Le combustible nucléaire usé, constitué d’uranium, de plutonium et de produits de fission (palladium, technétium, molybdène etc.), est traité industriellement en France par le procédé PUREX. Ce procédé hydrométallurgique permet d’extraire l’uranium et le plutonium à l’aide d’une phase organique composée de tri-n-butylphosphate (TBP) dilué dans un mélange d’hydrocarbures aliphatiques (TPH). Au cours des différents cycles d’extraction, la phase organique est soumise à des phénomènes d’hydrolyse acide et de radiolyse conduisant à la formation de produits de dégradation. Afin d’assurer le recyclage du solvant organique et le bon fonctionnement du procédé industriel, un traitement approprié permet d’éliminer ces produits. Néanmoins, après plusieurs décennies de fonctionnement des usines, des encrassements de certains équipements ont été observés. Ces solides contiennent les éléments palladium, carbone, oxygène et azote. Industriellement, une solution curative a été mise en œuvre pour éliminer ces crasses. Il convient toutefois de comprendre les phénomènes qui ont conduit à leur formation. Ce travail de doctorat a pour objectif d’étudier le comportement physico-chimique du palladium dans les cycles d’extraction et les mécanismes conduisant à la formation de solides. Pour cela, un système biphasique, constitué d’une phase organique de TBP dilué dans le TPH et d’une phase aqueuse d’acide nitrique contenant du nitrate de palladium(II), a été irradié par une source externe de rayonnement gamma afin de simuler le vieillissement du solvant d’extraction. Des précipités non radioactifs contenant du palladium et représentatifs des encrassements industriels ont été obtenus. Des analyses multi-techniques de ces précipités ont montré que les solides sont constitués d’un mélange complexe de cyanure de palladium(II), de carboxylate de palladium(II) et de divers produits organiques (di-n-butylphosphate (HDBP), composés à fonctions amines et hydrazine). Les produits menant à la précipitation du palladium proviennent de la dégradation du TBP et de celle du TPH et sont présents en phase aqueuse et en phase organique.Certains produits de dégradation formés lors de l’irradiation semblent favoriser l’extraction du palladium. Pour comprendre le rôle des produits de dégradation sur l’extraction du palladium, le solvant d’extraction utilisé dans le procédé PUREX a été dopé en composés organiques. Les composés testés sont des composés commerciaux représentatifs de produits de dégradation identifiés un solvant dégradé. De plus, les espèces testées sont des composés susceptibles d’interagir avec le palladium(II) (cétone, acide carboxylique, alcool, aldéhyde et alcène). Parmi ces composés, seul le 5-dodécène conduit à une augmentation significative de l’extraction du palladium(II) par rapport à une phase organique non dopée et à la formation d’un précipité noir constitué de palladium métal. Les analyses réalisées sur la phase organique dopée en 5-dodécène ont mis en évidence la formation d’un complexe ternaire dans lequel le palladium serait entouré de molécules de TBP, de 5-dodécène et d’ions nitrate. Par ailleurs, une fraction du palladium(II) extrait dans la phase organique oxyde le 5-dodécène en cétone et est réduit en palladium métal (précipité noir). Des voies de formation des différents composés constituant les crasses ont été proposées. Les alcènes, les cétones et l’acide nitreux apparaissent comme des précurseurs dans la formation de cyanure de palladium(II). Un carboxylate de palladium(II) serait formé par réaction de palladium(II) avec l’acide carboxylique correspondant. Les amines primaires pourraient se former par hydrogénation des nitroalcanes catalysé par la présence de palladium métal tandis que l’hydrazine pourrait se former par radiolyse des amines primaires. / The spent nuclear fuel composed of uranium, plutonium and fission products (such as palladium, technetium, molybdenum, etc.) is industrially processed in France by the PUREX process. This hydrometallurgical process allows separating uranium and plutonium by using an organic phase composed of tri-n-butyl phosphate (TBP) diluted in a mixture of aliphatic hydrocarbons (TPH = tetra propylene hydrogen). During the various extraction cycles, the organic phase is subjected to acid hydrolysis and radiolysis phenomena leading to the formation of degradation products. To ensure the recycling of the organic solvent and a normal operation of the industrial process, an appropriate treatment eliminates