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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Drug nanosizing using microfluidic reactors. Development, characterisation and evaluation of corticosteroids nano-sized particles for optimised drug delivery.

Ali, Hany S.M. January 2010 (has links)
Over recent years the delivery of nanosized drug particles has shown potential in improving bioavailability. Drug nanosizing is achieved by ¿top-down¿ and by ¿bottom-up¿ approaches. Owing to limitations associated with the top-down techniques, such as high energy input, electrostatic effects, broad particle size distributions and contamination issues, great interest has been directed to alternative bottom up technologies. In this study, the hypothesis that microreactors can be used as a simple and cost-effective technique to generate organic nanosized products is tested using three steroids (hydrocortisone, prednisolone and budesonide). Arrested antisolvent nanoprecipitation using ethanol (solvent) and water (antisolvent) was conducted within the microreactors. To enable experimental design for the microreactor studies, solubility profiles in different ethanol-water combinations at 25 °C were explored. All three drugs¿ solubility increased with increasing ethanol concentration showing maxima at 80-90 % v/v ethanol-water mixtures. Because of the complex multivariate microfluidic process, artificial neural network modelling was then employed to identify the dominant relationships between the variables affecting nanoprecipitation (as inputs) and the drug particle size (as output). The antisolvent flow rate was found to have the major role in directing drug particle size. Based on these successful findings, the potential of preparing pharmaceutical nanosuspensions using microfluidic reactors was researched. A hydrocortisone (HC) nanosuspension (NS) was prepared by introducing the generated drug particles into an aqueous solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system was then used to concentrate the prepared NS. Results showed that a stable narrow sized HC NS of amorphous spherical particles 500 ± 64 nm diameter and zeta potential ¿18 ± 2.84 mV could be produced. The ocular bioavailability of a microfluidic precipitated HC NS (300 nm) was assessed and compared to a similar sized, milled HC NS and HC solution as a control. The precipitated and the milled NS achieved comparable AUC0-9h of 28.06 ± 4.08 and 30.95 ± 2.2, respectively, significantly (P < 0.01) higher than HC solution (15.86 ± 2.7). These results illustrate the opportunity to design sustained release ophthalmic formulations. Going nano via microfluidic precipitation was also exploited to tailor budesonide (BD) NS for pulmonary administration. The in vitro aerosolization by nebulization of a BD NS was studied in comparison with a commercial BD microsuspension. Overall, the fine particle fraction generated from BD NS (56.88 ± 3.37) was significantly (P < 0.05) higher than the marketed BD (38.04 ± 7.81). The mean mass aerodynamic diameter of BD NS aerosol (3.9 ± 0.48 ¿m) was significantly smaller (P < 0.05) than the microsuspension (6.2 ± 1.09 ¿m) indicating improved performance for BD NS. In conclusion, findings of this study support the hypothesis of using microfluidic nanoprecipitation as a promising and economical technique of drug nanosizing. / Egyptian Government (Ministry of High Education)
12

