Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design

Detalhes bibliográficos
Autor(a) principal: Anacleto, Beatriz Casimiro Soares
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/25630
Resumo: The presence of residual solvents in pharmaceuticals represents one of the main concerns of the pharmaceutical industry due to its impact on both products’ properties and patients’ health. For these reasons, it is necessary to develop analytical strategies that support the decision making process in each stage of the pharmaceutical development and simultaneously maximize the efficiency and productivity of the laboratory responsible for pharmaceutical quality control. In this thesis, a general Static Headspace-Gas Chromatography method was developed applying the Analytical Quality by Design (AQbD) approach for determination of residual solvents in Hovione FarmaCiencia SA. The column flow, oven temperature program, split ratio, split at vent, vial pressure and headspace equilibration temperature and time were identified as critical method parameters. In order to optimize the selectivity, sensibility and run time, these parameters were studied through experimental design plans and statistical analysis. From the obtained design space, the final operating conditions of the method were selected. The robustness of the method was verified and confirmed. The validation results demonstrated specificity, selectivity, sensitivity, linearity, accuracy and precision, so the developed method is suitable for the determination of 29 different residual solvents in pharmaceutical samples. The application of the AQbD approach allowed to acquire the maximum understanding about the method and to minimize the impact of the sources of variability in its performance.
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spelling Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by DesignResidual solventsPharmaceutical samplesStatic Headspace Gas ChromatographyAnalytical Quality by DesignAnalytical developmentThe presence of residual solvents in pharmaceuticals represents one of the main concerns of the pharmaceutical industry due to its impact on both products’ properties and patients’ health. For these reasons, it is necessary to develop analytical strategies that support the decision making process in each stage of the pharmaceutical development and simultaneously maximize the efficiency and productivity of the laboratory responsible for pharmaceutical quality control. In this thesis, a general Static Headspace-Gas Chromatography method was developed applying the Analytical Quality by Design (AQbD) approach for determination of residual solvents in Hovione FarmaCiencia SA. The column flow, oven temperature program, split ratio, split at vent, vial pressure and headspace equilibration temperature and time were identified as critical method parameters. In order to optimize the selectivity, sensibility and run time, these parameters were studied through experimental design plans and statistical analysis. From the obtained design space, the final operating conditions of the method were selected. The robustness of the method was verified and confirmed. The validation results demonstrated specificity, selectivity, sensitivity, linearity, accuracy and precision, so the developed method is suitable for the determination of 29 different residual solvents in pharmaceutical samples. The application of the AQbD approach allowed to acquire the maximum understanding about the method and to minimize the impact of the sources of variability in its performance.A presença de solventes residuais em produtos farmacêuticos representa uma das principais preocupações da indústria farmacêutica, devido ao seu impacto nas propriedades dos produtos e na saúde dos pacientes. Por estes motivos, torna-se necessário desenvolver estratégias analíticas que suportem decisões em cada fase do desenvolvimento farmacêutico e simultaneamente maximizem a eficiência e produtividade do laboratório de controlo de qualidade farmacêutico. Nesta tese foi desenvolvido um método geral de Cromatografia Gasosa com amostragem por Headspace estático aplicando a abordagem Qualidade Analítica por Design (AQbD), para a determinação de solventes residuais na Hovione FarmaCiencia SA. O fluxo da coluna, o programa de temperatura do forno, o split ratio, o split at vent, a pressão do vial e a temperatura e o tempo de equilíbrio do headspace foram identificados como parâmetros críticos do método. De forma a otimizar a seletividade, a sensibilidade e o tempo de análise, estes parâmetros foram estudados através de planos de desenho experimental e de análises estatísticas. A partir do espaço de design obtido, foram selecionadas as condições operatórias finais do método. A robustez do método foi verificada e confirmada. Os resultados de validação demonstraram especificidade, seletividade, sensibilidade, linearidade, exatidão e precisão, pelo que o método desenvolvido é adequado à determinação de 29 solventes residuais diferentes em amostras farmacêuticas. A aplicação da abordagem AQbD permitiu adquirir o máximo conhecimento acerca do método e minimizar o impacto das fontes de variabilidade na sua performance.2021-01-04T00:00:00Z2018-12-19T00:00:00Z2018-12-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/25630TID:202238792engAnacleto, Beatriz Casimiro Soaresinfo: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:RCAAP2024-02-22T11:49:41Zoai:ria.ua.pt:10773/25630Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:58:49.238557Repositório 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 Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
title Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
spellingShingle Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
Anacleto, Beatriz Casimiro Soares
Residual solvents
Pharmaceutical samples
Static Headspace Gas Chromatography
Analytical Quality by Design
Analytical development
title_short Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
title_full Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
title_fullStr Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
title_full_unstemmed Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
title_sort Determination of residual solvents in pharmaceuticals: development of a general analytical method applying Quality by Design
author Anacleto, Beatriz Casimiro Soares
author_facet Anacleto, Beatriz Casimiro Soares
author_role author
dc.contributor.author.fl_str_mv Anacleto, Beatriz Casimiro Soares
dc.subject.por.fl_str_mv Residual solvents
Pharmaceutical samples
Static Headspace Gas Chromatography
Analytical Quality by Design
Analytical development
topic Residual solvents
Pharmaceutical samples
Static Headspace Gas Chromatography
Analytical Quality by Design
Analytical development
description The presence of residual solvents in pharmaceuticals represents one of the main concerns of the pharmaceutical industry due to its impact on both products’ properties and patients’ health. For these reasons, it is necessary to develop analytical strategies that support the decision making process in each stage of the pharmaceutical development and simultaneously maximize the efficiency and productivity of the laboratory responsible for pharmaceutical quality control. In this thesis, a general Static Headspace-Gas Chromatography method was developed applying the Analytical Quality by Design (AQbD) approach for determination of residual solvents in Hovione FarmaCiencia SA. The column flow, oven temperature program, split ratio, split at vent, vial pressure and headspace equilibration temperature and time were identified as critical method parameters. In order to optimize the selectivity, sensibility and run time, these parameters were studied through experimental design plans and statistical analysis. From the obtained design space, the final operating conditions of the method were selected. The robustness of the method was verified and confirmed. The validation results demonstrated specificity, selectivity, sensitivity, linearity, accuracy and precision, so the developed method is suitable for the determination of 29 different residual solvents in pharmaceutical samples. The application of the AQbD approach allowed to acquire the maximum understanding about the method and to minimize the impact of the sources of variability in its performance.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-19T00:00:00Z
2018-12-19
2021-01-04T00:00:00Z
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/10773/25630
TID:202238792
url http://hdl.handle.net/10773/25630
identifier_str_mv TID:202238792
dc.language.iso.fl_str_mv eng
language eng
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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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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