In dieser Arbeit wird eine neue Methode und ein neuartiges FET -Sensorelement zum Nachweis von Flüssigkeitsbewegungen vorgestellt, das zudem bei Bedarf auch als Chemo- oder Biosensor fungieren kann. Das Einsatzspektrum von FET-basierten Sensoren in Lab on a Chip-Systemen wird dadurch entscheidend erweitert. Bei dem entwickelten FET-Sensor Bauelement handelt es sich um einen normally-on n-leitenden Dünnschichtfeldeffekttransistor mit Ti-Au-Kontakten, basierend auf Silicon-on-Insulator- Substraten, wobei das natürliche Oxid des Siliziumfilms als Schnittstelle zum Elektrolyten bzw. zur Flüssigkeit verwendet wird. Der mit 10exp16 Bor Atomen pro cm³ p-dotierte Siliziumdünnfilm hat eine Dicke von nur 55 nm und ist durch eine 95 nm dicke Siliziumdioxidschicht vom darunterliegenden Siliziumsubstrat von 600 µm Dicke elektrisch isoliert. Aufgrund der geringen Schichtdicke durchdringt die feldempfindliche Raumladungs- bzw. Verarmungszone die gesamte Dünnschicht, so dass durch Anlegen einer Backgatespannung am Substrat der spezifische Widerstand und die Empfindlichkeit des Bauelements eingestellt werden können. Grundlegende ISFET-Funktionalitäten wie die Empfindlichkeit auf Änderungen der Ionenstärke und des pH-Wertes werden nachgewiesen und ein ENFET-Glukosesensor realisiert. Zudem wird im Hinblick auf die Separation von Emulsionen der Nachweis erbracht, dass die Benetzung mit Hexan und Toluol eine Änderung der spezifischen Leitfähigkeit bewirkt, und die Empfindlichkeit des Bauelements nach Beschichtung mit einem hydrophoben Methacrylatcopolymerfilm erhalten bleibt. Hinsichtlich der Verwendung des FET-Sensor Bauelements zum Nachweis von Flüssigkeitsbewegungen wird zunächst ein theoretisches Modell entwickelt, dessen Kernaussage ist, dass sich in einem rechteckigen Kanal der relative Bedeckungsgrad mit Flüssigkeit direkt proportional zum Drainstrom des FET-Sensors verhält. Basierend auf diesem theoretischen Modell, welches experimentell belegt wird, können mittels eines einzelnen FET-Sensors Füllstand und Füllgeschwindigkeit bzw. bei bekannter Füllgeschwindigkeit Kapillarvolumen und Kapillargeometrie bestimmt werden. Abweichungen von der direkten Proportionalität erlauben zudem, Rückschlüsse auf die Benetzungseigenschaften der Kapillaren und die Dynamik an der Halbleitergrenzfläche zu ziehen. Ist ein Sensorelement vollständig mit Flüssigkeit bedeckt, wird mittels Lösungsmitteltropfen als Markerobjekten die Strömungsgeschwindigkeit bestimmt. Ändert sich die Ionenkonzentration im Elektrolyten als Funktion der Strömungsgeschwindigkeit, so kann die Strömungsgeschwindigkeit durch Messung der Ionenkonzentration mittels FET-Sensor ebenfalls ermittelt werden. Als wichtigster Demonstrator für die Verwendung des FET-Sensors wird ein komplexes Lab on a Chip-System zur Separation von Emulsionen auf chemisch strukturierten Oberflächen entwickelt, bei dem der Separationsvorgang mittels FET-Sensorarray verfolgt werden kann. Zur einfachen Herstellung chemisch modifizierter Oberflächen für die Separationsexperimente werden die Abscheidung von nanoskaligen hydrophoben Methacrylatcopolymerfilmen und die selektive Fluorsilanisierung von Oberflächen sowie deren Lösungsmittelbeständigkeit in Wasser, Toluol und Aceton untersucht. Dabei zeigt sich, dass die Hydrophobie nach Lösungsmittelbehandlung weitestgehend erhalten bleibt, Wasserrückstände im Methacrylatfilm aber zu einer reversiblen Schichtdegradation führen können. Als Modellsystem werden Hexan-Wasser- bzw. Toluol-Wasser-Emulsionen verwendet, die auf Oberflächen getrennt werden, deren eine Seite hydrophil, und deren andere Seite hydrophob ist (Stufengradient). Der Separationsprozess beruht auf der großen Affinität des Wassers hin zu polaren Oberflächen, wobei das wenig selektive Lösungsmittel zur unpolaren Seite gedrängt wird. Zur Erlangung eines tieferen Verständnisses des Prozesses werden die Tropfenkoaleszenz und der Einfluss geometrischer Beschränkungen untersucht. Die