Immunmodulation autologer Tissue-Engineering-Transplantate in vivo

Wanjura, Frank 07 October 2002 (has links)
Im medizinischen Alltag steht Gewebeersatz oftmals nicht ausreichend zur Verfügung. Tissue Engineering (TE) bietet eine wertvolle Methode, um aus wenigen Zellen des gewünschten Gewebes größere Strukturen herzustellen. Aber selbst autologe über Tissue Engineering gebildete Gewebe können einer Abstoßung unterliegen. Diese Arbeit befaßt sich daher mit der Immunmodulation von TE-Transplantaten. Chondrocyten wurden aus Ohrknorpel von Neuseeland-Kaninchen enzymatisch isoliert, in Zellkultur vermehrt und wurden a) in allogenem Fibrinkleber oder b) in Agarose suspendiert, dann in ein Scaffold eingebracht. 24 Transplantate wurden zusätzlich mit einer Polyelectrolyt Kapsel versehen. Nativer Ohrknorpel diente als Kontrolle. So entstanden n=84 Transplantate, 14 autologe Transplantate pro Kaninchen: jeweils 2 native, 4 Fibrin-, 4 Agarose- und 4 Kapsel-Transplantate. Die 1cm x 1cm x 0.2 cm großen Transplantate wurden subkutan auf dem Rücken der Kaninchen implantiert. Eine der in zwei Gruppen aufgeteilten Kaninchen erhielt eine 3 wöchige i. m. Gabe von Methylprednisolon. 70 Transplantate wurden in 5 Versuchstiere implantiert. 14 Transplantate wurden in vitro ernährt. 2 Kaninchen wurden nach 6 Wochen getötet und die Transplantate entnommen. 3 Kaninchen wurden nach 12 Wochen getötet. Im Anschluß wurden die Transplantate histologisch untersucht. Die Transplantate der nicht immunmodulierten Tiere konnten zu den Entnahmezeitpunkten 6 und 12 Wochen kaum aus den Implantationsorten entnommen werden: sie waren nur schwer vom umliegenden Gewebe zu unterscheiden. Die Transplantate der immunmodulierten Tiere blieben in ihrer Größe konstant. Histologisch zeigte sich bei den nicht immunmodulierten Tieren nach 6 Wochen massive zelluläre Infiltration, nach 12 Wochen die Einwachsung von Fibrozyten und kaum noch Knorpel- oder Knochengewebe. In der Gruppe der immunmodulierten Tiere konnte keine bis eine geringe Inflammation festgestellt werden. Bis auf die nativen Transplantate, war in dieser Gruppe bei allen Transplantaten vitaler trabekulärer Knochen mit hämatopoetisch aktivem Knochenmark zu beobachten. Der Vergleich der Gruppen Nicht immunmoduliert und Immunmoduliert war hinsichtlich der Immunreaktionen statistisch signifikant (Chi-Quadrat Test nach Pearson). / Tissue replacement is a common need in clinical medicine. And often there is too less tissue available. Tissue Engineering (TE) is a valuable measure to solve this problem: only a few cells of the origin tissue are cultivated and new threedimensional structures are built. But even autologeously built tissues can be rejected by the host. Therefore, this investigation is about immunomodulation of TE-transplants. Chondrocytes of ear cartilage of New Zealand rabbits were enzymatically isolated, amplified and were solved in a) allogenic fibrin glue or b) agaraose. Then they were taken into scaffolds. 24 transplants were encapsulated by a polyelectrolyte-complex membrane. Native cartilage served as control. There were formed n=84 transplants, 14 autologeous transplant per rabbit: each with 2 native, 4 fibrin-, 4 agarose- and 4 capsule-transplants. The tranplants size was 1 cm x 1 cm x 0.2 cm. The rabbits were divided into two groups one of the group has been treated with methylprednisolone IM for 3 weeks. 70 transplants were taken into the ridge of 5 rabbits. 14 transplants were cultivated in vitro. 2 rabbits were sacrificed after 6 weeks and 3 rabbits after 12 weeks. Afterwards the transplants were investigated histologically. The transplants of the non-immunomodulated group could hardly be separated from the surrounding tissue, whereas the transplants of the immunomodulated group remained constant in seize and shape. Histologically, the non-immunomodulated tranplants underwent cellular (granulocytes) infiltration after 6 weeks, respectively ingrowth of fibrocytes after 12 weeks. No cartilage or bone could was evident. In the immunomodulated group no signs of inflammation were identifiable after 6 and 12 weeks. In all transplants of this group bone formation with hematopoietically-active bone marrow was detectable. The native control-cartilage had not become bone, inflammation wasnot evident there. The difference of the two groups non-immunomodulated and immunomodulated was statistically significant concerning th degree of inflammation. (Chi-square-test).
13

Medical Treatment and Grading of Bell's Palsy

Berg, Thomas January 2009 (has links)
The main aim of this thesis was to evaluate the effect of prednisolone and valaciclovir in a large number of Bell's palsy patients. The incidence and intensity of pain around the ear, in the face or in the neck during the first two months of palsy, and its prognostic value, was also assessed. We also investigated how study design and choice of analysis method affect the rate of facial recovery. Furthermore, the agreement between the Sunnybrook, House-Brackmann and Yanagihara facial grading systems was evaluated. From May 2001 to September 2007, a prospective, randomised, double-blind, placebo-controlled, multicentre trial with 12-month follow-up was performed in patients with Bell's palsy. Of 839 randomised patients, 829 were included in the intention-to-treat analysis; 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 who did not (p&lt;0.0001). At 12 months, 300 of 416 patients (72%) in the prednisolone group had recovered compared with 237 of 413 patients (57%) in the no prednisolone group (p&lt;0.0001). Valaciclovir was not found to affect time to facial recovery or outcome at 12 months. Prednisolone and/or valaciclovir did not affect the incidence or intensity of pain. Presence of pain at day 11 to 17 indicated a worse prognosis for facial recovery at 12 months. We also found that recovery rates in a Bell's palsy trial are substantially affected by the choice of analysis method and definition of facial recovery. We used weighted Kappa statistics in 100 examinations of patients with facial palsy to assess the agreement between the Sunnybrook, House-Brackmann and Yanagihara scales. The highest agreement was found between the regional Sunnybrook and Yanagihara scales. An evaluative difference between the Sunnybrook and House-Brackmann systems was observed.
14

