Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica
Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are th...
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rifampicina isoniazida sistemas multiparticulados revestimento entérico rifampicin isoniazid multiparticulate systems enteric coating CNPQ::CIENCIAS DA SAUDE::FARMACIA |
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rifampicina isoniazida sistemas multiparticulados revestimento entérico rifampicin isoniazid multiparticulate systems enteric coating CNPQ::CIENCIAS DA SAUDE::FARMACIA Freire, Fátima Duarte Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
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Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage |
| author2 |
Raffin, Fernanda Nervo |
| author_facet |
Raffin, Fernanda Nervo Freire, Fátima Duarte |
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masterThesis |
| author |
Freire, Fátima Duarte |
| author_sort |
Freire, Fátima Duarte |
| title |
Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
| title_short |
Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
| title_full |
Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
| title_fullStr |
Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
| title_full_unstemmed |
Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
| title_sort |
obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica |
| publisher |
Universidade Federal do Rio Grande do Norte |
| publishDate |
2014 |
| url |
https://repositorio.ufrn.br/jspui/handle/123456789/13447 |
| work_keys_str_mv |
AT freirefatimaduarte obtencaodesistemasmultiparticuladosdeisoniazidarevestidoscompolimerodeliberacaoenterica |
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1773961951784730624 |
| spelling |
ri-123456789-134472019-05-26T05:33:35Z Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica Freire, Fátima Duarte Raffin, Fernanda Nervo http://lattes.cnpq.br/6731205787443155 http://lattes.cnpq.br/1052562183676637 Egito, Eryvaldo Sócrates Tabosa do http://lattes.cnpq.br/6907806915889763 Chaud, Marco Vinícius http://lattes.cnpq.br/8853705702222360 rifampicina isoniazida sistemas multiparticulados revestimento entérico rifampicin isoniazid multiparticulate systems enteric coating CNPQ::CIENCIAS DA SAUDE::FARMACIA Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage Conhecida há milhares de anos, a tuberculose (TB) é a principal causa de mortalidade por uma única doença infecciosa devido à falta de adesão dos pacientes aos esquemas terapêuticos disponíveis, o aparecimento de cepas multiresistentes e a co-infecção com o vírus HIV. A isoniazida e a rifampicina possuem o maior poder bactericida frente ao M. tuberculosis, sendo por isso unanimidade no tratamento anti-TB em todo o mundo. No entanto, a rifampicina em condições ácidas do estômago degrada-se rapidamente, principalmente na presença da isoniazida, diminuindo a quantidade de fármaco disponível para absorção bem como a sua biodisponibilidade, contribuindo para a resistência crescente aos fármacos tuberculostáticos. A rifampicina é bem absorvida no estômago devido à sua alta solubilidade entre pH 1 e 2 e a absorção gástrica da isoniazida é considerada pobre, sendo então, majoritariamente intestinal. O presente trabalho teve como objetivo o desenvolvimento de sistemas multiparticulados (granulados e péletes) de isoniazida gastrorresistentes visando evitar contato da rifampicina com isoniazida e conseqüente degradação no meio ácido estomacal bem como modular a liberação da isoniazida no intestino. Granulados de isoniazida foram obtidos por via úmida utilizando solução alcoólica e solução aquosa de PVP K-30 como agente agregante/aglutinante, nas proporções 5, 8 e 10%. A influência do excipiente (amido, celulose ou ausência de diluente) sobre as propriedades físicas e tecnológicas dos granulados foi investigada. Os péletes foram produzidos pela técnica de extrusão-esferonização utilizando isoniazida e Celulose MC 101 (na proporção 85:15) e solução aquosa de Methocel 1% como agregante. Os péletes apresentaram vantagens em relação aos granulados, como: maior densidade aparente, menor diferença entre as densidades aparente e de compactação, superfície mais lisa e, principalmente, menor friabilidade, sendo então revestidos com uma solução orgânica de Acrycoat L 100® em leito fluidizado. Diferentes percentuais de revestimento (15, 25 e 50%) foram aplicados aos péletes, os quais tiveram seus comportamentos avaliados in vitro por dissolução em meio ácido e básico. Em seguida, a dissolução da rifampicina em meio ácido na presença da isoniazida em péletes não revestidos e péletes revestidos foi avaliada também. Os resultados indicam que a gastrorresistência foi obtida somente com a maior quantidade de revestimento, sendo a isoniazida liberada com sucesso na etapa básica. A quantidade de rifampicina dissolvida quando associada a péletes de isoniazida não revestidos foi menor do que a observada na presença de péletes de liberação entérica. O polímero Acrycoat L 100® mostrou-se eficiente para o recobrimento com a função de gastrorresistência, podendo resolver o problema da baixa biodisponibilidade da rifampicina assim como ajudar a diminuir a dosagem utilizada 2014-12-17T14:16:24Z 2010-03-17 2014-12-17T14:16:24Z 2009-09-21 masterThesis FREIRE, Fátima Duarte. Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica. 2009. 98 f. Dissertação (Mestrado em Bioanálises e Medicamentos) - Universidade Federal do Rio Grande do Norte, Natal, 2009. https://repositorio.ufrn.br/jspui/handle/123456789/13447 por Acesso Embargado application/pdf application/pdf application/pdf Universidade Federal do Rio Grande do Norte BR UFRN Programa de Pós-Graduação em Ciências Farmacêuticas Bioanálises e Medicamentos |