Versuche werden sowohl auf offenen Oberflächen als auch im Spalt, unter Verwendung von hydrophilen und hydrophoben Oberflächen, durchgeführt. Es zeigt sich, dass sich die Dynamik der Tropfenkoaleszenz im Spalt umgekehrt zur Dynamik auf offenen Oberflächen verhält. Dies wird mittels eines hierzu entwickelten theoretischen Modells erklärt, welches die Minimierung der Oberflächenenergie und Hystereseeffekte einbezieht. Das Lab on a Chip-System schließlich besteht aus einem mit Siliziumnitrid beschichteten FET-Sensorchip, auf den eine Separationszelle aufgeklebt ist. Neben dem Einlass für die Emulsion ist ein weiterer Einlass vorhanden, durch den Salzsäure für eine pH-Reaktion zugegeben werden kann. Der gesamte Separationsprozess sowie die anschließende pH-Reaktion, lassen sich bequem am PC anhand der Änderung der Stromstärke der einzelnen Sensoren verfolgen und analysieren. Wichtige Ergebnisse hier sind: 1) Mittels eines quasi 1-dimensionalen Sensorarrays kann der Verlauf einer Flüssigkeitsfront in einem 2-dimensionalen Areal überwacht bzw. dargestellt werden. 2) Anhand der Signatur des Signalverlaufs bei pH-Änderung und Flüssigkeitsbewegung, können beide Prozesse unterschieden werden. Der Sensor kann also zum Nachweis von Flüssigkeitsbewegungen und zugleich als Chemosensor eingesetzt werden. Es wurde also nicht nur ein neuartiges, äußerst robustes, chemikalienbeständiges und biokompatibles Multifunktionssensorelement mit Abmessungen im Mikrometer- bis Millimeterbereich entwickelt, sondern auch eine neue Methode entwickelt, mit der es möglich ist, sowohl (bio-)chemische Reaktionen als auch die Bewegung von Flüssigkeiten in Lab on a Chip-Systemen nachzuweisen.

Cold mix asphalt (CMA) emulsion technology could become an attractive option for the road industry as it offers lower startup and equipment installation costs, energy consumption and environmental impact than traditional alternatives. The adhesion between bitumen and aggregates is influenced by diverse parameters, such as changes in surface free energies of the binder and aggregates or the presence of moisture or dust on the surface of aggregates, mixing temperatures, surface textures (including open porosity), nature of the minerals present and their surface chemical composition, as well as additives in the binder phase. The performance of cold asphalt mixtures is strongly influenced by the wetting of bitumen on surfaces of the aggregates, which is governed by breaking and coalescence processes in bitumen emulsions. Better understanding of these processes is required. Thus, in the work this thesis is based upon, the surface free energies of both minerals/aggregates and binders were characterized using two approaches, based on contact angles and vapor sorption methods. The precise specific surface areas of four kinds of aggregates and seven minerals were determined using an approach based on BET (Brunauer, Emmett and Teller) theory, by measuring the physical adsorption of selected gas vapors on their surfaces and calculating the amount of adsorbed vapors corresponding to monolayer occupancy on the surfaces. Interfacial bond strengths between bitumen and aggregates were calculated based on measured surface free energy components of minerals/aggregates and binders, in both dry and wet conditions. In addition, a new experimental method has been developed to study bitumen coalescence by monitoring the shape relaxation of bitumen droplets in an emulsion environment. Using this method, the coalescence of spherical droplets of different bitumen grades has been correlated with neck growth, densification and changes in surface area during the coalescence process. The test protocol was designed to study the coalescence process in varied environmental conditions provided by a climate-controlled chamber. Presented results show that temperature and other variables influence kinetics of the relaxation process. They also show that the developed test