these degradation products. Nevertheless, after several decades of industrial operation of the factories, precipitates have been observed in some equipments. These solids contain palladium, carbon, oxygen and nitrogen atoms. Industrially, a curative solution has been found and allows eliminating these cruds containing in particular palladium. However, it is important to understand the formation of palladium precipitates in the liquid-liquid extraction cycles. This thesis aims to study the behavior of palladium in the extraction cycles and the mechanisms leading to the formation of solids.For this purpose, a biphasic system containing an organic phase of TBP diluted in TPH and a aqueous phase of nitric acid containing palladium(II) nitrate has been irradiated by an external source (gamma-irradiation). This irradiation allows simulating the aging of the extraction solvent. Nonradioactive precipitates which are representative of the industrial crud were obtained. A multi-technical analysis of these inactive precipitates has shown that the solids are composed of a complex mixture: (i) palladium cyanide(II), (ii) palladium(II) carboxylate and (iii) various organic products (di-n-butyl phosphate (HDBP)), compounds with amine functions and hydrazine. Moreover, we demonstrate that the degradation products leading to the precipitation of palladium come from either TBP or TPH and are present in the aqueous phase and in the organic phase.Some degradation products formed during irradiation seem to favor the extraction of palladium(II). To understand the role of degradation products on palladium extraction, the extraction solvent used in the PUREX process was doped with organic compounds. The compounds tested are commercial compounds representative of degradation products identified a degraded solvent. In addition, the compounds tested are species which can react with palladium(II) (ketone, carboxylic acid, alcohol, aldehyde and alkene). Among these compounds, only 5-dodecene leads to a significant increase in the extraction of palladium(II) in comparison with an undoped organic phase and the formation of a black precipitate composed of palladium metal. The analyses carried out on the 5-dodecene-doped organic phase revealed the formation of a ternary complex in which the palladium would be surrounded by TBP molécules, 5-dodecene and nitrate ions. In addition, a fraction of the palladium(II) extracted in the organic phase oxidizes the 5-dodecene to ketone and is reduced to palladium metal (black precipitate).Formation pathways of the various compounds present in the nonradioactive solids have been proposed. Alkenes, ketones and nitrous acid appear as precursors in the formation of palladium cyanide(II). A palladium(II) carboxylate would be formed by reaction of palladium(II) with the corresponding carboxylic acid. Primary amines could be formed by hydrogenation of nitroalkanes catalyzed by the presence of palladium metal while hydrazine could be formed by radiolysis of primary amines.Key word: palladium, radiolysis, PUREX process, degradation products, precipitates

No description available.

Em julho de 2008, a ANVISA publicou um informe técnico esclarecendo um item importante da RE nº 1 (2005), que trata sobre os estudos de estabilidade de medicamentos. Este documento originou uma nova RDC de nº 58, publicada em dezembro de 2013, a qual estabelece limites para produtos de degradação em medicamentos. O objetivo do presente trabalho foi avaliar o comportamento do antineoplástico cloridrato de doxorrubicina frente a condições de decomposição (hidrólise ácida, básica, oxidação, temperatura e fotólise), a fim de se determinar suas principais vias de degradação e também elucidar as estruturas de seus principais produtos de degradação. Para isso foi desenvolvido e validado um método indicativo de estabilidade por HPLC-DAD-MS, o qual utiliza como fase estacionária uma coluna Luna C18(2) (150 mm x 3,0 mm, µm) com gradiente de fase móvel de tampão formiato de amônio 5 mmoles.L-1 pH 3 e metanol e fluxo de 0,3 mL.min-1. Ao longo do estudo foram encontrados diversos produtos de degradação, dentre eles a 7- deoxidehidrodoxorrubicinona, originada por hidrólise ácida e também o produto da degradação térmica de m/z 530, o qual foi encontrado nas análises do medicamento após expirado seu prazo de validade. Além disso, a avaliação da toxicidade in vitro de amostras contendo produtos de degradação de origem térmica indicou atividade citotóxica para células