Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/111051 |
Resumo: | Currently, about 90% of drugs in development stages present poor-aqueous solubility, belonging to Biopharmaceutics Classification System (BCS) Classes II and IV. A leading technology to improve solubility is the production of amorphous solid dispersions (ASDs). ASDs are typically manufactured by spray drying (SD) and hot melt extrusion (HME), however these techniques are not suitable for “brick-dust” compounds. Coprecipitation is an adequate technology to deal with “brick-dust” compounds, since high boiling point solvents, with higher solubilization power, can be employed. This technology is not without drawbacks: the high volume and low solids’ load of the resultant suspension and the challenging drying of non-volatile organic solvents. With this work, these drawbacks are tackled through a proof-of-concept by incorporating crossflow filtration with hollow fiber membranes after coprecipitation to 1) concentrate the suspension, increasing solids’ load and 2) minimize the presence of the organic solvent, by diafiltration. Coprecipitation was carried out through two different techniques: high shear mixer and high-pressure homogenization (HPH). The suspensions were concentrated and washed in hollow fiber membranes unit and isolated through spray drying. Spray-dried ASDs were also produced to serve as benchmark against the coprecipitated prototypes. Coprecipitated prototypes and SD benchmarks were analytically characterized and the preliminary results seem to indicate a greater dissolution behavior of the HPH prototype. In conclusion, this study demonstrated the advantages of including a cross-filtration with hollow fiber membranes, a straightforward and scalable technology that allows the circumvention of typical pitfalls of the production of “brick-dust” ASDs by coprecipitation. In 60 minutes, the concentration step reduced the mass of HPH suspension to a half, and the diafiltration operations lowered the DSMO initial content in approximately 50% within 112 minutes; although this last step should be optimized by the introduction of an online conductivity measurement. |
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Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solventsamorphous solid dispersionscoprecipitationhollow fiber membranescrossflow filtrationspray drying“brick-dust”Domínio/Área Científica::Engenharia e Tecnologia::Engenharia QuímicaCurrently, about 90% of drugs in development stages present poor-aqueous solubility, belonging to Biopharmaceutics Classification System (BCS) Classes II and IV. A leading technology to improve solubility is the production of amorphous solid dispersions (ASDs). ASDs are typically manufactured by spray drying (SD) and hot melt extrusion (HME), however these techniques are not suitable for “brick-dust” compounds. Coprecipitation is an adequate technology to deal with “brick-dust” compounds, since high boiling point solvents, with higher solubilization power, can be employed. This technology is not without drawbacks: the high volume and low solids’ load of the resultant suspension and the challenging drying of non-volatile organic solvents. With this work, these drawbacks are tackled through a proof-of-concept by incorporating crossflow filtration with hollow fiber membranes after coprecipitation to 1) concentrate the suspension, increasing solids’ load and 2) minimize the presence of the organic solvent, by diafiltration. Coprecipitation was carried out through two different techniques: high shear mixer and high-pressure homogenization (HPH). The suspensions were concentrated and washed in hollow fiber membranes unit and isolated through spray drying. Spray-dried ASDs were also produced to serve as benchmark against the coprecipitated prototypes. Coprecipitated prototypes and SD benchmarks were analytically characterized and the preliminary results seem to indicate a greater dissolution behavior of the HPH prototype. In conclusion, this study demonstrated the advantages of including a cross-filtration with hollow fiber membranes, a straightforward and scalable technology that allows the circumvention of typical pitfalls of the production of “brick-dust” ASDs by coprecipitation. In 60 minutes, the concentration step reduced the mass of HPH suspension to a half, and the diafiltration operations lowered the DSMO initial content in approximately 50% within 112 minutes; although this last step should be optimized by the introduction of an online conductivity measurement.Silva, RuiRicardo, AnaRUNMota, Rute Marina Faria2023-12-01T01:30:36Z2021-01-2620202021-01-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/111051enginfo: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:RCAAP2024-03-11T04:54:51Zoai:run.unl.pt:10362/111051Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:41:46.657180Repositório 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 |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
title |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
spellingShingle |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents Mota, Rute Marina Faria amorphous solid dispersions coprecipitation hollow fiber membranes crossflow filtration spray drying “brick-dust” Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química |
title_short |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
title_full |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
title_fullStr |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
title_full_unstemmed |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
title_sort |
Leveraging cross-filtration membranes to extend the production of amorphous solid dispersions (ASDs) to non-volatile organic solvents |
author |
Mota, Rute Marina Faria |
author_facet |
Mota, Rute Marina Faria |
author_role |
author |
dc.contributor.none.fl_str_mv |
Silva, Rui Ricardo, Ana RUN |
dc.contributor.author.fl_str_mv |
Mota, Rute Marina Faria |
dc.subject.por.fl_str_mv |
amorphous solid dispersions coprecipitation hollow fiber membranes crossflow filtration spray drying “brick-dust” Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química |
topic |
amorphous solid dispersions coprecipitation hollow fiber membranes crossflow filtration spray drying “brick-dust” Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química |
description |
Currently, about 90% of drugs in development stages present poor-aqueous solubility, belonging to Biopharmaceutics Classification System (BCS) Classes II and IV. A leading technology to improve solubility is the production of amorphous solid dispersions (ASDs). ASDs are typically manufactured by spray drying (SD) and hot melt extrusion (HME), however these techniques are not suitable for “brick-dust” compounds. Coprecipitation is an adequate technology to deal with “brick-dust” compounds, since high boiling point solvents, with higher solubilization power, can be employed. This technology is not without drawbacks: the high volume and low solids’ load of the resultant suspension and the challenging drying of non-volatile organic solvents. With this work, these drawbacks are tackled through a proof-of-concept by incorporating crossflow filtration with hollow fiber membranes after coprecipitation to 1) concentrate the suspension, increasing solids’ load and 2) minimize the presence of the organic solvent, by diafiltration. Coprecipitation was carried out through two different techniques: high shear mixer and high-pressure homogenization (HPH). The suspensions were concentrated and washed in hollow fiber membranes unit and isolated through spray drying. Spray-dried ASDs were also produced to serve as benchmark against the coprecipitated prototypes. Coprecipitated prototypes and SD benchmarks were analytically characterized and the preliminary results seem to indicate a greater dissolution behavior of the HPH prototype. In conclusion, this study demonstrated the advantages of including a cross-filtration with hollow fiber membranes, a straightforward and scalable technology that allows the circumvention of typical pitfalls of the production of “brick-dust” ASDs by coprecipitation. In 60 minutes, the concentration step reduced the mass of HPH suspension to a half, and the diafiltration operations lowered the DSMO initial content in approximately 50% within 112 minutes; although this last step should be optimized by the introduction of an online conductivity measurement. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2021-01-26 2021-01-26T00:00:00Z 2023-12-01T01:30:36Z |
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/10362/111051 |
url |
http://hdl.handle.net/10362/111051 |
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 |
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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