procedure is repeatable and suitable for studying larger-scale coalescence processes. However, possible differences in measured parametric relationships between the bitumen emulsion scale and larger scales require further investigation. There are several different research directions that can be explored for the continuation of the research presented in this thesis. For instance, the rationale of the developed method for analyzing coalescence processes in bitumen emulsions rests on the assumption that the results are applicable to large-scale processes, which requires validation. A linear relationship between the scales is not essential, but it is important to be able to determine the scaling function. Even more importantly, qualitative effects of the investigated parameters require further confirmation. To overcome the laboratory limitations and assist in the determination of appropriate scaling functions further research could focus on the development of a three-dimensional multiphase model to study coalescence processes in more detail, including effects of surfactants, pH and other additives such as mineral fillers and salts. Additionally, better understanding of the breaking process and water-push out could help significantly to optimize CMA mix design. Different methods, both numerical and experimental could be explored for this. / Cold mix asphalt (CMA) eller kall asfaltbetong med hjälp av emulsionsteknik kan vara ett attraktivt alternativ för vägbyggnadsindustrin då det möjliggör lägre uppstart- och investeringskostnader, lägre energiförbrukning och mindre miljöpåverkan än traditionella alternativ. Adhesionen mellan bindemedel och stenpartiklarna påverkas av ett flertal parametrar, så som förändring i fri ytenergi hos både bindemedel och partiklar i närvaro av fukt eller damm på stenytorna, blandningstemperatur, yttextur (inklusive ytporositet), mineralegenskaper och ytornas kemiska sammansättning lika väl som tillsatsmedel i bindemedlen. Beteendet hos kall asfaltbetong är starkt påverkad av vätningsegenskaperna hos bindemedlet när det kommer i kontakt med stenmaterialet och detta i sin tur är beroende på bitumenemulsionens brytegenskaper och förmåga att blandas. Bättre förståelse av dessa processer är av största vikt. I detta arbete är avhandlingen baserad på fri ytenergi hos både mineraler/aggregat och bindemedel, baserat på kontaktvinkel och på ångabsorptionsmetoder. Den exakta specifika ytan hos fyra typer av aggregat och sju mineraler undersöktes med en metod baserad på BET (Brunauer, Emmett och Teller):s teorier genom att mäta den fysiska adsorptionen av utvalda gaser på ytorna och beräkna mängden adsorberad ånga som korresponderade mot ytlagret. Styrkan hos kontaktytornas bindning mellan bindemedlet och stenaggregaten beräknades baserat på mätningar av den fria ytenergin hos bägge ingående komponenterna, dels i torrhet dels i våta omgivningar. Som tillägg har en ny experimentell metod utvecklats för att studera bitumens blandbarhet genom att studera bitumendroppars relaxation i en emulsionsmiljö. Genom att använda denna metod har korelationen mellan sväriska droppar av bitumen undersökts mot förändringen i ytans area under blandningsprocessen. Testprotokollet utformades för att studera blandningsprocessen i varierande miljöer i en klimatkammare. Presenterade resultat visar att temperatur och andra variabler påverkar de kinetiska förhållandena vid relaxationsprocessen. De visar även att den utvecklade testmetoden är repeterbar och passar för studier av storskaliga blandningsprocesser. Det bör dock påpekas att vidare studier krävs för att påvisa skillnaderna mellan bitumenemulsionsskalan och större skalor. Framtida forskning kommer att koncentreras på utveckling av tredimensionella multifas­modeller för att studera blandningsförlopp på en mer detaljerad nivå, inkluderande effekter på ytaktiva ämnen, pH-värden och andra additativ så som mineralfiller och salt. Som tillägg kommer nyttan av nya karaktäriseringsmetoder att utvärderas, så som lågvikelspridning av neutroner eller kombinationer av röntgen, neutronradiologi och datortomografi, för att studera brytmekanismer hos bitumenemulsioner vid kontakt med mineraler och aggregat. / <p>QC 20160901</p>

