Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona

Detalhes bibliográficos
Autor(a) principal: Brendle, Martina Gehrke
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/6022
Resumo: Idebenone is an antioxidant, a synthetic derivative of coenzyme Q10, with several applications, such as neuroprotection. However, this drug has low solubility in water, besides is irritant substance and has chemical instability. Hence, idebenone-loaded nano-organized systems have been developed, such as polymeric nanocapsules (NC). Vegetable oils containing antioxidants such as coconut oil and palm oil can be interesting for the composition of these particles. In this way, the aim of this work was to develop NC suspensions containing different oils as core (palm, coconut or medium chain triglycerides) for delivery of neuroprotective agent idebenone in order to compare the behavior of these systems concerning physico-chemical stability, photostability, controlled release, and conversion to redispersible solid dosage forms (lyophilized products). The nanocapsules were prepared by interfacial deposition of preformed polymer. As the results, it was possible to prepare poly(Ɛ-caprolactone) NC suspensions and palm oil (PO/PCL) or Eudragit® RS100 and coconut oil (OC/EUD) containing idebenone (1.0 mg/mL) with appropriate physico-chemical characteristics. Parameters such as the proportion of aqueous phase/organic phase, type of both surfactant (low HLB) and polymer influenced the optimization of these systems. For comparison, corresponding formulations were prepared with medium chain triglycerides (TCM/PCL or TCM/EUD), using the same conditions. The suspensions had an average diameter between 166 and 216nm, low polydispersity index (0.085 to 0.142), positive or negative zeta potential, depending on the characteristics of the polymer, and high encapsulation efficiency. The maintenance of average particle diameter and low polydispersity index have be verified during stability study (room temperature and exposed or not to light) for 75 days. However, the idebenone content significantly decreased in this period, with influence on the type of polymer. Thereafter, photostability study has shown that the suspensions NC OP/PCL (UVC/UVA) and TCM/PCL (UVA) were able to significantly reduce the degradation of idebenone (content: 53,7-76,1%) compared to an aqueous micellar (content: 31,2-63,1%) dispersion containing the drug. In addition, these systems were able to promoting drug controlled release (t1/2 26 h), without burst effect, showing monoexponential profile (t1/2< 3.0 h for free drug). The lyophilization of suspensions, employing trehalose as soluble carbohydrate, resulted in suitable and redispersible products (content of 96-100%, less than 3.6% moisture; 0.8-1.2 index), presenting several spherical structures, including in colloidal range, featuring the presence of NC in these dried products. In the stability study (room temperature/protection from light and moisture), it was observed that the lyophilized products were able to delay or decrease the degradation of idebenone compared to suspensions of origin, regardless of the both type of polymer (PCL/EUD) and oil (OP/OC/TCM). In conclusion, the developed systems are promising for the controlled release of neuroprotective drug idebenone.