The screening of anti-inflammatory action of Clinacanthus nutans (Burm. f.) Lindau : a critical evaluation of carrageenan-induced hind paw edema model /

Wipa Tanasomwang, Jutamaad Satayavivad, January 1986 (has links) (PDF)
Thesis (M.Sc. (Pharmacology))--Mahidol University, 1986.
15

Estudo comparativo do uso de betabloqueador e corticosteroide oral no tratamento do hemangioma infantil / Comparative study of the use of beta-blocker and oral corticosteroid in the treatment of infantile hemangioma

Hiraki, Patricia Yuko 08 November 2017 (has links)
INTRODUÇÃO: Hemangioma Infantil (HI) é o tumor vascular mais comum da infância. Em 1992 a International Society for the Study of Vascular Anomalies (ISSVA) definiu o hemangioma infantil como tumor benigno de células endoteliais, com características clínicas, radiológicas e imuno-histoquímicas específicas. A origem do HI ainda é desconhecida. É sabido que apresentam potencial involutivo espontâneo e que o tratamento é indicado em 10% a 20% dos casos, podendo ter caráter emergencial ou eletivo. As indicações emergenciais compreendem situações de ameaça à função ou vida. As indicações eletivas são reservadas aos casos de hemangiomas localizados em áreas que podem levar à deformidade e/ou cicatriz permanente, quando apresentam complicações locais ou pequenas lesões em áreas expostas, podendo o tratamento ser clínico ou cirúrgico. A terapêutica medicamentosa tem sido a rotina e historicamente a opção mais utilizada foi o corticosteroide, cuja a eficácia é variável e os eventos adversos são frequentes. Em 2008 uma descoberta fortuita introduziu os betabloqueadores como nova opção para o tratamento do HI, com resultados estáveis e posteriores evidências clínicas do benefício da droga no tratamento do HI. Neste contexto, propôs-se avaliar o uso do propranolol, quantificando sua eficácia, segurança e incidência de eventos adversos, comparando-se ao uso da prednisolona (PRED). MÉTODO: Estudo intervencionista prospectivo randomizado com 50 portadores de HI, atendidos no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Os pacientes selecionados tinham idade inferior a 2 anos e indicação eletiva de tratamento. Os indivíduos incluídos foram aleatoriamente alocados em 2 grupos, sendo o primeiro grupo de tratamento com prednisolona e o outro de tratamento com propranolol (PROP), ambos por via oral, por 2 meses. Os pacientes foram seguidos semanalmente para mensuração de parâmetros clínicos incluindo peso, pressão arterial (PA), frequência cardíaca (FC) e saturação de oxigênio, além de avaliação objetiva da ocorrência de eventos adversos. A resposta ao tratamento foi avaliada de forma quantitativa por meio de medidas diretas da lesão e por 3 avaliadores independentes segundo critérios de melhora do aspecto clínico geral, volume, cor e envolvimento funcional. Os eventos adversos foram avaliados quanto a sua incidência e gravidade, utilizando-se a classificação do Common Terminology Criteria for Adverse Events. RESULTADOS: Vinte e seis pacientes foram alocados no grupo PRED e 24 no grupo PROP. Da casuística 37 indivíduos completaram as 8 semanas de seguimento. Em 8 casos houve interrupção precoce do tratamento em função de eventos adversos, em 1 caso por falha terapêutica e em 4 casos houve perda de seguimento. A idade média no grupo PRED foi de 6,46 meses e no grupo PROP de 7,25 meses. O gênero feminino foi predominante em ambos os grupos. A face foi a localização anatômica mais acometida, seguido do tronco. A resposta ao tratamento foi efetiva e sem distinção entre os grupos, com redução significativa das medidas avaliadas. Quanto as avaliações clínicas de acordo com o coeficiente de correlação interclasses, houve concordância interna excelente entre os avaliadores. As notas atribuídas para os pacientes mostraram melhora com o tratamento e no quesito cor mostrou-se diferença significativa em favor do grupo PROP. Quanto aos parâmetros clínicos mensurados, o percentil de peso mostrou elevação progressiva no grupo PRED sendo a diferença significativa em relação ao grupo PROP. A diferença nas medidas de PA sistólica entre os grupos foi significativa e a análise multivariável evidenciou uma elevação significativa no grupo PRED ao passo que no grupo PROP não houve alteração dos níveis pressóricos. A avaliação da FC revelou um significativo declínio no grupo PROP na 6º semana, não se mantendo no restante do período. Não foram identificadas alterações nas medidas de saturação de oxigênio. Quanto a incidência os eventos adversos (EA) a diferença entre os grupos foi significativa. No grupo PRED 22 pacientes apresentaram 35 EA sendo os mais frequentes o aspecto cushingoide, elevação da PA e infecções. No grupo PROP 10 pacientes apresentaram 10 EA incluindo hipotensão e distúrbios