mononucleares. / ANVISA has published in July 2008, a technical sheet expaining an important item of the RE No. 1 (2005), which describes drugs stability studies. This document originated a new RDC No. 58, published in December 2013, which sets thresholds for degradation products in pharmaceuticals. The aim of this study was to evaluate the behavior for the antineoplastic doxorubicin when exposed to stress conditions (acid and base hydrolysis, oxidaton, photolysis and temperature) in order to determine the major pathaways of degradation and also to elucidate the stuctures of their main degradation products. To this was developed and validated a target stability indicatinf method by HPLC-DAD-MS, with Luna C18 (2) (150 mm x 3.0 mm. 3 µm) column as stationary phase and a mobile phase gradient composed of ammonium formate buffer 5 mmoles.L-1 and pH 3 and metanol with flow of 0.3 ml min-1. Throughout the study many degradation products was discovered, among them 7- deoxydehydrodoxorubicinone, formed by acid hydrolysis and also the main product of termal decomposition of m/z 530, wich was found in the analyzes of the medicine after the expiry of its validity were found. Furthermore, evaluation of the in vitro toxicity of samples containing degradation products of thermal decomposition was found to be citotoxic for mononuclear cells.

A contaminação do ambiente aquático e até mesmo da água de consumo por produtos farmacêuticos e de cuidados pessoais (PFCPs) é resultado das atividades antrópicas. Entre as tecnologias de tratamento de água, a filtração ecológica (modernização do termo filtro lento de areia) é atraente por ser um método natural de tratamento, de baixo custo e eficiência na remoção de patógenos e pode ser utilizada não só em grande escala, mas também domiciliar. O objetivo desta pesquisa foi avaliar a aplicabilidade dos filtros ecológicos abastecidos com água do Reservatório do Lobo, e a eficiência em remover produtos farmacêuticos e de cuidados pessoais. Além disso, foi avaliado o efeito da contaminação nas comunidades de algas e cianobactérias e de bactérias, presentes no biofilme dos filtros ecológicos. Os filtros ecológicos apresentaram boa remoção de coliformes fecais e Escherichia coli. Os PFCPs alvos deste estudo foram encontrados na água do Reservatório do Lobo em concentração da ordem de &#956g L-1. Os produtos de cuidados pessoais, metilparabeno e benzofenona-3,estiveram presentes em todas as amostras de água coletadas e foram os compostos encontrados em maior concentração no reservatório. Dois produtos de degradação dos compostos originais diclofenaco e benzofenona-3 foram identificados na água do reservatório. A porcentagem média global de remoção dos PFCPs pelos filtros ecológicos foi de 81,09% de paracetamol, 91,07% de diclofenaco, 97,33% de naproxeno, 99,57% de ibuprofeno, 70,81% de metilparabeno e 71,69% de benzofenona-3. Foi observado efeito da contaminação na comunidade de algas e cianobactérias. Aulacoseiragranulata, Chroococcus minutus, Dolichospermum planctonicum e Microcystis aeruginosa foram as espécies de algas e cianobactérias consideradas como descritoras em comum para todas as contaminações e tempos de coleta. Lepocincles sp. foi a espécie que mais contribuiu em biovolume durante o período experimental. A ocorrência, abundância e frequência destas espécies indicam uma possível tolerância das mesmas aos PFCPs. O desempenho dos filtros ecológicos de uso doméstico não foi afetado pela presença de 2 μg L-1 de PFCPs na água afluente. As espécies Bacillus anthracis e Exiquobacterium sp. foram resistentes aos compostos aplicados no filtro 2. A concentração de biomassa nos filtros aumentou significativamente com o tempo de operação e foi expressa em uma função exponencial de crescimento, mas não houve diferença significativa entre o filtro controle e o contaminado. / The contamination of the aquatic environment and even the water consumption with pharmaceutical and personal care products (PPCPs) is a result of human activities. Among the water treatment technologies, the ecological filtration (modern name for slow sand filter) is attractive because it is a natural treatment method, low cost and efficiency in removing pathogens and can be used not only in large scale, but also household. The objective of this research was to evaluate the applicability of ecological filters supplied with water from the Lobo Reservoir, and the efficiency in remove pharmaceuticals and personal care products. Furthermore, it was evaluated