Cadre conceptuel et problématique : La cholestase hépatique est une pathologie à large éventail d’étiologies, affectant fréquemment les nouveau-nés. Un diagnostic approprié est essentiel pour la prise en charge clinique, le choix des traitements et l’amélioration du pronostic. Alors que les prématurés ont un risque accru de développement de la cholestase, les algorithmes de traitement ne proposent qu’une prise en charge unique, quel que soit l’âge gestationnel (AG) du patient. Objectif : Déterminer si le profil clinique, la prise en charge et le pronostic de la cholestase néonatale diffèrent selon l’AG. Méthodologie : Une étude de cohorte rétrospective de nouveau-nés atteints de cholestase et admis en néonatologie au CHU Sainte Justine entre janvier 2014 et décembre 2017 a été menée. La cholestase était définie par au moins deux valeurs consécutives de bilirubine conjuguée ≥ 34 μmol/L. La cohorte a été stratifiée en deux groupes d’AG : les extrêmes et les grands prématurés (< 32 semaines AG) et les prématurés modérés ou tardifs et naissances à terme (≥ 32 semaines AG). Résultats : 125 nouveau-nés sur 3 277 ont développé une cholestase. L’incidence globale était de 4% ; cette incidence était 5 fois plus élevée chez les nouveau-nés < 32 semaines d’AG comparativement aux ≥ 32 semaines d’AG. La cholestase était associée à une nutrition parentérale chez 91% des patients avec AG < 32 semaines et seulement 40% des patients avec AG ≥ 32 semaines (p < 0,01). Alors que l'acide ursodésoxycholique était plus prescrit aux nouveau-nés ≥ 32 semaines AG, les émulsions lipidiques à base d'huile de poisson étaient plus administrées aux nouveau-nés < 32 semaines AG, parmi les patients recevant une nutrition parentérale. Conclusion : La cholestase néonatale est associée à deux profils cliniques différents, basés sur l'AG. Nous recommandons que les tests diagnostics et la prise en charge clinique de la cholestase soient adaptés à l'AG. Une nouvelle approche pour l'évaluation d'un nourrisson atteint d'hyperbilirubinémie conjuguée est proposée. / Background and Aims: Cholestasis is a frequent neonatal disease that has a wide range of etiologies. Appropriate diagnosis is essential to clinical management, treatment choices and improvement of outcomes. Most references discuss neonatal cholestasis as one entity. The goal of this study was to determine if the clinical profile, management and outcome of cholestasis differ according to gestational age (GA). Methods: Medical records of infants with cholestasis in the division of neonatology at CHU Sainte Justine, between January 2014 and December 2017, were retrospectively reviewed. Cholestasis was defined as two or more consecutive conjugated bilirubin values ≥ 34μmol/L. The cohort was stratified into two groups: extremely to very preterm (< 32 weeks GA) and moderate to late preterm and term (≥ 32 weeks GA). Results: 125 of 3,277 patients developed cholestasis. Overall incidence of cholestasis was 4%. Incidence was 5 times higher in neonates < 32 weeks GA compared to neonates ≥ 32 weeks GA. Cholestasis was associated with parenteral nutrition in 91% of patients with GA < 32 weeks and 40% of patients with GA ≥ 32 weeks (p < 0.01). While ursodiol treatment was prescribed more to cholestatic neonates ≥ 32 weeks GA, fish oil lipid was administered more to neonates < 32 weeks GA, among patients receiving parenteral nutrition. Conclusions: Neonatal cholestasis was associated with two different clinical profiles based on GA. We recommend diagnostic tests and clinical management of neonatal cholestasis be adapted to GA. A GA-based approach to the evaluation of an infant with conjugated hyperbilirubinemia is proposed.

