnost huminových kyselin ve vodných roztocích solí. Byly sestrojeny závislosti pH hodnot, vodivostí a absorbancí jak na obsahu huminových kyselin ve vzorku tak na iontové síle roztoku. Studována byla také kinetika disociace huminových kyselin. Získaná data byla srovnána s navrženou hypotézou předpokládající několikakrokový mechanismus disociace huminových kyselin. Chovaní všech vzorků huminových kyselin odpovídalo navrženému mechanismu. Bylo potvrzeno, že stupeň disociace huminových kyselin ve vodných roztocích klesá s rostoucím obsahem huminové kyseliny stejně tak jako ve vodných roztocích solí s rostoucí iontovou silou.