the effect of contamination in the communities of algae and cyanobacteria and bacteria, in the biofilm of the ecological filters. The ecological filters showed good removal of total coliforms and E. coli. The PPCPs aims of this study were found in the water from the Lobo Reservoir in order of &#956g L-1 of concentration. The personal care products, methylparaben and benzophenone-3, were present in all water samples, and the compounds were found at higher concentration in the reservoir. Two degradation products of the original compounds diclofenac and benzophenone-3 were identified in the water from reservoir. The overall average percentage of removal of PPCPs by ecological filters was 81,09% of paracetamol, 91,07% of diclofenac, 97,33% of naproxen, 99,57% of ibuprofen, 70,81% of methylparaben and 71,69% of benzophenone-3. It was observed an effect caused by contamination in the community of algae and cyanobacteria. Aulacoseira granulata, Chroococcus minutus, Dolichospermum planctonicum and Microcystis aeruginosa were the species of algae and cyanobacteria considered as descriptors in common for all contamination and collection times. Lepocincles sp. was the specie that most contributed in biovolume during the period. The occurrence, abundance and frequency of these species indicate a possible tolerance thereof to PPCPs. The performance of household ecological filters was not affected by the presence of 2 &#956g L-1 of PPCPs in affluent water. The species of bacteria Bacillus anthracis and Exiquobacterium sp. were resistant for the compound applied to the filter 2. The filter biomass concentration increased significantly with filter time and was summarised by an exponential growth function in both filters, but there was no substantial difference between the filter control and contaminated.

No contexto de qualidade, segurança e eficácia dos medicamentos, os produtos de degradação surgem com um crescente foco regulatório no Brasil e no mundo. Para análise confiável dos medicamentos, métodos indicativos de estabilidade devem ser utilizados, visando a avaliação qualitativa e quantitativa das impurezas e dos produtos de degradação neles contidos. O cloridrato de propafenona é utilizado no tratamento de arritmias supraventriculares e ventriculares, apresentando-se como bloqueadores dos canais de sódio, além de ser um betabloqueador. O cloridrato de pioglitazona é um agente anti-hiperglicemiante que atua primariamente diminuindo a resistência à insulina, no tratamento da Diabetes tipo 2. Os métodos oficiais descritos nas farmacopeias, muitas vezes, não fornecem informações a respeito de análise de impurezas farmacêuticas e de produtos de degradação. Assim sendo, deve-se verificar se os métodos são indicativos da estabilidade, antes de utilizá-los para analisar os produtos de degradação. A presente pesquisa tem como objetivo avaliar amostras simuladas dos medicamentos citados, após serem submetidos a condições de estresse; determinar os principais produtos de degradação através dos métodos descritos na Farmacopeia Americana e avaliar se tais métodos são indicativos de estabilidade, assim como realizar balanço de massa. Foi realizado um delineamento fatorial 32 dos meios de degradação avaliando-se a variação do tempo e da intensidade e a capacidade de detecção e quantificação de produtos de degradação presentes. Os fatores considerados no delineamento foram degradação ácida, alcalina, meio oxidativo com peróxido de hidrogênio, e temperatura/umidade além da fotoestabilidade. O cloridrato de propafenona apresentou degradação nos estresses ácidos, oxidativos e em temperatura/umidade. No meio alcalino e a exposição a luz (branca/UV), a magnitude da degradação foi amena. Houve um balanço de massas entre os métodos de doseamento e de impurezas, mostrando-se que o método é indicativo de estabilidade. O principal produto de degradação, no meio ácido e oxidativo, foi identificado utilizando o método de LC-MS. O cloridrato de pioglitazona apresentou degradação em meios básicos, oxidativos assim como em exposição à luz e elevada temperatura/umidade. A hidrólise ácida não apresentou impacto significativo. Os métodos de doseamento e de impurezas não apresentaram balanço de massa, mostrando-se que o método não é indicativo de estabilidade. As análises in silico, com o software Zeneth®, foi utilizada para estabelecer correlações entre o processo de degradação e os plausíveis produtos formados. Assim, conclui-se que os dados de estresses obtidos, neste