respiratórios. Quando a gravidade dos EA foi avaliada não foram observadas diferenças. CONCLUSÃO: Prednisolona e propranolol foram igualmente efetivos em reduzir o tumor. Considerando-se os eventos adversos, o uso do propranolol se mostrou como tratamento mais tolerável em relação ao uso do corticosteroide / INTRODUCTION: Infantile hemangioma (HI) is the most common vascular tumor of childhood. In 1992 the International Society for the Study of Vascular Anomalies (ISSVA) defined infantile hemangioma as a benign endothelial cell tumor with specific clinical, radiological and immunohistochemical characteristics. The origin of HI is still unknown. It is known that they have spontaneous involutive potential and that the treatment is indicated in 10% to 20% of the cases, and it can be emergency or elective. Emergency indications include life threatening situations. Elective indications are reserved for cases of hemangiomas located in areas that may lead to permanent deformity and/or scarring, when they present local complications or small lesions in exposed areas, and this treatment may be clinical or surgical. Drug therapy has been the routine and historically the most widely used option was the corticosteroid, whose efficacy is variable and the adverses events are frequent. In 2008 a fortuity finding introduced beta-blockers as a new option for HI treatment, with stable results and subsequent clinical evidence of drug benefit in the treatment of HI. In this context, it was proposed to evaluate the use of propranolol, quantifying its efficacy, safety and incidence of adverse events, compared to the use of prednisolone. METHODS: Prospective randomized interventional study with 50 patients with HI from the \"Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo\". The patients selected were younger than 2 years and had an elective indication of treatment. Patients included were randomly allocated into 2 groups, the first group being treated with predinisolone (PRED) and the other with propranolol (PROP), both orally, for 2 months. Patients were followed weekly to measure clinical parameters including weight, blood pressure (BP), heart rate (HR) and oxygen saturation, as well as an objective evaluation of the occurrence of adverse events. The response to treatment was quantitatively assessed by means of direct measures of the lesion and by 3 independent evaluators according to criteria of improvement of general clinical appearance, volume, color and functional involvement. Adverse events were evaluated for their incidence and severity, using the classification of the Common Terminology Criteria for Adverse Events. RESULTS: Twenty-six patients were allocated to the PRED group and 24 to the PROP group. Overall, 37 patients completed the 8-week follow-up. In 8 cases there was an early interruption of treatment due to adverse events, in 1 case due to therapeutic failure and in 4 cases there was loss of follow-up. The mean age in the PRED group was 6.46 months and in the PROP group of 7.25 months. The female gender was predominant in both groups. The face was the most affected anatomic location, followed by the trunk. The treatment response was effective and without distinction between groups, with a significant reduction of the measures evaluated. Regarding the clinical evaluations according to the interclass correlation coefficient, there was excellent internal agreement among the evaluators. The scores attributed to the patients showed improvement with the treatment and in the item color there was a significant difference in favor of the PROP group. Regarding the clinical parameters measured, weight percentile showed progressive elevation in the PRED group, presenting significant difference in relation to the PROP group. The difference in systolic BP measurements between groups was significant and multivariate analysis showed a significant increase in the PRED group, whereas in the PROP group there was no change in pressure levels. The HR evaluation revealed a significant decline in the PROP group in the 6th week, not remaining in the remainder of the period. No changes in oxygen saturation measurements were identified. Regarding the incidence and adverse events (AE), the difference between the groups was significant. In the PRED group 22 patients presented 35 AEs, the most frequent being cushingoid appearance, elevated BP and infections. In the PROP group 10 patients presented 10 AEs including hypotension and respiratory disorders. When the severity of AE was assessed, no differences were observed. CONCLUSION: Prednisolone and propranolol were equally effective in reducing the tumor. Considering the adverse events, the use of propranolol was shown as a more tolerable treatment in relation to corticosteroid use
16

