Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/68264 |
Resumo: | Amorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen–polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit® L 100 and Eudragit® RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems. |
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Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersionstamoxifensolid dispersionssupersaturationpolymer blendingrecrystallizationScience & TechnologyAmorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen–polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit® L 100 and Eudragit® RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems.This work was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil), by the Portuguese Science and Technology Foundation (FCT/MCT), and European Funds (PRODER/COMPETE) under the projects M-ERA-NET/0004/2015 and UIDB/04469/2020 (strategic fund) and co-financed by FEDER under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersionMultidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoSilva, Dayanne T. C. daNadvorny, DanielaDanda, Lucas J. de A.Vieira, Amanda C. Q. de M.Severino, PatriciaSoares, Monica F. La R.Soares-Sobrinho, José L.Souto, Eliana B.20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/68264engT. C. da Silva, Dayanne; Nadvorny, Daniela; Danda, Lucas J. de A.; Vieira, Amanda C. Q. de M.; Severino, Patricia; Soares, Monica F. La R.; Soares-Sobrinho, José L.; Souto, Eliana, Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions. Crystals, 10(11), 1046, 20202073-43522073-435210.3390/cryst10111046https://www.mdpi.com/journal/crystalsinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:51:23Zoai:repositorium.sdum.uminho.pt:1822/68264Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:50:16.299171Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
title |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
spellingShingle |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions Silva, Dayanne T. C. da tamoxifen solid dispersions supersaturation polymer blending recrystallization Science & Technology |
title_short |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
title_full |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
title_fullStr |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
title_full_unstemmed |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
title_sort |
Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions |
author |
Silva, Dayanne T. C. da |
author_facet |
Silva, Dayanne T. C. da Nadvorny, Daniela Danda, Lucas J. de A. Vieira, Amanda C. Q. de M. Severino, Patricia Soares, Monica F. La R. Soares-Sobrinho, José L. Souto, Eliana B. |
author_role |
author |
author2 |
Nadvorny, Daniela Danda, Lucas J. de A. Vieira, Amanda C. Q. de M. Severino, Patricia Soares, Monica F. La R. Soares-Sobrinho, José L. Souto, Eliana B. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Silva, Dayanne T. C. da Nadvorny, Daniela Danda, Lucas J. de A. Vieira, Amanda C. Q. de M. Severino, Patricia Soares, Monica F. La R. Soares-Sobrinho, José L. Souto, Eliana B. |
dc.subject.por.fl_str_mv |
tamoxifen solid dispersions supersaturation polymer blending recrystallization Science & Technology |
topic |
tamoxifen solid dispersions supersaturation polymer blending recrystallization Science & Technology |
description |
Amorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen–polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit® L 100 and Eudragit® RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/68264 |
url |
http://hdl.handle.net/1822/68264 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
T. C. da Silva, Dayanne; Nadvorny, Daniela; Danda, Lucas J. de A.; Vieira, Amanda C. Q. de M.; Severino, Patricia; Soares, Monica F. La R.; Soares-Sobrinho, José L.; Souto, Eliana, Enhanced dissolution efficiency of tamoxifen combined with methacrylate copolymers in amorphous solid dispersions. Crystals, 10(11), 1046, 2020 2073-4352 2073-4352 10.3390/cryst10111046 https://www.mdpi.com/journal/crystals |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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