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spelling Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenonaTechnological development of polymeric nanocapsules suspensions and freeze-dried powders for release of neuroprotective idebenoneNanocápsulasIdebenonaÓleo de palmaÓleo de cocoTriglicerídeos de cadeia médiaLiofilizaçãoTrealoseEstabilidadeLiberação controladaNanocapsulesIdebenonePalm oilCoconut oilMedium chain triglyceridesFreeze-dryingTrealoseStabitityControlled releaseCNPQ::CIENCIAS DA SAUDE::FARMACIAIdebenone is an antioxidant, a synthetic derivative of coenzyme Q10, with several applications, such as neuroprotection. However, this drug has low solubility in water, besides is irritant substance and has chemical instability. Hence, idebenone-loaded nano-organized systems have been developed, such as polymeric nanocapsules (NC). Vegetable oils containing antioxidants such as coconut oil and palm oil can be interesting for the composition of these particles. In this way, the aim of this work was to develop NC suspensions containing different oils as core (palm, coconut or medium chain triglycerides) for delivery of neuroprotective agent idebenone in order to compare the behavior of these systems concerning physico-chemical stability, photostability, controlled release, and conversion to redispersible solid dosage forms (lyophilized products). The nanocapsules were prepared by interfacial deposition of preformed polymer. As the results, it was possible to prepare poly(Ɛ-caprolactone) NC suspensions and palm oil (PO/PCL) or Eudragit® RS100 and coconut oil (OC/EUD) containing idebenone (1.0 mg/mL) with appropriate physico-chemical characteristics. Parameters such as the proportion of aqueous phase/organic phase, type of both surfactant (low HLB) and polymer influenced the optimization of these systems. For comparison, corresponding formulations were prepared with medium chain triglycerides (TCM/PCL or TCM/EUD), using the same conditions. The suspensions had an average diameter between 166 and 216nm, low polydispersity index (0.085 to 0.142), positive or negative zeta potential, depending on the characteristics of the polymer, and high encapsulation efficiency. The maintenance of average particle diameter and low polydispersity index have be verified during stability study (room temperature and exposed or not to light) for 75 days. However, the idebenone content significantly decreased in this period, with influence on the type of polymer. Thereafter, photostability study has shown that the suspensions NC OP/PCL (UVC/UVA) and TCM/PCL (UVA) were able to significantly reduce the degradation of idebenone (content: 53,7-76,1%) compared to an aqueous micellar (content: 31,2-63,1%) dispersion containing the drug. In addition, these systems were able to promoting drug controlled release (t1/2 26 h), without burst effect, showing monoexponential profile (t1/2< 3.0 h for free drug). The lyophilization of suspensions, employing trehalose as soluble carbohydrate, resulted in suitable and redispersible products (content of 96-100%, less than 3.6% moisture; 0.8-1.2 index), presenting several spherical structures, including in colloidal range, featuring the presence of NC in these dried products. In the stability study (room temperature/protection from light and moisture), it was observed that the lyophilized products were able to delay or decrease the degradation of idebenone compared to suspensions of origin, regardless of the both type of polymer (PCL/EUD) and oil (OP/OC/TCM). In conclusion, the developed systems are promising for the controlled release of neuroprotective drug idebenone.A idebenona é um antioxidante, derivado sintético da coenzima Q10, com várias aplicações, como em neuroproteção. No entanto, este fármaco possui baixa solubilidade em água, potencial irritativo e instabilidade química, fato que tem despertado o interesse em sua associação a sistemas nano-organizados. Dentre estes, destacam-se as nanocápsulas poliméricas (NC). Óleos vegetais, contendo compostos antioxidantes, como óleo de coco e de palma, podem ser interessantes para a composição destas partículas. Neste sentido, o objetivo deste trabalho foi desenvolver suspensões de NC contendo diferentes óleos como núcleo (palma, coco ou triglicerídeos de cadeia média), almejando à veiculação do neuroprotetor idebenona, de forma a comparar o comportamento dos sistemas quanto à estabilidade físico-química, fotoestabilidade, controle de liberação, além da conversão em formas farmacêuticas sólidas redispersíveis (liofilizados). As NC foram preparadas pelo método de deposição interfacial de