"Ensaio clínico controlado randomizado aberto com metil-prednisolona em portadores de mielopatia associada ao HTLV-1 paraparesia espástica tropical" / Clinical controlled randomized open trial with methylprednisolone in myelopathy associated to HTLV-1 / tropical spastic paraparesis

Tauil, Carlos Bernardo 23 March 2004 (has links)
Estudamos a avaliação clínica de longo termo da resposta de pacientes com diagnóstico precoce de HAM/TSP ao tratamento com metil-prednisolona. Objetivamos pesquisar em relação ao tempo de evolução e apresentação da doença a eficácia deste tratamento. Realizamos o acompanhamento dos pacientes utilizando como parâmetros as escalas de critérios clínicos de Osame e Kurtzke e comparamos com um grupo controle que não recebeu este tipo de tratamento.Os pacientes do grupo experimental e do grupo controle que realizaram fisioterapia mantiveram-se estáveis ou obtiveram melhora de alguns sintomas da doença / We studied the long-term clinical response of patients with early diagnoses of HAM/TSP to treatment with methylprednisolone. The aim was to study this treatment in relation to the time of evolution and presentation of the disease and its effectiveness. The patients were followed using the scales of clinical criteria by Osame and Kurtzke, and compared with a control group of patients who did not receive this treatment type. We observed that patients in the experimental group and the control group, having been followed up with physiotherapy, either remained stable or presented improvement for some symptoms of the disease
17

"Quantificação da força muscular e habilidades motoras de pacientes com distrofia muscular de Duchenne, em tratamento com corticoterapia" / Quantification of muscular strength and motor hability of the patients with Duchenne muscular dystrophy, in steroides therapy

Parreira, Samara Lamounier Santana 19 September 2005 (has links)
Em 32 pacientes com Distrofia Muscular de Duchenne, em corticoterapia, avaliou-se a evolução da força muscular, ao longo de 14 meses, mensalmente no primeiro semestre e a cada dois meses no segundo e terceiro semestre. Testes empregados: escala "Medical Research Council", Hammersmith "motor ability score", levantamento de peso cronometragem do tempo para manobra de Gowers e para percorrer 9 metros. O estudo revelou tendência de estabilidade da força muscular durante o acompanhamento e que para avaliar objetivamente a força muscular são suficientes intervalos de três meses no primeiro semestre de corticoterapia e, posteriormente, de seis meses enquanto durar o tratamento / In 32 patients with Duchenne muscular dystrophy and receiving steroid therapy we assessed muscle strength along a follow-up of 14 months using Medical Research Council scale, Hammersmith functional motor scale, timed testing for rising from the floor and walking 9 meters, as well as rising weights. The tests were repeated monthly along the first 6 months and every two months by the rest of the follow-up. The study revealed a trend to functional stability and that the muscle strength can be evaluated at 3 and 6 months of treatment and then every 6 months while the steroid therapy is maintained
18

Einfluss von unterschiedlichen immunsuppressiven Strategien auf Proliferation, Stoffwechsel und Differenzierung humaner fetaler neuraler Progenitorzellen in vitro

Glien, Anja 26 February 2015 (has links) (PDF)
The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro.
19

Nanocápsulas de núcleo lipídico : estudos de penetração cutânea e proposição de estratégias para a avaliação da liberação in vitro / Lipid-core nanocapsules: cutaneous penetration studies and proposition of strategies to assess the in vitro drug release