trabalho, podem servir como suporte nos estudos de estabilidade, bem como contribuir na definição das condições de transporte e armazenamento do cloridrato de propafenona e cloridrato de pioglitazona. / In the context of quality, safety and efficacy of pharmaceuticals, degradation products ascend with a growing regulatory focus in Brazil and in the world. For reliable analysis of pharmaceutical products, stability indicative methods must be used, aiming at qualitative and quantitative analysis of impurities and degradation products contained therein. Propafenone HCl is used in the treatment of supraventricular and ventricular arrhythmias and has sodium channel blocking capacity, besides its betareceptor blocking activity. Pioglitazone HCl is an anti-hiperglicemiante agent that acts primarily by reducing insulin resistance in the treatment of type 2 diabetes. The official methods described in the Pharmacopoeias often do not provide information regarding the analysis of pharmaceutical impurities and degradation products. Therefore, it important to verified whether the methods are stability indicative or not, before being use in the analysis of degradation products. The objective of this research is to evaluate simulated samples of cited pharmaceuticals, after submission to stress conditions. To determine the main degradation products through the methods described in the American Pharmacopoeia and assess whether such methods are indicative of stability by mass balance approach. A factorial design (32) of the degradation mediums was carried out to evaluate impact of time of contact and variable intensity. On the outer side, the ability of the method to detect and quantify degradation products was also assessed. The degradation medium factors considered in the design were, acid, alkaline, oxidant medium using hydrogen peroxide, temperature/humidity and photostability. Propafenone hydrochloride presented degradation in acid, oxidative and temperature/humidity stress conditions. In the alkaline medium and exposure to light (white/UV), the extent of degradation was mild. There was a mass balance between the assay method and impurity method, illustrating that the method is stability indicative. The main degradation product, in the acidic and oxidative medium, was identified using the LC-MS method. Pioglitazone hydrochloride presented degradation in basic, oxidative means as well as on exposure to light and elevated temperature/humidity conditions. Acidic hydrolysis has no significant impact. The assay and impurity methods did not show mass balance, elucidating that the method is not stability indicative. In silico analysis, with the Zeneth® software, was used to establish correlations between the degradation process and the plausible degradation pathway and products. Thus, it is concluded that the data obtained in degradation studies, in this work, may serve as support in the stability studies, as well as subsidize to define transport and storage conditions for propafenone HCl and pioglitazone HCl.

Em julho de 2008, a ANVISA publicou um informe técnico esclarecendo um item importante da RE nº 1 (2005), que trata sobre os estudos de estabilidade de medicamentos. Este documento originou uma nova RDC de nº 58, publicada em dezembro de 2013, a qual estabelece limites para produtos de degradação em medicamentos. O objetivo do presente trabalho foi avaliar o comportamento do antineoplástico cloridrato de doxorrubicina frente a condições de decomposição (hidrólise ácida, básica, oxidação, temperatura e fotólise), a fim de se determinar suas principais vias de degradação e também elucidar as estruturas de seus principais produtos de degradação. Para isso foi desenvolvido e validado um método indicativo de estabilidade por HPLC-DAD-MS, o qual utiliza como fase estacionária uma coluna Luna C18(2) (150 mm x 3,0 mm, µm) com gradiente de fase móvel de tampão formiato de amônio 5 mmoles.L-1 pH 3 e metanol e fluxo de 0,3 mL.min-1. Ao longo do estudo foram encontrados diversos produtos de degradação, dentre eles a 7- deoxidehidrodoxorrubicinona, originada por hidrólise ácida e também o produto da degradação térmica de m/z 530, o qual foi encontrado nas análises do medicamento após expirado seu prazo de validade. Além disso, a avaliação da toxicidade in vitro de amostras contendo produtos de degradação de origem térmica indicou atividade citotóxica para células mononucleares. / ANVISA has published in July 2008, a technical sheet expaining an important item