In dieser Arbeit wird die Herstellung und spektroelektrochemische Charakterisierung von Polymeren aus alkylsubstituierten Anilinderivaten beschrieben. Hierzu wird die zyklische Voltammetrie sowie als in situ-spektroskopische Methoden UV-vis-, FTIR- und Raman-Spektroskopie eingesetzt. Aus allen eingesetzten Monomeren lassen sich elektroaktive und elektrochrome Polymere herstellen. Bei der Mehrzahl der Polymere konnten in situ-Leitfähigkeitsmessungen durchgeführt werden, die eine intrinsische, vom Elektrodenpotential abhängige elektrische Leitfähigkeit zeigen. Der molekulare Aufbau innerhalb der Polymerketten wird durch FTIR- und Raman-Spektroskopie in Analogie zum Polyanilin identifiziert. Er ist wie beim Polyanilin vom Oxidationsgrad abhängig.

In dieser Arbeit wird die Herstellung und spektroelektrochemische Charakterisierung von Polymeren aus alkylsubstituierten Anilinderivaten beschrieben. Hierzu wird die zyklische Voltammetrie sowie als in situ-spektroskopische Methoden UV-vis-, FTIR- und Raman-Spektroskopie eingesetzt. Aus allen eingesetzten Monomeren lassen sich elektroaktive und elektrochrome Polymere herstellen. Bei der Mehrzahl der Polymere konnten in situ-Leitfähigkeitsmessungen durchgeführt werden, die eine intrinsische, vom Elektrodenpotential abhängige elektrische Leitfähigkeit zeigen. Der molekulare Aufbau innerhalb der Polymerketten wird durch FTIR- und Raman-Spektroskopie in Analogie zum Polyanilin identifiziert. Er ist wie beim Polyanilin vom Oxidationsgrad abhängig.