Andrade, Diego Fontana de January 2013 (has links)
Neste trabalho foi avaliada a permeação/penetração cutânea in vitro (pele suína) de propionato de clobetasol nanoencapsulado incorporado em um semissólido, empregando células de difusão de Franz. A nanoencapsulação foi capaz de reduzir a quantidade de fármaco que penetra nas camadas da pele (estrato córneo, epiderme e derme) sem alterar a forma (distribuição percentual) como o propionato de clobetasol se distribui. A adequabilidade de diferentes membranas sintéticas (acetato de celulose, policarbonato e membrana de diálise) para a avaliação da liberação in vitro, empregando células de difusão de Franz, a partir desta formulação foi também estudada. A partir da combinação de diferentes técnicas analíticas (espalhamento de luz dinâmica, microscopias eletrônicas de transmissão e varredura) foi observado que a membrana de menor tamanho de poro (membrana de diálise, 12 kDa de cut off) é a mais adequada para a condução deste tipo de avaliação, pois é a única capaz de evitar a passagem de nanocápsulas íntegras da formulação para o meio receptor das células de difusão, em detrimento das membranas de policarbonato e acetato de celulose (0,05 μm e 0,45 μm de tamanho de poro, respectivamente). Além disso, uma nova estratégia para a avaliação da liberação in vitro de fármacos associados a nanocápsulas de núcleo lipídico, combinando fluxo contínuo de meio de liberação e sacos de diálise foi proposta neste trabalho. A técnica mostrou-se adequada para a obtenção do perfil de liberação in vitro a partir de suspensões de nanocápsulas contendo diferentes fármacos modelo (prednisolona e propionato de clobetasol), possibilitando a diferenciação destes sistemas de soluções contendo os fármacos livres, graficamente e pelos valores de fluxo calculados. Adicionalmente, esta estratégia mostrou-se apropriada para a manutenção da concentração de fármaco no meio de liberação afastada da saturação, contribuindo para o atendimento da condição sink. Ainda, classificamos o sistema como um protótipo semi-automatizado para a avaliação da liberação in vitro de fármacos, capaz de gerar resultados com maior precisão em relação à diálise convencional. / The in vitro cutaneous permeation/penetration (porcine skin) of clobetasol propionate-loaded lipid-core nanocapsules incorporated into a semisolid dosage form was evaluated, using the Franz diffusion cells technique. It was shown that the nanoencapsulation was able to reduce the drug amount penetration into skin layers (stratum corneum, epidermis and dermis) without changing the way (percentual distribution) that it was distributed. The suitability of different synthetic membranes (cellulose acetate, polycarbonate, and dialysis membrane) to assess the in vitro drug release using Franz diffusion cells from this formulation was also studied. It was ascertained by combining different analytical techniques (dynamic light scattering, scanning and transmition electron microscopy) that the membrane with smaller pore size (dialysis membrane, 12 kDa cut off) is the most appropriate for conducting this kind of study, because it is the only one able of preventing the passage of intact nanocapsules from formulation to Franz diffusion cells receptor media, instead of polycarbonate and cellulose acetate membranes (0.05 and 0.45 pore size, respectively). In addition, a new strategy to assess in vitro drug release drug-loaded lipid-core nanocapsules was proposed, associating continuous flow of release media and dialysis sac. The proposed system was adequate to assess the in vitro drug release profiles from nanocapsule suspensions containing different model drugs (prednisolone and clobetasol propionate), enabling the differentiation of these systems from drug solutions, graphically and by the calculated flux values. Furthermore, this strategy was suitable to maintain the drug concentration into release media far away from saturation, contributing to the sink condition. Also, the proposed system was described as a semi-automated prototype for in vitro drug release evaluation, able to produce results with greater accuracy than conventional dialysis technique.
20

[en] DEVELOPMENT OF A PHOTOCHEMICAL DERIVATIZATION PROCEDURE FOR TWO SYNTHETIC GLUCOCORTICOIDS (PREDNISOLONE AND TRIAMCINOLONE ACETONIDE) AIMING THE SPECTROFLUORIMETRIC ANALYSIS OF PHARMACEUTICAL FORMULATIONS / [pt] DESENVOLVIMENTO DE PROCEDIMENTO DE DERIVATIZAÇÃO FOTOQUÍMICA PARA DOIS GLICOCORTICÓIDES SINTÉTICOS (PREDNISOLONA E TRIANCINOLONA ACETONIDO) VISANDO À ESPECTROFLUORIMÉTRICA DE FORMULAÇÕES FARMACÊUTICAS