Die vorliegende Arbeit beschreibt Herstellungsmöglichkeiten für sogenannte Saturn-Partikel. Es handelt sich dabei um Partikel, die auf ihrer Oberfläche drei Bereiche mit unterschiedlichen Eigenschaften aufweisen. Zwei Kappen mit gleichen Eigenschaften sind durch einen Gürtel getrennt, der sich stark von den Kappen unterscheidet. Im Speziellen geht es hier um die unterschiedliche Benetzbarkeit der Bereiche. Die Herstellung von Saturn-Partikeln mit einem hohen Benetzungskontrast wurde auf zwei verschiedenen Wegen realisiert. Als Ausgangspunkt dienten Mikroglaskugeln, die zunächst zur Hydrophobierung ihrer Oberfläche mit einem Silan behandelt wurden. Eine Art der Saturn-Partikel wurde durch das Ätzen eines Gürtels rund um die Partikel mit Flusssäure in einer im Rahmen dieser Arbeit entwickelten Spülzelle erzeugt. Auf diese Weise konnten Partikel mit zwei hydrophoben Kappen und einem hydrophilen Gürtel erhalten werden. Eine weitere Art dieser Partikel wurde durch das Abschleifen der Partikelkappen nach vorheriger Einbettung in Polymerfilme erhalten, wodurch die hydrophobe Beschichtung abgetragen und das ursprünglich hydrophile Glas freigelegt wurde. Die so erhaltenen Partikel wiesen zwei parallele, hydrophile Bereiche auf, die durch einen hydrophoben Gürtel voneinander getrennt waren. Es wird gezeigt, dass Saturn-Partikel in Systemen mit Wasser und Öl beim Mischen von unterschiedlichen Anteilen der drei Phasen durch Selbstorganisationsprozesse verschiedene Strukturen wie Ketten oder Schichten ausbilden können. Des Weiteren sind sie in der Lage in einem System mit Wasser und Luft besondere Schäume auszubilden, die eine sehr hohe Stabilität aufweisen. Die Partikel stabilisieren darin Flüssigkeitsfilme zwischen den Luftblasen, wobei der hydrophile Gürtel im Wasserfilm und die hydrophoben Kappen in der Luft liegen.

No / Sedimentation of non-homogeneous systems is the typical phenomenon indicating the physical instability as a key measure to the quality control of the preparation products. Currently, the determination methods for the sedimentation of non-homogeneous preparations are based on manual measurement or semi-quantitative observation, lacking of either automation or quantitative dynamic analysis. The purpose of this research was to realize automatic and quantitative monitoring of the sedimentation dynamics for non-homogenous systems as suspension, emulsions at laboratory level. Non-contact measurement method has been established to determine the sedimentation behaviors in a standard quartz tube for sedimentation, with internal diameter and height 23 mm and 215 mm, respectively, with controlled temperature and light intensity. As high performance camera has been equipped, the sedimentation images with high spatial and temporal resolution could be acquired, which can continuously capture sedimentation images with the resolution of 2048 x 2048 pixel at a maximum rate of 60 slides/s. All the pictures were processed to extract the luminance matrix top-down along the fixed vertical midline of each picture, which implied sedimentation characteristics of the system at the moment the picture was taken. Combining all the luminance matrixes along vertical middle lines of the pictures, a time-luminance matrix profile was obtained. Digital image processing techniques were used to eliminate interference and establish a three-dimensional surface model of the sedimentation dynamics. Then, the derivative mutation algorithm has been developed for the intelligent identification of sedimentation interface with threshold optimization so as to quantitatively analyze the sedimentation dynamics with visualization. The sedimentation curve and sedimentation dynamic equation of the non-homogeneous system were finally outputted by numerical fitting. The methodology was validated for great significance in determinations of small volume samples, parallel control multiple batches, and long period of time automatic measurement. (C) 2015 Elsevier B.V. All rights reserved.

No / PURPOSE: Self-emulsifying systems (SES) emulsify spontaneously to produce fine oil-in-water emulsion when introduced into aqueous phase. The self-emulsification process plays an important role during formation of emulsion. The objective of current work was to understand and explore the inner structuration of SES through controlled hydration and further to study the influence of additive on the same which ultimately governs performance of final formulation in terms of droplet size. METHODS: Droplet size of final formulations containing structural analogues of ibuprofen was determined. Microstructural properties of intermediate hydrated regimes of SES were investigated using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology. RESULTS: The current work established inverse relationship between droplet size of the formulations containing structural analogues of ibuprofen and their Log P values. Microstructural analysis of intermediate hydrated regimes of the prepared samples showed formation of local lamellar structure. Structural analogues of ibuprofen significantly altered microstructure of lamellae which was well correlated with the droplet size of final formulations. In vitro drug release study showed increase in dissolution rate of lipophillic drugs when formulated as SES. CONCLUSION: The current work emphasizes the fact that tailor-made formulations can be prepared by controlling the properties of intermediate regimes.