polímero pré-formado. Conforme os resultados, foi possível preparar suspensões de NC de poli(ε-caprolactona) e óleo de palma (OP/PCL) ou de Eudragit® RS100 e óleo de coco (OC/EUD), contendo idebenona (1,0 mg/mL), com características físico-químicas adequadas, sendo que fatores como proporção das fases aquosa/orgânica, tipo de tensoativo de baixo EHL e de polímero influenciaram a otimização dos sistemas. Para fins comparativos, formulações correspondentes foram preparadas com triglicerídeos de cadeia média (TCM/PCL ou TCM/EUD), empregando as mesmas condições. As suspensões apresentaram diâmetros médios entre 166 e 216 nm, baixos índices de polidispersão (0,085-0,142), potencial zeta positivo ou negativo, dependendo das características do polímero e elevada eficiência de encapsulamento. Quando estas suspensões foram submetidas a estudo de estabilidade, à temperatura ambiente e expostas ou não à luz, durante 75 dias, verificou-se manutenção dos diâmetros médios de partículas e baixos índices de polidispersão. Entretanto, o teor de idebenona decaiu significativamente neste período, com influência significativa do tipo de polímero. Após, estudo de fotoestabilidade demonstrou que as suspensões de NC OP/PCL (UVC/UVA) e TCM/PCL (UVA) foram capazes de reduzir significativamente a degradação da idebenona (teor remanescente: 53,7-76,1%) em comparação a uma dispersão micelar aquosa contendo o fármaco (teor remanescente: 31,2-63,1%), além de promoverem liberação controlada da mesma (t1/2 26 h), sem efeito burst, com perfil ajustado ao modelo monoexponencial (t1/2<3,0 h para fármaco livre). A liofilização das suspensões, empregando trealose, um carboidrato solúvel, resultou em produtos adequados (teor entre 96-100 %; umidade inferior a 3,6 %), redispersíveis (índice de ressuspensão entre 0,8-1,2) e com a presença de inúmeras estruturas esféricas, inclusive na faixa coloidal, caracterizando a presença das NC nestes produtos secos. No estudo de estabilidade (temperatura ambiente/proteção da luz e da umidade), observou-se que os produtos liofilizados foram capazes de retardar ou diminuir significativamente a degradação da idebenona em comparação às suspensões de origem, independentemente do tipo de polímero (PCL/EUD) e de óleo (OP/OC/TCM). Sendo assim, os sistemas desenvolvidos são promissores para a liberação controlada do neuroprotetor idebenona.Universidade Federal de Santa MariaBRFarmáciaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasSchaffazick, Scheila Rezendehttp://lattes.cnpq.br/3671495623581433Alves, Marta Palmahttp://lattes.cnpq.br/0896057648821138Adams, Andréa Inês Hornhttp://lattes.cnpq.br/6872246935204149Brendle, Martina Gehrke2015-11-122015-11-122013-10-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfBRENDLE, Martina Gehrke. TECHNOLOGICAL DEVELOPMENT OF POLYMERIC NANOCAPSULES SUSPENSIONS AND FREEZE-DRIED POWDERS FOR RELEASE OF NEUROPROTECTIVE IDEBENONE. 2013. 110 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2013.http://repositorio.ufsm.br/handle/1/6022porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-10-11T12:54:58Zoai:repositorio.ufsm.br:1/6022Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-11T12:54:58Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
Technological development of polymeric nanocapsules suspensions and freeze-dried powders for release of neuroprotective idebenone
title Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
spellingShingle Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
Brendle, Martina Gehrke
Nanocápsulas
Idebenona
Óleo de palma
Óleo de coco
Triglicerídeos de cadeia média
Liofilização
Trealose
Estabilidade
Liberação controlada
Nanocapsules
Idebenone
Palm oil
Coconut oil
Medium chain triglycerides
Freeze-drying
Trealose
Stabitity
Controlled release
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
title_full Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
title_fullStr Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
title_full_unstemmed Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
title_sort Desenvolvimento tecnológico de suspensões e liofilizados de nanocápsulas poliméricas para a veiculação do neuroprotetor idebenona
author Brendle, Martina Gehrke
author_facet Brendle, Martina Gehrke
author_role author
dc.contributor.none.fl_str_mv Schaffazick, Scheila Rezende
http://lattes.cnpq.br/3671495623581433
Alves, Marta Palma
http://lattes.cnpq.br/0896057648821138
Adams, Andréa Inês Horn
http://lattes.cnpq.br/6872246935204149
dc.contributor.author.fl_str_mv Brendle, Martina Gehrke
dc.subject.por.fl_str_mv Nanocápsulas
Idebenona
Óleo de palma
Óleo de coco