ANETE LOPES COELHO 08 April 2005 (has links)
[pt] Os glicocorticóides sintéticos tais como a triancinolona acetonido e a prednisolona não possuem fluorescência natural e nem são induzidos a fluorescer por meio do procedimento padrão para glicocorticóides naturais, que consiste no tratamento com ácido sulfúrico concentrado. No presente trabalho, um procedimento de derivação fotoquímica para triancinolona acetonido e prednisolona foi desenvolvido e cuidadosamente otimizado com o intuito de se obter derivados fluorescentes estáveis que permitiram elaborar um método espectrofluorimétrico para determinação dos mesmos em formulações farmacêuticas. Este procedimento consistiu na exposição à radiação ultravioleta (300 nm) de soluções ácidas dos glicocorticóides sintéticos em reator fotoquímico. Parâmetros experimentais, tais como tipo e concentração do ácido, temperatura e tempo de aquecimento, sistema de solventes e tempo de exposição ao UV se mostraram críticos e por isso foram cuidadosamente estudados. As características do reator também se mostraram importantes para o sucesso do procedimento. A intensidade da fluorescência (excitação em 240 nm e emissão em 350 nm) e a estabilidade dos fotoprodutos se mostraram apropriados para permitir o desenvolvimento de um método espectrofluorimétrico. Parâmetros instrumentais importantes, tais como banda espectral de passagem e a velocidade de varredura foram otimizados, visando à obtenção da melhor razão sinal do analito/sinal do branco e da melhor resolução espectral. Parâmetros analíticos de mérito, obtidos a partir das curvas analíticas, revelaram limites de detecção de 5 e 6 ng mL-1 para triancinolona acetonido e prednisolona, respectivamente; e limites de quantificação de 17 ng mL-1 para a triancinolona acetonido e 19 ng mL-1 para a prednisolona. As faixas lineares dinâmicas, nos dois casos, se estenderam por três ordens de grandeza com coeficientes de linearidade (r2) de 0,99. Este método espectrofluorimétrico foi testado em formulações farmacêuticas, obtendo-se os melhores resultados para os comprimidos e soluções injetáveis. Estudos para avaliar o efeito de dois potenciais interferentes (polimixina B e benzocaína) também foram realizados. Resultados de recuperação foram avaliados tomando como referência os valores indicados na bula do medicamento e também valores obtidos com o procedimento de referência (HPLC com detecção fotométrica UVvis) utilizado no Jockey Club Brasileiro, obtendo resultados entre 97 ± 14 e 104 ± 6 %. / [en] The synthetic glucocorticoid such as triamcinolone acetonide and prednisolone neither present natural fluorescence nor fluorescence can be induced by means of the standard procedure used for natural glucocorticoids which consists on a treatment with concentrated sulfuric acid. In the present work, a photochemical derivatization procedure for these two synthetic glucocorticoids was developed and carefully optimized aiming the obtantion of fluorescent derivatives stable enough to allow the development of a spectrofluorimetric method for determination of these analytes in pharmaceutical formulations. The photochemical derivatization procedure consisted on the exposure of acidic solutions of these synthetic glucocorticoids to the ultraviolet radiation (300 nm) in a photochemical reactor. Experimental parameters such as type and concentration of the acid, temperature and heating time, solvent system and UV exposition time have shown to be critical and therefore they were carefully studied. The design of the photochemical reactor) has also shown to be relevant for the success of the procedure. The intensity of the fluorescence (with maximum excitation and emission wavelenghts at 240 nm and 350 nm respectively) and the stability of these photoproducts, have shown to be appropriated for the development of a spectrofluorimetric method. Important instrumental parameters such as spectral bandpass and scan velocity have been optimized aiming the achievement of best signal-to-blank ratio and spectral resolution. Analytical parameters of merit, obtained from the analytical curve, have indicated limits of detention of 5 and 6 ng mL-1 for triamcinolone acetonide and prednisolone, respectively, and limits of quantification of 17 ng mL-1 for triamcinolone acetonide and 18 ng mL-1 for prednisolone. The linear dynamic range for both analytes extended over three orders of magnitude with linear coefficients (r2) of 0,99. The spectrofluorimetric method was tested by the analysis of pharmaceutical formulations, with best performance for tablets and injectable solutions. A study to evaluate the effect of two potential interferents (polimixine B and benzocaine) has also been made. Recovery results were evaluated using both, the reference values indicated in the medicine instructions and concentration values obtained using the reference procedure (HPLC with UV-visible photometric detection) used in the Brazilian Jockey Club. Satisfactory recovery results were achieved (between 97 ± 14 and 104 ± 6 %).

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