Evaluation and Prediction of the physical stability of amorphous drugs
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/89611 |
Resumo: | The formulation of amorphous solids dispersion (ASDs) is a vanguard strategy used for the improvement of aqueous solubility and bioavailability of poorly water-soluble drugs. During formulation development it is very important to evaluate and predict long term physical stability of ASDs, particularly in supersaturated systems, since these forms are thermodynamically unstable. This project focuses not only on the evaluation of different thermodynamic and kinetics parameters that govern physical stability, but also on the development of a model that can effectively predict long term stability. Six amorphous drugs and three amorphous solid dispersions were studied and parameters such as glass transition, fragility, relaxation and Kauzmann temperature were evaluated. A stability study was also conducted at 30 ºC to investigate potential correlations between the parameters and the onset of crystallization, which was monitored by X-ray Powder Diffraction (XRPD). Differential Scanning Calorimetry (DSC) and Dielectric Spectroscopy (DRS) were also used to determine all parameters abovementioned. The study revealed that glass transition is not indicative of the physical stability of ASDs and, simultaneously, that the fragility index is not enough to rank the physical stability of amorphous drugs. Furthermore, a predictive model, that combines thermodynamic parameters with the kinetics of relaxation, was developed and showed to be a good indicator of physical stability. This approach was successfully employed allowing not only an early-stage assessment of physical stability, during the pre-formulation stage, but also an advanced analytical characterization. |
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Evaluation and Prediction of the physical stability of amorphous drugsAmorphous solid dispersionphysical stabilityKauzmann temperaturerelaxationcrystallizationglass transition temperatureDomínio/Área Científica::Engenharia e Tecnologia::Engenharia QuímicaThe formulation of amorphous solids dispersion (ASDs) is a vanguard strategy used for the improvement of aqueous solubility and bioavailability of poorly water-soluble drugs. During formulation development it is very important to evaluate and predict long term physical stability of ASDs, particularly in supersaturated systems, since these forms are thermodynamically unstable. This project focuses not only on the evaluation of different thermodynamic and kinetics parameters that govern physical stability, but also on the development of a model that can effectively predict long term stability. Six amorphous drugs and three amorphous solid dispersions were studied and parameters such as glass transition, fragility, relaxation and Kauzmann temperature were evaluated. A stability study was also conducted at 30 ºC to investigate potential correlations between the parameters and the onset of crystallization, which was monitored by X-ray Powder Diffraction (XRPD). Differential Scanning Calorimetry (DSC) and Dielectric Spectroscopy (DRS) were also used to determine all parameters abovementioned. The study revealed that glass transition is not indicative of the physical stability of ASDs and, simultaneously, that the fragility index is not enough to rank the physical stability of amorphous drugs. Furthermore, a predictive model, that combines thermodynamic parameters with the kinetics of relaxation, was developed and showed to be a good indicator of physical stability. This approach was successfully employed allowing not only an early-stage assessment of physical stability, during the pre-formulation stage, but also an advanced analytical characterization.Sousa, LuísRUNVeiga, Cíntia Leonora Semedo2022-10-01T00:30:47Z2019-11-0720192019-11-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/89611enginfo: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:RCAAP2024-03-11T04:39:55Zoai:run.unl.pt:10362/89611Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:37:02.415675Repositório 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 |
Evaluation and Prediction of the physical stability of amorphous drugs |
title |
Evaluation and Prediction of the physical stability of amorphous drugs |
spellingShingle |
Evaluation and Prediction of the physical stability of amorphous drugs Veiga, Cíntia Leonora Semedo Amorphous solid dispersion physical stability Kauzmann temperature relaxation crystallization glass transition temperature Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química |
title_short |
Evaluation and Prediction of the physical stability of amorphous drugs |
title_full |
Evaluation and Prediction of the physical stability of amorphous drugs |
title_fullStr |
Evaluation and Prediction of the physical stability of amorphous drugs |
title_full_unstemmed |
Evaluation and Prediction of the physical stability of amorphous drugs |
title_sort |
Evaluation and Prediction of the physical stability of amorphous drugs |
author |
Veiga, Cíntia Leonora Semedo |
author_facet |
Veiga, Cíntia Leonora Semedo |
author_role |
author |
dc.contributor.none.fl_str_mv |
Sousa, Luís RUN |
dc.contributor.author.fl_str_mv |
Veiga, Cíntia Leonora Semedo |
dc.subject.por.fl_str_mv |
Amorphous solid dispersion physical stability Kauzmann temperature relaxation crystallization glass transition temperature Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química |
topic |
Amorphous solid dispersion physical stability Kauzmann temperature relaxation crystallization glass transition temperature Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química |
description |
The formulation of amorphous solids dispersion (ASDs) is a vanguard strategy used for the improvement of aqueous solubility and bioavailability of poorly water-soluble drugs. During formulation development it is very important to evaluate and predict long term physical stability of ASDs, particularly in supersaturated systems, since these forms are thermodynamically unstable. This project focuses not only on the evaluation of different thermodynamic and kinetics parameters that govern physical stability, but also on the development of a model that can effectively predict long term stability. Six amorphous drugs and three amorphous solid dispersions were studied and parameters such as glass transition, fragility, relaxation and Kauzmann temperature were evaluated. A stability study was also conducted at 30 ºC to investigate potential correlations between the parameters and the onset of crystallization, which was monitored by X-ray Powder Diffraction (XRPD). Differential Scanning Calorimetry (DSC) and Dielectric Spectroscopy (DRS) were also used to determine all parameters abovementioned. The study revealed that glass transition is not indicative of the physical stability of ASDs and, simultaneously, that the fragility index is not enough to rank the physical stability of amorphous drugs. Furthermore, a predictive model, that combines thermodynamic parameters with the kinetics of relaxation, was developed and showed to be a good indicator of physical stability. This approach was successfully employed allowing not only an early-stage assessment of physical stability, during the pre-formulation stage, but also an advanced analytical characterization. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-11-07 2019 2019-11-07T00:00:00Z 2022-10-01T00:30:47Z |
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 |
http://hdl.handle.net/10362/89611 |
url |
http://hdl.handle.net/10362/89611 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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.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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1799137987603202048 |