Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Pharmaceutical Sciences |
Texto Completo: | https://www.revistas.usp.br/bjps/article/view/128381 |
Resumo: | Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs. |
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Brazilian Journal of Pharmaceutical Sciences |
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Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental designFormulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2016-12-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/12838110.1590/s1984-82502016000400009Brazilian Journal of Pharmaceutical Sciences; Vol. 52 Núm. 4 (2016); 653-667Brazilian Journal of Pharmaceutical Sciences; v. 52 n. 4 (2016); 653-667Brazilian Journal of Pharmaceutical Sciences; Vol. 52 No. 4 (2016); 653-6672175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/128381/125254Copyright (c) 2018 Brazilian Journal of Pharmaceutical Sciences (Impresso)info:eu-repo/semantics/openAccessShahba, Ahmad Abdul-WahhabMohsin, KaziAlanazi, Fars KaedAbdel-Rahman, Sayed Ibrahim2017-03-16T18:09:44Zoai:revistas.usp.br:article/128381Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2017-03-16T18:09:44Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
title |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
spellingShingle |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design Shahba, Ahmad Abdul-Wahhab |
title_short |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
title_full |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
title_fullStr |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
title_full_unstemmed |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
title_sort |
Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design |
author |
Shahba, Ahmad Abdul-Wahhab |
author_facet |
Shahba, Ahmad Abdul-Wahhab Mohsin, Kazi Alanazi, Fars Kaed Abdel-Rahman, Sayed Ibrahim |
author_role |
author |
author2 |
Mohsin, Kazi Alanazi, Fars Kaed Abdel-Rahman, Sayed Ibrahim |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Shahba, Ahmad Abdul-Wahhab Mohsin, Kazi Alanazi, Fars Kaed Abdel-Rahman, Sayed Ibrahim |
description |
Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/128381 10.1590/s1984-82502016000400009 |
url |
https://www.revistas.usp.br/bjps/article/view/128381 |
identifier_str_mv |
10.1590/s1984-82502016000400009 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/128381/125254 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2018 Brazilian Journal of Pharmaceutical Sciences (Impresso) info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2018 Brazilian Journal of Pharmaceutical Sciences (Impresso) |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
dc.source.none.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences; Vol. 52 Núm. 4 (2016); 653-667 Brazilian Journal of Pharmaceutical Sciences; v. 52 n. 4 (2016); 653-667 Brazilian Journal of Pharmaceutical Sciences; Vol. 52 No. 4 (2016); 653-667 2175-9790 1984-8250 reponame:Brazilian Journal of Pharmaceutical Sciences instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Brazilian Journal of Pharmaceutical Sciences |
collection |
Brazilian Journal of Pharmaceutical Sciences |
repository.name.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
bjps@usp.br||elizabeth.igne@gmail.com |
_version_ |
1800222912864583680 |