of the RE No. 1 (2005), which describes drugs stability studies. This document originated a new RDC No. 58, published in December 2013, which sets thresholds for degradation products in pharmaceuticals. The aim of this study was to evaluate the behavior for the antineoplastic doxorubicin when exposed to stress conditions (acid and base hydrolysis, oxidaton, photolysis and temperature) in order to determine the major pathaways of degradation and also to elucidate the stuctures of their main degradation products. To this was developed and validated a target stability indicatinf method by HPLC-DAD-MS, with Luna C18 (2) (150 mm x 3.0 mm. 3 µm) column as stationary phase and a mobile phase gradient composed of ammonium formate buffer 5 mmoles.L-1 and pH 3 and metanol with flow of 0.3 ml min-1. Throughout the study many degradation products was discovered, among them 7- deoxydehydrodoxorubicinone, formed by acid hydrolysis and also the main product of termal decomposition of m/z 530, wich was found in the analyzes of the medicine after the expiry of its validity were found. Furthermore, evaluation of the in vitro toxicity of samples containing degradation products of thermal decomposition was found to be citotoxic for mononuclear cells.

Le procédé de captage du CO2 en post-combustion par absorption chimique est aujourd'hui la technologie la plus mature en vue d'une réduction des émissions de CO2 issues de procédés industriels. Les deux principales limitations de la technologie sont la pénalité énergétique engendrée par le procédé, et la formation de produits de dégradation potentiellement toxiques pour l'Homme et l'environnement. Dans le cadre de ce projet de thèse, trois solvants innovants ont été présélectionnés pour leurs bonnes propriétés thermodynamiques de captage : les mélanges 1-méthylpipérazine / pipérazine (1MPZ /PZ), diméthylaminoéthanol / pipérazine (DMEA/PZ) et méthyldiéthanolamine/monoéthanolamine (MDEA/MEA). Ces trois solvants ont été étudiés en termes de stabilité chimique dans des conditions représentatives des conditions industrielles du captage de CO2 en post-combustion sur un dispositif expérimental construit par EDF R&D Chatou. Des méthodes analytiques complémentaires impliquant les chromatographies liquide et gazeuse ont été développées dans l'objectif de suivre les teneurs en amines constituantes du solvant au cours du temps, et d'identifier et quantifier les potentiels produits de dégradation formés aussi bien dans la phase liquide du solvant que dans les fumées traitées émises. Au vu des résultats obtenus au cours de ce projet, le solvant MDEA/MEA semble offrir le meilleur compromis en termes de stabilité chimique et de besoins énergétiques requis pour le procédé. Ce solvant présente des taux de dégradation inférieurs aux mélanges 1MPZ/PZ et DMEA/PZ, et permettrait une réduction de l'énergie au rebouilleur de l'ordre de 10 % par rapport à la MEA 30 %, solvant modèle au procédé. / Post-combustion CO2 capture using amine solvents is nowadays the most promising technology to limit the CO2 emissions from already existing power plants. The two main limitations of the process are the high energy penalty and the irreversible degradation of amines involving the formation of degradation products potentially toxic for human and the environment. Within the scope of this project, three innovative solvents were selected for their good thermodynamic properties for CO2 capture: the blends 1-methylpiperazine / piperazine (1MPZ/PZ), dimethylaminoethanol / piperazine (DMEA/PZ) and methyldiethanolamine/monoethanolamine (MDEA/MEA). The three blends were degraded in conditions representative of industrial conditions for post-combustion CO2 capture on a lab scale pilot plant constructed by EDF R&D. Complementary analytical methods involving gas and liquid chromatography were developed in order to monitor the stability of the constituent amines, and to identify and quantify potential degradation products formed. These methods permitted the characterization of both the liquid phase of the solvent and the gaseous phase corresponding to the treated flue gas. Results obtained during this project showed that the blend MDEA/MEA would offer the best compromise in terms of chemical stability and energy needed for the process. This solvent presents degradation rates lower than the blends 1MPZ/PZ and DMEA/PZ and would enable a reduction of the reboiler heat duty in the range of 10% when compared to MEA 30% the benchmark solvent of the process.