Self-emulsifying systems are mixtures of oils and surfactants, ideally isotropic, sometimes including cosolvents, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastrointestinal tract. The process of self-emulsification has remained the center of attraction for most researchers. Controlled hydration of self-emulsifying systems shows formation of an intermediate gel phase which upon rupture forms an emulsion. Current work was undertaken to understand and explore the microstructural properties of intermediate gel phase which are believed to influence the performance (droplet size) of the final formulation. The effect of additives on microstructural properties of intermediate gel phase has also been investigated. Microstructural elucidation of hydrated samples of intermediate regimes was done by using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology. Samples from intermediate regimes showed formation of local lamellar structure which swelled with hydration. In the present work, the effect of addition of salt form of naproxen (sodium and potassium) and naproxen (base) on microstructural properties of intermediate regimes was investigated. Systems containing naproxen salts formed larger droplets whereas naproxen base formed smaller ones. Microstructural properties of intermediate lamellar structures were well correlated with performance of the final formulation. The current studies indicate that by controlling the properties of intermediate regimes optimized formulations with desired performance can be tailor-made.

L'objectif de la thèse était d'étudier la mobilité de traceurs particulaires dans des milieuxcomplexes par microscopie confocale à balayage laser (CLSM) combinée avec le suivi demultiple particules (MPT) et le recouvrement de fluorescence après photoblanchiment (FRAP).Tout d'abord, nous avons étudié la diffusion de particules dans les gels formés par des protéinesglobulaires. Dans ce but, des gels avec structures variés ont été préparés en faisant varier lesconcentrations en protéine et en sel. La structure a été caractérisée par l'analyse des imagesobtenues par CLSM en termes de fonction de corrélation de paires. La mobilité de particulesavec une large gamme de tailles (2nm - 1 micron) a été étudiée à la fois dans des gels homogèneset hétérogènes et reliée à la structure du gel.Deuxièmement, nous avons étudié des émulsions eau dans eau préparées en mélangeant dessolutions aqueuses de PEO et de dextran. Il a été montré que lorsque des particules colloïdalessont ajoutées, elles sont emprisonnées à l'interface eau-eau, car elles réduisent la tensioninterfaciale. La structure et le déplacement des particules à l'interface ont été déterminés parCLSM combinée avec MPT. / The objective of the thesis was to investigate the mobility of tracer particles in complex media byConfocal Laser Scanning Microscopy (CLSM) combined with multiple particle tracking (MPT)and fluorescence recovery after photobleaching (FRAP).First, we investigated the diffusion of tracer particles in gels formed by globular proteins. Gelswith a variety of structures were prepared by varying the protein and salt concentrations. Thestructure was characterized by analysis of the CLSM images in terms of the pair correlationfunction. The mobility of particles with a broad range of sizes (2nm - 1μm) was investigatedboth in homogeneous and heterogeneous gels and related to the gel structure.Second, we studied water-in-water-emulsions prepared by mixing aqueous solutions of PEO anddextran. It is shown that when colloidal particles are added they become trapped at the waterwaterinterface because they reduce the interfacial tension. The structure and the displacement ofthe particles at the interface were determined using CLSM combined with MPT.

A rutina é empregada como antioxidante e na prevenção da fragilidade capilar. Pode ser veiculada em emulsões tópicas adequadas para atingir o local de ação. Estudos de penetração in vitro através da pele humana seria a situação ideal, entretanto, há dificuldades de sua obtenção e manutenção de sua viabilidade. Entre os demais modelos de membrana, a muda de pele de cobra apresenta-se como estrato córneo puro, fornecendo barreira similar ao humano e é obtida sem a morte do animal. Os objetivos desta pesquisa foram: (1) desenvolver e avaliar a estabilidade de emulsões cosméticas, contendo rutina e promotores de penetração cutânea, tais como, uréia (U), isopropanol (IP) e propilenoglicol (PG); (2) avaliar a liberação da referida substância ativa das emulsões e; (3) avaliar a penetração e a retenção cutânea in vitro da rutina da formulação de melhor desempenho. Emulsões foram desenvolvidas com rutina a 5,0% p/p e U, IP e PG, associados ou não e em proporções distintas, segundo planejamento fatorial com dois níveis com ponto central. Quantificou-se a rutina das emulsões por espectrofotometria a 361,0 nm, método previamente validado. A liberação da rutina nas formulações foi realizada em células de difusão vertical com membrana de acetato de celulose e água destilada e álcool etílico absoluto 99,5% (1:1), como fluido receptor. O experimento foi conduzido em um período de seis horas, a 37,0 ±. 