Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/001300000sw28 |
Texto Completo: | http://repositorio.ufsm.br/handle/1/5982 |
Resumo: | This work aimed the development of polymeric microparticles containing sodium risedronate from Eudragit S100® (MP-EUD) and the blend, Eudragit S100® and Pullulan (MP-EUD-PUL), through spray-drying technique. MP-EUD were obtained with a yield of 54%, encapsulation efficiency of 90%, average particle size of 3.3 μm and presented spherical shape. The moisture content was 8% and the Carr Index and Hausner Factor indicated poor flowability. At pH 1.2 23% risedronate sodium was released after 120 min, while the drug at pH 6.8 took 90 min to reach 99.5%. The mathematical modeling showed that the drug release followed first order kinetics and Fickian diffusion. Tablets prepared by direct compression of MP-EUD using different polyvinylpirrolidone concentrations showed low weight variation, thickness and drug content. Furthermore, they presented low friability and adequate hardness. In vitro studies indicated that no more than 16% of the drug was released in 120 min at pH 1.2. At pH 6.8 the risedronate release was prolonged for 270 min and folowed first order kinetics and Fickian diffusion. Concerning MP-EUD-PUL, three proportions of Eudragit S100® and Pullulan (1:2, 1:1 and 2:1) were studied. Microparticles were obtained with yields ranging from 31% to 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, mean particle size in the range of 2.9 μm - 4.8 μm and narrow size distributions. Carr index and Hausner ratio indicated poor flowability. In gastric simulated fluid the microparticles prepared with the highest amount of Eudragit S100® showed the best gastroresistance. In intestinal simulated fluid blend microparticles were able to prolong the drug release. MP-EUD-PUL 2:1 were compressed into tablets with or without a binder. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for untableted microparticles and were also able to prolong risedronate release. Finally, the formulations developed in this study represent promising alternatives for sodium risedronate oral delivery. |
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Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódioDevelopment of microparticulate systems intended for oral release of sodium risedronateRisedronato de sódioBisfosfonatosMicropartículasComprimidosLiberação oralSodium risedronateBisphosphonatesMicroparticlesTabletsOral releaseCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAThis work aimed the development of polymeric microparticles containing sodium risedronate from Eudragit S100® (MP-EUD) and the blend, Eudragit S100® and Pullulan (MP-EUD-PUL), through spray-drying technique. MP-EUD were obtained with a yield of 54%, encapsulation efficiency of 90%, average particle size of 3.3 μm and presented spherical shape. The moisture content was 8% and the Carr Index and Hausner Factor indicated poor flowability. At pH 1.2 23% risedronate sodium was released after 120 min, while the drug at pH 6.8 took 90 min to reach 99.5%. The mathematical modeling showed that the drug release followed first order kinetics and Fickian diffusion. Tablets prepared by direct compression of MP-EUD using different polyvinylpirrolidone concentrations showed low weight variation, thickness and drug content. Furthermore, they presented low friability and adequate hardness. In vitro studies indicated that no more than 16% of the drug was released in 120 min at pH 1.2. At pH 6.8 the risedronate release was prolonged for 270 min and folowed first order kinetics and Fickian diffusion. Concerning MP-EUD-PUL, three proportions of Eudragit S100® and Pullulan (1:2, 1:1 and 2:1) were studied. Microparticles were obtained with yields ranging from 31% to 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, mean particle size in the range of 2.9 μm - 4.8 μm and narrow size distributions. Carr index and Hausner ratio indicated poor flowability. In gastric simulated fluid the microparticles prepared with the highest amount of Eudragit S100® showed the best gastroresistance. In intestinal simulated fluid blend microparticles were able to prolong the drug release. MP-EUD-PUL 2:1 were compressed into tablets with or without a binder. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for untableted microparticles and were also able to prolong risedronate release. Finally, the formulations developed in this study represent promising alternatives for sodium risedronate oral delivery.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEste trabalho objetivou o desenvolvimento de micropartículas poliméricas contendo risedronato de sódio a partir de Eudragit S100® (MP-EUD) e da blenda, Eudragit S100® e Pullulan (MP-EUD-PUL), através da técnica de secagem por aspersão. As MP-EUD foram obtidas com um rendimento de 54%, eficiência de encapsulamento de 90%, tamanho médio de partícula de 3,3 μm e apresentaram formato esférico. O teor de umidade foi de 8%, o Índice de Carr e o Fator de Hausner indicaram baixa fluidez. Em pH 1,2, 23% do risedronato de sódio foi liberado em 120 min, enquanto que em pH 6,8 o fármaco levou 90 min para ser liberado. A modelagem matemática mostrou que a liberação do fármaco seguiu cinética de primeira ordem e se deu por difusão Fickiana. Comprimidos preparados pela compressão direta das MP-EUD a partir de diferentes concentrações de polivinilpirrolidona apresentaram baixas variações de peso médio, espessura e teor de fármaco. Além disso, apresentaram baixa friabilidade e dureza adequada. Os estudos in vitro mostraram que não mais que 16% do fármaco foi liberado durante 120 min em pH 1,2 enquanto que em pH 6,8 a liberação do fármaco foi prolongada por 270 min, seguindo cinética de primeira ordem e difusão Fickiana. Com relação às MP-EUD-PUL, três proporções de Eudragit S100® e Pullulan (1:2, 1:1 e 2:1) foram estudadas. As micropartículas foram obtidas com rendimento variando entre 31% e 42%, com eficiência de encapsulamento próxima de 100% e umidade abaixo de 11%. O tamanho médio