Actualment està creixent molt l'ús de sistemes d'alliberament controlat de fàrmacs en la indústria farmacèutica ja que aquests permeten alentir la seva velocitat d'alliberament, i a la vegada permeten reduir el nombre de dosis sense arribar a nivells tòxics plasmàtics.Aquestes propietats són de gran interès i no s'obtenen amb els medicaments tradicionals que podem trobar comercialment. Aquests sistemes estan formats generalment per un principi actiu i una matriu polimèrica responsable de la modulació de la velocitat d'alliberament del fàrmac.Aquesta tesi doctoral està dividida en dues parts: en primer lloc, la preparació de diferents sistemes d'alliberament controlat utilitzant tecnologies supercrítiques que impliquen l'ús de CO2. Aquests processos supercrítics es consideren tecnologies netes, ja que es proposen com a alternativa de les tècniques convencionals que utilitzen solvents orgànics. Així doncs, s'han elaborat diversos sistemes d'alliberament dels següents fàrmacs model: el triflusal, la 5-azacitidina, el naproxèn i el ketoprofèn. Els polímers escollits com a transportadors de fàrmacs són biodegradables o biològicament compatibles i està aprovat el seu ús en humans i en aplicacions in vivo.En segon lloc, s'han determinar les característiques fisicoquímiques d'aquests sistemes mitjançant tècniques analítiques adequades. Aquestes característiques inclouen la determinació morfològica de les mostres a nivell macroscòpic i la determinació de les temperatures característiques dels sistemes polimèrics per comprovar la possible dispersió dels fàrmacs a nivell molecular. Les tècniques utilitzades han estat la microscòpia confocal de rastreig (SEM), la microscòpia confocal de fluorescència i la calorimetria diferencial d'escombratge (DSC). També s'han desenvolupat mètodes en flux continu amb detecció UV i de cromatografia de líquids amb detecció UV i de florescència per al seguiment de les diferents cinètiques d'alliberament i la determinació de les quantitats de fàrmac en cada mostra preparada.S'ha fet especial èmfasi en l'estudi del fàrmac antineoplàstic 5-azacitidina ja que és molt inestable en solucions aquoses. S'han estudiat les característiques àcid-base del fàrmac i la seva estabilitat en funció del pH i la temperatura per tenir-ne un coneixement previ abans de recobrir-lo amb la matriu polimèrica de PLA. Els diferents estudis cinètics, termodinàmics i àcid base s'han resolt mitjançant la utilització de mètodes de resolución multivariant de corbes per mínims quadrats alternats (MCR-ALS). La estabilitat in vitro de la 5-azacitidina ha millorat considerablement gràcies a la protecció que li proporciona el polímer.S'han estudiat els sistemes preparats en els diferents medis en que es pretén que siguin alliberats. Així, els de via oral s'han estudiat a valors de pH del tracte gastrointestinal, és a dir, de l'estómac i l'intestí. Aquells tòpics o transdèrmics s'han estudiat a valors de pH pròxims als de la pell mitjançant l'ús de cel·les de difusió de Franz. Com ja s'ha comentat en el paràgraf anterior, s'ha focalitzat l'interès en la millora de l'estabilitat d'aquests sistemes en les noves formulacions amb matrius protectores.Els sistemes d'alliberament de fàrmacs han estat preparats satisfactoriamente mitjançant diferents tècniques supercrítiques. En els diversos sistemes estudiats s'han observat comportaments diferenciats en l'alliberament, però sempre corresponents al tipus d'aplicació a la qual van destinats. Les quantitats de fàrmacs impregnats o recoberts han estat elevades. A més a més, s'ha observat també la dispersió a nivell molecular dels fàrmacs en totes les matrius polimèriques implicades. / Nowadays the use of drug delivery systems in the pharmaceutical industry is growing since these provide control over the rate of drug release. This and other properties of great interest are not obtained when drugs are administered in conventional dosage forms. These systems are made of an active ingredient and a polymeric matrix responsible for the modulation of the rate of drug delivery.This thesis is divided into two parts: firstly, the preparation of some controlled release systems using supercritical CO2 technologies. These supercritical processes are considered clean technologies to be used as an alternative of conventional techniques using organic solvents. Thus, several drugs were selected as model compounds: triflusal, 5-azacytidine, naproxen and ketoprofen. The polymers chosen as drug carriers were biodegradable or biologically compatible.Secondly, the physicochemical properties of these systems were determined through suitable analytical techniques. These properties included the investigation of macroscopic morphology and the determination of characteristic temperatures of the polymeric systems. The used techniques were: scanning electron microscopy (SEM), confocal fluorescence microscopy and differential scanning calorimetry (DSC). Continuous flow methods with UV detection and HPLC-DAD and HPLC-FLD methods were also developed for the monitoring of release kinetics and the determination of drug amounts in each prepared sample.Special emphasis was laid on the study of 5-azacytidine since its high instability in aqueous solutions. Its acid-base properties and its stability depending on pH and temperature were studied to have a previous knowledge before coating it with L-PLA polymeric matrix. Several kinetic, thermodynamic and acid-base studies were solved through the use of Multivariate Curve Resolution-Alternated Least Squares (MCR-ALS). Moreover, in vitro 5-azacytidine stability was improved considerably thanks to polymer protection.The systems prepared were followed in different environments simulating physiological body conditions. Aims were focused on the stability improvement of these new formulations with protective polymeric matrices. Drug delivery systems were prepared successfully through several supercritical techniques. Different behaviours of the systems studied were observed. High amounts of impregnated or coated drugs were obtained. Besides, the dispersion at molecular level of the drugs was also observed in all the polymeric systems studied.

Heidelberg, Univ., Diss., 2008.

Tübingen, Univ., Diss., 2006.

Zugl.: Stuttgart, Univ., Diss., 2008

Regensburg, Univ., Diss., 2005.