Triglicerídeos de cadeia média
Liofilização
Trealose
Estabilidade
Liberação controlada
Nanocapsules
Idebenone
Palm oil
Coconut oil
Medium chain triglycerides
Freeze-drying
Trealose
Stabitity
Controlled release
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Nanocápsulas
Idebenona
Óleo de palma
Óleo de coco
Triglicerídeos de cadeia média
Liofilização
Trealose
Estabilidade
Liberação controlada
Nanocapsules
Idebenone
Palm oil
Coconut oil
Medium chain triglycerides
Freeze-drying
Trealose
Stabitity
Controlled release
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Idebenone is an antioxidant, a synthetic derivative of coenzyme Q10, with several applications, such as neuroprotection. However, this drug has low solubility in water, besides is irritant substance and has chemical instability. Hence, idebenone-loaded nano-organized systems have been developed, such as polymeric nanocapsules (NC). Vegetable oils containing antioxidants such as coconut oil and palm oil can be interesting for the composition of these particles. In this way, the aim of this work was to develop NC suspensions containing different oils as core (palm, coconut or medium chain triglycerides) for delivery of neuroprotective agent idebenone in order to compare the behavior of these systems concerning physico-chemical stability, photostability, controlled release, and conversion to redispersible solid dosage forms (lyophilized products). The nanocapsules were prepared by interfacial deposition of preformed polymer. As the results, it was possible to prepare poly(Ɛ-caprolactone) NC suspensions and palm oil (PO/PCL) or Eudragit® RS100 and coconut oil (OC/EUD) containing idebenone (1.0 mg/mL) with appropriate physico-chemical characteristics. Parameters such as the proportion of aqueous phase/organic phase, type of both surfactant (low HLB) and polymer influenced the optimization of these systems. For comparison, corresponding formulations were prepared with medium chain triglycerides (TCM/PCL or TCM/EUD), using the same conditions. The suspensions had an average diameter between 166 and 216nm, low polydispersity index (0.085 to 0.142), positive or negative zeta potential, depending on the characteristics of the polymer, and high encapsulation efficiency. The maintenance of average particle diameter and low polydispersity index have be verified during stability study (room temperature and exposed or not to light) for 75 days. However, the idebenone content significantly decreased in this period, with influence on the type of polymer. Thereafter, photostability study has shown that the suspensions NC OP/PCL (UVC/UVA) and TCM/PCL (UVA) were able to significantly reduce the degradation of idebenone (content: 53,7-76,1%) compared to an aqueous micellar (content: 31,2-63,1%) dispersion containing the drug. In addition, these systems were able to promoting drug controlled release (t1/2 26 h), without burst effect, showing monoexponential profile (t1/2< 3.0 h for free drug). The lyophilization of suspensions, employing trehalose as soluble carbohydrate, resulted in suitable and redispersible products (content of 96-100%, less than 3.6% moisture; 0.8-1.2 index), presenting several spherical structures, including in colloidal range, featuring the presence of NC in these dried products. In the stability study (room temperature/protection from light and moisture), it was observed that the lyophilized products were able to delay or decrease the degradation of idebenone compared to suspensions of origin, regardless of the both type of polymer (PCL/EUD) and oil (OP/OC/TCM). In conclusion, the developed systems are promising for the controlled release of neuroprotective drug idebenone.
publishDate 2013
dc.date.none.fl_str_mv 2013-10-30
2015-11-12
2015-11-12
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 BRENDLE, Martina Gehrke. TECHNOLOGICAL DEVELOPMENT OF POLYMERIC NANOCAPSULES SUSPENSIONS AND FREEZE-DRIED POWDERS FOR RELEASE OF NEUROPROTECTIVE IDEBENONE. 2013. 110 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2013.
http://repositorio.ufsm.br/handle/1/6022
identifier_str_mv BRENDLE, Martina Gehrke. TECHNOLOGICAL DEVELOPMENT OF POLYMERIC NANOCAPSULES SUSPENSIONS AND FREEZE-DRIED POWDERS FOR RELEASE OF NEUROPROTECTIVE IDEBENONE. 2013. 110 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2013.
url http://repositorio.ufsm.br/handle/1/6022
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
Farmácia
UFSM
Programa de Pós-Graduação em Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Farmácia
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
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