0,5 &#176;C e agitação constante de 300 rpm.>f. emulsão de melhor desempenho quanto à liberação foi estudada quanto à estabilidade (Testes de Estabilidade Acelerada). Para o estudo de penetração e retenção cutânea da rutina dessa formulação foi utilizada muda de pele de cobra de Crotalus durissus. Empregou-se o método espectrofotométrico validado a 410,0 nm para a quantificação da rutina após liberação, penetração e retenção cutânea. Todas as emulsões foram consideradas adequadas após desenvolvimento das formulações. A uréia (isolada e em associação com IP e PG) e o isopropanol (isolado e em associação com PG) influenciaram negativamente a liberação da rutina das emulsões em diversos parâmetros. A rutina liberada e acumulada da formulação contendo PG a 5,0% p/p possuiu valor de 648,80 ±. 53,01 &#181g/cm2. Fora do esperado, a preparação contendo o número maior de promotores (U 5,0% p/p, IP 5,0% p/p e PG 5,0% p/p) resultou em liberação de menor magnitude igual a 419,76 ±. 17,98 &#181g/cm2. A presença do PG apresentou-se mais eficiente na liberação da rutina, mas não na sua penetração através da muda de pele de C. durissus, retendo 0,931 ± 0,0391 &#181;g de rutina/mg de muda de pele de cobra. Nas condições de armazenamento a 25,0 ±2,0 &#176;C; 5,0 ±0,5 &#176;C e 45,0 ±. 0,5 &#176;C, a emulsão com PG e rutina apresentou-se quimicamente estável durante 30 dias. De acordo com os resultados, a emulsão contendo PG apresentou liberação mais expressiva da rutina, no entanto, não ocorreu a penetração cutânea, mas apenas sua retenção no estrato córneo de C. durissus. A preparação manteve-se estável em todas as condições de armazenamento. / Rutin is employed as antioxidant and to prevent the capillary fragility and, when incorporated in cosmetic emulsions, it must target the action site. In vitro cutaneous penetration studies through human skin is the ideal situation, however, there are difficulties to obtain and to maintain this tissue viability. Among the membrane models, the shed snake skin presents itself as pure stratum corneum, providing barrier function similar to human and it is obtained without the animal sacrifica. The objectives of this research were: (1) development and stability evaluation of cosmetic emulsions containing rutin and penetration enhancers, as urea (U), isopropanol (IP) and propylene glycol (PG); (2) release evaluation of the mentioned active substance from the emulsions and; (3) evaluation of rutin in vitro cutaneous penetration and retention from the emulsion of the best performance. Emulsions were developed with rutin 5.0% w/wand U, IP and PG, associated or not according to factorial design with two levels and central point. Active substance on the formulations was quantified by a validated spectrophotometric method at 361.0 nm. Rutin release from emulsions was performed in vertical diffusion cells with cellulose acetate membrane and distilled water and ethanol 99.5% (1:1), as receptor fluid. The experiment was conducted for six hours, at 37.0 ± 0.5 °c with constant stirring of 300 rpm. Formulation with best profile of rutin release had its stability studied by the Accelerated Stability Assays. Rutin cutaneous penetration and retention from the mentioned emulsion was performed with shed snake skin from Crotalus durissus. Spectrophotometry at 410.0 nm, previously validated, determined the active substance after release and cutaneous penetration/retention. Ali emulsions were considered apparently stables after development. Urea (isolated and associated with IP and PG) and isopropanol (isolated and associated with PG) have influenced negatively the rutin release in several parameters. Emulsion with PG 5.0% w/w presented rutin released and accumulated equal to 648.80 ± 53.01 &#181;g/cm2. Unexpectedly, the formulation containing all enhancers (U 5.0% w/w, IP 5.0% w/w and PG 5.0% w/w) has decreased the amount released of the active substance (419.76 ± 17.98 &#181;g/cm2). Emulsion with PG presented more adequate for rutin release, but PG did not provide rutin cutaneous penetration through C. durissus skin, retaining 0.931 ± 0.0391 &$181;g rutin/mg shed snake skin. The referred formulation was chemically stable for 30 days after they have been stored at 25.0 ± 2.0 &#176;c, 5.0 ± 0.5 &#176;c and 45.0 ± 0.5 &#176;C. In conclusion, emulsion with PG provided rutin release more expressively, although, it has not been verified the active cutaneous penetration, but only its retention on the Crotalus durissus stratum corneum. Formulation was stable in all storage conditions.