Made available in DSpace on 2014-06-11T19:23:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-11-19Bitstream added on 2014-06-13T18:09:41Z : No. of bitstreams: 1 storti_fc_me_bauru.pdf: 1104117 bytes, checksum: f3374b86db01b726a613c1cc13d060e9 (MD5) / Nesta dissertação é apresentado um estudo envolvendo a arquitetura molecular (crescimento controlado, morfologia e organização molecular) de filmes Layer-by-Layer (LbL) contendo ftalocianina tetrasulfonada de cobre (CuTsPc). Inicialmente foram realizados estudos sobre a cinética de crescimento desses filmes para determinação do tempo de adsorção do material no substrato. Uma vez determinado este tempo, filme LbL foram fabricados utilizando soluções catiônica de poli(alilamina) hidroclorada - PAH) e aniônica de CuTsPc. Os filmes de PAH/CuTsPc foram produzidos de forma manual e utilizando um braço mecânico em valores de pHs 2,5; 5,5 e 8,5 sendo então caracterizados por espectroscopia eletrônica via absorção na região do ultravioleta-visível (UV-Vis), espectroscopia vibracional via espalhamento Raman e absorção na região do infravermelho com transformadora de Fourier (FTIR) e microscopias óptica e força atômica (AF,A). A espectroscopia de absorção na região do UV-Vis foi utilizada para acompanhar o crescimento do filme LbL assim como investigar a presença de agregados. A técnica de FTIR permitiu investigar as interações entre o PAH e a CuTsPc e determinar a organização molecular comparando filme LbL e cast. O acoplamento entre microscópio óptico e espectrógrafo Raman (técnica microRaman) possibilitou analisar a morfologia do filme LbL em escala micrométrica combinando informações ópticas e químicas. A morfologia do filme LbL em escala nanométrica foi investigada utilizando-se AFM. Foi observado que os filmes crescidos mecanicamente são mais espessos em relação aos crescidos manualmente, além de apresentarem maior rugosidade. Ainda em termos morfológicos, os filmes crescidos mecanicamente apresentam uma maior quantidade de agregados, porém, menores em termos de diâmetro médio, tanto em escala nano como micrométrica... / This dissertation presents a study involving the molecular architecture (controlled growth, morphology, and molecular organization) of layer-by-layer (LbL) films containing copper phthalocyanine tetrasulfonated (CuTsPc). Initially, the studies were performed on the kinetics of growth of these films to determine the time of adsorption of the material on the substrate. Once determined this time, LbL films were produced by using solutions of cationic poly (hydrochloric alilamina - PAH) and anionic CuTsPc. The films of PAH / CuTsPc were produced either manually or using a mechanical arm in pH values of 2.5, 5.5, and 8.5, and then characterized by electron spectroscopy via absorption in the ultraviolet-visible (UV-Vis), vibrational spectroscopy by Raman scattering and absorption in the infrared region with Fourier transform infrared (FTIR) and optical microscopy and atomic force microscopy (AFM). The absorption spectroscopy in the UV-Vis was used to follow the growth of the LbL film and to investigate the presence of aggregates. The FTIR technique allowed investigatin the interactions between the PAH and CuTsPc and determining the molecular organization comparing LbL films and cast. The coupling between optical microscope and Raman spectrograph (micro-Raman technique) allowed analyzing the morphology of the LbL film at micrometric scale combining optical and chemical information. The morphology of the LbL film at nanometer scale was investigated by using AFM. It was observed that the films grown mechanically are thicker in relation to grown manually and present greater roughness. Also in morphological terms, the films grown mechanically have an increased number of aggregates, however, smaller in terms of average diameter, at nano and micrometric scales. It was found that the pH is a key parameter to induce the formation of molecular clusters. For instance, more homogeneous LbL films in term... (Complete abstract click electronic access below)