Linear and branched poly(butylene adipate) polyesters with number-average molecular weights ranging from 700 to 10 000 g/mol, and degrees of branching ranging from very low to hyperbranched were solution cast with PVC to study the effects of chemical structure, molecular weight, end-group functionality, and chain architecture on plasticizing efficiency and durability. Miscibility was evaluated by the existence of a single glass transition temperature and a shift of the carbonyl group absorption band. Desirable mechanical properties were achieved in flexible PVC films containing 40 weight-% of polyester plasticizer. Methyl-ester-terminated polyesters with a low degree of branching and an intermediate molecular weight enhanced the plasticizing efficiency, as shown by greater elongation, good miscibility, and reduced surface segregation. A solid-phase extraction method was developed to extract the low molecular weight products that migrated from pure poly(butylene adipate) and PVC/ poly(butylene adipate) films during aging in water. The effects of branching, molecular weight, end-group functionality, and polydispersity on plasticizer permanence were evaluated by quantification of low molecular weight hydrolysis products, weight loss, surface segregation, and the preservation of material properties during aging. A more migration-resistant polymeric plasticizer was obtained by combining a low degree of branching, hydrolysis-protecting end-groups, and higher molecular weight of the polyester. Films plasticized with a slightly branched polyester showed the best durability and preservation of material and mechanical properties during aging. A high degree of branching resulted in partial miscibility with PVC, poor mechanical properties, and low migration resistance. The thermal stability of polyester-plasticized films was higher than that of films containing a low molecular weight plasticizer, and the stabilizing effect increased with increasing plasticizer concentration. / QC 20100805

<p>A solid phase extraction (SPE) method was developed for simultaneous extraction of dicarboxylic acids and diols formed during hydrolysis of poly(butylene succinate), PBS, and poly(butylene adipate), PBA. The developed SPE method and subsequent GC-MS analysis were used to extract, identify and quantify low molecular weight products migrating from linear and branched poly(butylene adipate) (PBA) and poly(butylene succinate) (PBS) during aging in aqueous media. The combination of SPE and GC-MS proved to be a sensitive tool, able to detect small differences in the degradation rate during early stages of hydrolysis before any significant differences were observed by weight loss and molecular weight measurements. The detected low molecular weight products included monomers i.e. adipic acid and 1,4-butanediol for the PBA polymers and succinic acid and 1,4-butanediol for PBS. Several dimers and trimers i.e. hydroxybutyl adipate, hydroxybutyl succinate, di(hydroxybutyl) adipate, di(hydroxybutyl) succinate and hydroxybutyl disuccinate were also detected. Best extraction efficiency for 1,4-butanediol and succinic acid was achieved with a hydroxylated polystyrene-divinylbenzene resin as solid phase. Linear range for the extracted analytes was 1-500 ng/ml for adipic acid and 2-500 ng/ml for 1,4-butanediol and succinic acid. Detection and quantification limits for all analytes were between 1-2 ng/ml (S/N=3) and 2-7 ng/ml (S/N=10) respectively. Relative standard deviations were between 3 % and 7 %. Comparison of measured weight loss and the amount of monomeric products showed that weight loss during early stages of hydrolysis was mainly caused by the release of water-soluble oligomers that on prolonged ageing were further hydrolyzed to monomeric species. Significant differences in degradation rate could be assigned to degree of branching, molecular weight, aging temperature and degradation medium.</p><p>Linear and branched PBA was mixed with PVC in solution cast films to study the effects of molecular weight and branching on plasticizer efficiency. Used as polymeric plasticizer, PBA formed a semi-miscible two-phase system with PVC where the amorphous part exhibited one single glass transition temperature and the degree of polyester crystallinity was dependent on molecular weight, degree of branching and blend composition. Plasticizing efficiency was favored by higher degree of branching and a 40 weight-percent polyester composition.</p>