de partícula variou entre 2,9 μm e 4,8 μm com estreita distribuição de tamanho. O Índice de Carr e o Fator de Hausner indicaram baixa fluidez. Em meio gástrico simulado, as micropartículas com maior proporção de Eudragit S100® apresentaram melhor perfil de gastrorresistência, enquanto que em meio intestinal simulado todas foram capazes de prolongar a liberação do fármaco. As MP-EUD-PUL 2:1 sofreram compressão direta na ausência ou na presença de polivilpirrolidona. Os comprimidos microparticulados apresentaram pesos médios aceitáveis, teor de fármaco próximo a 100%, dureza e friabilidade dentro do especificado. Os estudos in vitro mostraram que a gastrorresistência foi mantida e que os comprimidos microparticulados também foram capazes de prolongar a liberação do risedronato. Finalmente, as formulações desenvolvidas neste estudo representam alternativas promissoras para a administração oral do risedronato de sódio.Universidade Federal de Santa MariaBRFarmacologiaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCruz, Letíciahttp://lattes.cnpq.br/3095970241017527Alves, Marta Palmahttp://lattes.cnpq.br/0896057648821138Schaffazick, Scheila Rezendehttp://lattes.cnpq.br/3671495623581433Velasquez, Aline de Arce2015-02-132015-02-132012-08-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfVELASQUEZ, Aline de Arce. DEVELOPMENT OF MICROPARTICULATE SYSTEMS INTENDED FOR ORAL RELEASE OF SODIUM RISEDRONATE. 2012. 97 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/5982ark:/26339/001300000sw28porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-02-01T12:28:32Zoai:repositorio.ufsm.br:1/5982Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-02-01T12:28:32Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio Development of microparticulate systems intended for oral release of sodium risedronate |
title |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio |
spellingShingle |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio Velasquez, Aline de Arce Risedronato de sódio Bisfosfonatos Micropartículas Comprimidos Liberação oral Sodium risedronate Bisphosphonates Microparticles Tablets Oral release CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio |
title_full |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio |
title_fullStr |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio |
title_full_unstemmed |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio |
title_sort |
Desenvolvimento de sistemas microparticulados planejados para a liberação oral do risedronato de sódio |
author |
Velasquez, Aline de Arce |
author_facet |
Velasquez, Aline de Arce |
author_role |
author |
dc.contributor.none.fl_str_mv |
Cruz, Letícia http://lattes.cnpq.br/3095970241017527 Alves, Marta Palma http://lattes.cnpq.br/0896057648821138 Schaffazick, Scheila Rezende http://lattes.cnpq.br/3671495623581433 |
dc.contributor.author.fl_str_mv |
Velasquez, Aline de Arce |
dc.subject.por.fl_str_mv |
Risedronato de sódio Bisfosfonatos Micropartículas Comprimidos Liberação oral Sodium risedronate Bisphosphonates Microparticles Tablets Oral release CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Risedronato de sódio Bisfosfonatos Micropartículas Comprimidos Liberação oral Sodium risedronate Bisphosphonates Microparticles Tablets Oral release CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
This work aimed the development of polymeric microparticles containing sodium risedronate from Eudragit S100® (MP-EUD) and the blend, Eudragit S100® and Pullulan (MP-EUD-PUL), through spray-drying technique. MP-EUD were obtained with a yield of 54%, encapsulation efficiency of 90%, average particle size of 3.3 μm and presented spherical shape. The moisture content was 8% and the Carr Index and Hausner Factor indicated poor flowability. At pH 1.2 23% risedronate sodium was released after 120 min, while the drug at pH 6.8 took 90 min to reach 99.5%. The mathematical modeling showed that the drug release followed first order kinetics and Fickian diffusion. Tablets prepared by direct compression of MP-EUD using different polyvinylpirrolidone concentrations showed low weight variation, thickness and drug content. Furthermore, they presented low friability and adequate hardness. In vitro studies indicated that no more than 16% of the drug was released in 120 min at pH 1.2. At pH 6.8 the risedronate release was prolonged for 270 min and folowed first order kinetics and Fickian diffusion. Concerning MP-EUD-PUL, three proportions of Eudragit S100® and Pullulan (1:2, 1:1 and 2:1) were studied. Microparticles were obtained with yields ranging from 31% to 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, mean particle size in the range of 2.9 μm - 4.8 μm and narrow size distributions. Carr index and Hausner ratio indicated poor flowability. In gastric simulated fluid the microparticles prepared with the highest amount of Eudragit S100® showed the best gastroresistance. In intestinal simulated fluid blend microparticles were able to prolong the drug release. MP-EUD-PUL 2:1 were compressed into tablets with or without a binder. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for untableted microparticles and were also able to prolong risedronate release. Finally, the formulations developed in this study represent promising alternatives for sodium risedronate oral delivery. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-08-27 2015-02-13 2015-02-13 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
VELASQUEZ, Aline de Arce. DEVELOPMENT OF MICROPARTICULATE SYSTEMS INTENDED FOR ORAL RELEASE OF SODIUM RISEDRONATE. 2012. 97 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/5982 |
dc.identifier.dark.fl_str_mv |
ark:/26339/001300000sw28 |
identifier_str_mv |
VELASQUEZ, Aline de Arce. DEVELOPMENT OF MICROPARTICULATE SYSTEMS INTENDED FOR ORAL RELEASE OF SODIUM RISEDRONATE. 2012. 97 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2012. ark:/26339/001300000sw28 |
url |
http://repositorio.ufsm.br/handle/1/5982 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1815172395441324032 |