Orientador: Carlos José Leopoldo Constantino / Banca: Marystela Ferreira / Banca: Luciana Gaffo / O Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, PosMat, tem caráter institucional e integra as atividades de pesquisa em materiais de diversos campi da Unesp / Resumo: Nesta dissertação é apresentado um estudo envolvendo a arquitetura molecular (crescimento controlado, morfologia e organização molecular) de filmes Layer-by-Layer (LbL) contendo ftalocianina tetrasulfonada de cobre (CuTsPc). Inicialmente foram realizados estudos sobre a cinética de crescimento desses filmes para determinação do tempo de adsorção do material no substrato. Uma vez determinado este tempo, filme LbL foram fabricados utilizando soluções catiônica de poli(alilamina) hidroclorada - PAH) e aniônica de CuTsPc. Os filmes de PAH/CuTsPc foram produzidos de forma manual e utilizando um braço mecânico em valores de pHs 2,5; 5,5 e 8,5 sendo então caracterizados por espectroscopia eletrônica via absorção na região do ultravioleta-visível (UV-Vis), espectroscopia vibracional via espalhamento Raman e absorção na região do infravermelho com transformadora de Fourier (FTIR) e microscopias óptica e força atômica (AF,A). A espectroscopia de absorção na região do UV-Vis foi utilizada para acompanhar o crescimento do filme LbL assim como investigar a presença de agregados. A técnica de FTIR permitiu investigar as interações entre o PAH e a CuTsPc e determinar a organização molecular comparando filme LbL e cast. O acoplamento entre microscópio óptico e espectrógrafo Raman (técnica microRaman) possibilitou analisar a morfologia do filme LbL em escala micrométrica combinando informações ópticas e químicas. A morfologia do filme LbL em escala nanométrica foi investigada utilizando-se AFM. Foi observado que os filmes crescidos mecanicamente são mais espessos em relação aos crescidos manualmente, além de apresentarem maior rugosidade. Ainda em termos morfológicos, os filmes crescidos mecanicamente apresentam uma maior quantidade de agregados, porém, menores em termos de "diâmetro médio", tanto em escala nano como micrométrica... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This dissertation presents a study involving the molecular architecture (controlled growth, morphology, and molecular organization) of layer-by-layer (LbL) films containing copper phthalocyanine tetrasulfonated (CuTsPc). Initially, the studies were performed on the kinetics of growth of these films to determine the time of adsorption of the material on the substrate. Once determined this time, LbL films were produced by using solutions of cationic poly (hydrochloric alilamina - PAH) and anionic CuTsPc. The films of PAH / CuTsPc were produced either manually or using a mechanical arm in pH values of 2.5, 5.5, and 8.5, and then characterized by electron spectroscopy via absorption in the ultraviolet-visible (UV-Vis), vibrational spectroscopy by Raman scattering and absorption in the infrared region with Fourier transform infrared (FTIR) and optical microscopy and atomic force microscopy (AFM). The absorption spectroscopy in the UV-Vis was used to follow the growth of the LbL film and to investigate the presence of aggregates. The FTIR technique allowed investigatin the interactions between the PAH and CuTsPc and determining the molecular organization comparing LbL films and cast. The coupling between optical microscope and Raman spectrograph (micro-Raman technique) allowed analyzing the morphology of the LbL film at micrometric scale combining optical and chemical information. The morphology of the LbL film at nanometer scale was investigated by using AFM. It was observed that the films grown mechanically are thicker in relation to grown manually and present greater roughness. Also in morphological terms, the films grown mechanically have an increased number of aggregates, however, smaller in terms of "average diameter", at nano and micrometric scales. It was found that the pH is a key parameter to induce the formation of molecular clusters. For instance, more homogeneous LbL films in term... (Complete abstract click electronic access below) / Mestre

Dietary food supplements are among the most rapidly growing sectors in the food product industry. The majority of consumers trust in the safety and efficacy of these products. For these reasons is a quality control required and analytical methodologies for this must be used. For identification and quantitative analysis four flavonoids diosmin, hesperidin, rutin and troxerutin in food supplements was used HPLC/MS method. For identification and quantitative analysis three carotenoids betacarotene, lutein and zeaxanthin in food supplements was used HPLC/UV/ViS/DAD method. Separation of flavonoids was achieved on the column ZORBAX POROSHELL 120 EC-C18 (50 x 4,6 mm, 2,7 um) and separation of carotenoids on the column ZORBAX SB CN (75 x 4,6 mm, 3,5 um). The amount of flavonoids and carotenoids in tablets and capsules was determined altogether in 12 different commercial preparations.