A hidrolipodistrofia ginóide, popularmente denominada de celulite, é caracterizada como um processo distrófico que produz alterações estruturais dos elementos presentes na pele, como: modificações no tecido conjuntivo, comprometimento da microcirculação periférica cutânea, hipertrofia e hiperplasia dos adipócitos e edema. Os flavonóides são utilizados como substâncias ativas em preparações anticelulíticas por reduzirem a permeabilidade capilar. Os objetivos estabelecidos para esta pesquisa foram: (1) desenvolver emulsões cosméticas com finalidades anticelulíticas; (2) validar metodologia analítica para o doseamento de flavonóides totais, equivalentes em rutina, por espectrofotometria na região do ultravioleta; (3) avaliar a estabilidade física, físico-química e química das formulações. Formulações cosméticas anticelulíticas foram desenvolvidas contendo o extrato vegetal comercial de Trichilia catiguá Adr. Juss (e) Ptychopetalum olacoides Bentham (Slimbuster® H1), padronizado em flavonóides totais, equivalentes em rutina, e avaliadas quanto à estabilidade física, físico-química e química. Para sua quantificação, o método espectrofotométrico na região do ultravioleta a 361,0 nm foi empregado, comparando-se com rutina padrão secundário de referência (T = 96,1%). A avaliação da estabilidade envolveu três condições distintas de temperatura (5,0 + 0,5; 24 + 2 e 40,0 + 0,5 &#176;C), pelo período de três meses, e as variáveis analisadas foram as características organolépticas, valor de pH, viscosidade aparente e teor de flavonóides totais. A metodologia foi validada quanto à linearidade, limites de detecção e quantificação, especificidade e pesquisa de interferentes, recuperação do padrão, precisão e exatidão intra e inter-dias. Os resultados da estabilidade indicaram que o teor de flavonóides totais, equivalentes em rutina, sofreu decaimento inferior a 10% nas condições de exposição à luz solar direta e/ou indireta, à temperatura ambiente (24 + 2 &#176;C) e de refrigerador (5,0 + 0,5 &#176;C), sendo que a 40,0 + 0,5 &#176;C, condição de estufa, ocorreu redução de, aproximadamente, 35%. / Gynoid hydrolipodystrophy, popularly known as cellulite, is characterized as a dystrophic process that generates structural alterations of skin elements, as: connective tissue modifications, cutaneous microcirculation abnormalities, hypertrophy and hyperplasia of adipocytes and edema. Flavonoids are employed as raw materials in anticellulitic products by their capability to reduce capillary permeability. The objectives established for this research were: (1) development of anticellulitic cosmetic emulsions; (2) analytical method validation for total flavonoids, expressed in rutin, by ultraviolet spectrophotometry; (3) physical, physicochemical and chemical stability assay for the preparations. Anticellulitic cosmetic formulations containing the Trichilia catigua Adr. Juss (and) Ptychopetalum olacoides Bentham commercial extract (Slimbuster® H1), standardized in total flavonoids, expressed in rutin, were developed and their physical, physicochemical and chemical stability was assessed. Flavonoids were quantified within the ultraviolet spectrophotometric method at 361.0 nm as rutin equivalents by comparison with secondary standard rutin (T = 96.1%). Stability assay was conducted in three temperature conditions (5.0 + 0.5; 24 + 2 e 40.0 + 0.5 &#176;C) and the following parameters were analyzed: aspect, color and odor, pH and apparent viscosity values and flavonoid content. Analytical methodology was validated determining linearity, limits of detection and quantification, specificity and interferent assay, recovery and intra and inter-run precision and accuracy. Results from stability evaluation have indicated decrease of flavonoid content inferior than 10% at sunlight exposure (room temperature, 24 + 2 &#176;C) and at 5.0 + 0.5 &#176;C; high temperature (40.0 + 0.5 &#176;C) has reduced the flavonoid content at, approximately, 35%.