Este trabalho objetivou o desenvolvimento e validação de métodos analíticos para determinação de fexofenadina em cápsulas e comprimidos revestidos e o estudo de fotoestabilidade do fármaco. A determinação da faixa de fusão e a espectrofotometria no infravermelho permitiram identificar fexofenadina substância química de referência. Os métodos por cromatografia em camada delgada, espectrofotometria no ultravioleta (UV), cromatografia líquida de alta eficiência (CLAE) e eletroforese capilar (EC) foram utilizados para análise qualitativa do fármaco nas formas farmacêuticas. A determinação quantitativa foi realizada através da validação dos métodos por UV e CLAE para cápsulas e comprimidos e EC para cápsulas, avaliando-se os parâmetros descritos pelas guias de validação. Os métodos propostos não apresentaram diferença estatística para um nível de significância de 1%. O teste de dissolução foi desenvolvido e validado utilizando HCl 0,01 M como meio de dissolução, cestas a 100 rpm e pás a 75 rpm para cápsulas e comprimidos revestidos, respectivamente. Perfis de dissolução de cápsulas dos medicamentos referência e similar e comprimidos revestidos dos medicamentos referência, similar e genérico foram realizados e comparados através dos fatores de diferença e semelhança e da eficiência de dissolução e não apresentaram-se semelhantes. Estudo preliminar de estabilidade de fexofenadina frente à degradação ácida, alcalina, oxidativa, térmica e fotolítica mostrou a oxidação e a luz como fatores importantes de degradação. A cinética de fotodegradação de fexofenadina em soluções metanólica e aquosa demonstrou cinética de segunda ordem de reação. A estabilidade acelerada da fexofenadina foi realizada utilizando-se soluções metanólicas pH=6 e pH=11, as quais foram expostas às lâmpadas metal haleto e UVC 254 nm, havendo formação dos produtos majoritários, denominados PD-21 e PD-37, os quais foram isolados por cromatografia em coluna e CCD preparativa. A fotólise do pó de comprimidos e de comprimidos demonstrou haver formação dos mesmos produtos de degradação obtidos em solução. Os produtos foram identificados por ressonância magnética nuclear e espectrometria de massas como derivados benzofenona (PD-21) e isopropílico (PD-37) da fexofenadina. / The aim of this study was the development and validation of analytical methods to the determination of fexofenadine in capsules and coated tablets and the photostability study of the drug. The melting range determination and infrared spectrophotometry allowed fexofenadine standard reference identification. Methods of thin-layer chromatography (TLC), ultraviolet spectrophotometry (UV), high performance liquid chromatography (HPLC), and capillary electrophoresis (CE) were employed to the qualitative analysis of the drug in pharmaceutical formulations. The quantitative determination was performed through the validation of UV and HPLC for capsules and coated tablets, and CE for capsules, evaluating the guidances validation parameters. The proposed methods were not statistically different to a 1% significance level. The dissolution test was developed and validated using HCl 0,01 M as dissolution medium, basket at 100 rpm and paddle at 75 rpm to capsules and coated tablets, respectively. Dissolution profiles of reference and similar capsule products and reference, similar and generic coated tablets products were performed and compared using difference factor, similarity factor and the dissolution efficiency, showing not similarity. Preliminary stability study of fexofenadine through acid, alkaline, oxidative, thermal, and photolytic degradation shows sensibility to oxidation and light. The kinetic of photodegradation of fexofenadine in methanol and water solutions show second order kinetic of reaction. The accelerated stability was evaluated using fexofenadine methanolic solutions pH=6 and pH=11, which were exposed to a metal halide lamp and to a fluorescent lamp UVC 254 nm, giving two majority degradation products, assigned PD-21 and PD-37. The separation was carried out by HPLC and TLC. The products were isolated by column chromatography and preparative TLC techniques. The analysis of the powder of tablets and tablets, which were exposed to light, showed the same degradation products presented for solutions. The majority degradation products of fexofenadine were identified by nuclear magnetic resonance and mass spectrometry as a benzophenone derivative (PD-21) and isopropyl derivative (PD-37).