Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays

Autores
Gualdesi, María Soledad; Ravetti, Soledad; Raviolo, Mónica Ana; Briñon, Margarita Cristina
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
As a part of preformulation studies, the aim of this work was to examine the solubility and stability of a series of 50 -O-carbonates of lamivudine with proven antihuman immunodeficiency virus activity. Solubility studies were carried out using pure solvents (water, ethanol and polyethylene glycol 400 [PEG 400]), as well as cosolvents in binary mixture systems (water– ethanol and water–PEG 400). These ionizable compounds showed that their aqueous solubility is decreasing as the carbon length of the substituent moiety increases, but being enhanced as the pH was reduced from 7.4 to 1.2. Thus, 3TC-Metha an active compound of the series, with an intrinsic solubility at 25 C of 17 mg/mL, was about 70 times more soluble than 3TC-Octa (0.24 mg/mL), and at pHs of 1.2, 5.8 and 7.4 had intrinsic solubilities of 36.48, 19.20 and 15.40 mg/mL, respectively. In addition, the solubility was enhanced significantly by using ethanol and PEG 400 as cosolvents. A stability study was conducted in buffer solutions at pH 1.2, 5.8, 7.4 and 13.0 and in human plasma at 37 C. Stability-indicating high-performance liquid chromatography procedure was found to be selective, sensitive and accurate for these compounds and good recovery, linearity and precision were also observed.
Fil: Gualdesi, María Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ravetti, Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Raviolo, Mónica Ana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Briñon, Margarita Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Materia
Aqueous Stability
Cosolvency
Human Plasma Stability
Ph-Solubility Profiles
Prodrugs
Solubility
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/23544
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assaysGualdesi, María SoledadRavetti, SoledadRaviolo, Mónica AnaBriñon, Margarita CristinaAqueous StabilityCosolvencyHuman Plasma StabilityPh-Solubility ProfilesProdrugsSolubilityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1As a part of preformulation studies, the aim of this work was to examine the solubility and stability of a series of 50 -O-carbonates of lamivudine with proven antihuman immunodeficiency virus activity. Solubility studies were carried out using pure solvents (water, ethanol and polyethylene glycol 400 [PEG 400]), as well as cosolvents in binary mixture systems (water– ethanol and water–PEG 400). These ionizable compounds showed that their aqueous solubility is decreasing as the carbon length of the substituent moiety increases, but being enhanced as the pH was reduced from 7.4 to 1.2. Thus, 3TC-Metha an active compound of the series, with an intrinsic solubility at 25 C of 17 mg/mL, was about 70 times more soluble than 3TC-Octa (0.24 mg/mL), and at pHs of 1.2, 5.8 and 7.4 had intrinsic solubilities of 36.48, 19.20 and 15.40 mg/mL, respectively. In addition, the solubility was enhanced significantly by using ethanol and PEG 400 as cosolvents. A stability study was conducted in buffer solutions at pH 1.2, 5.8, 7.4 and 13.0 and in human plasma at 37 C. Stability-indicating high-performance liquid chromatography procedure was found to be selective, sensitive and accurate for these compounds and good recovery, linearity and precision were also observed.Fil: Gualdesi, María Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ravetti, Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Raviolo, Mónica Ana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Briñon, Margarita Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaTaylor & Francis2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/23544Gualdesi, María Soledad; Ravetti, Soledad; Raviolo, Mónica Ana; Briñon, Margarita Cristina; Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays; Taylor & Francis; Drug Development and Industrial Pharmacy; 40; 9; 7-2013; 1246-12520363-90451520-5762CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3109/03639045.2013.814064info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/03639045.2013.814064info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:16Zoai:ri.conicet.gov.ar:11336/23544instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:00:16.985CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
title Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
spellingShingle Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
Gualdesi, María Soledad
Aqueous Stability
Cosolvency
Human Plasma Stability
Ph-Solubility Profiles
Prodrugs
Solubility
title_short Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
title_full Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
title_fullStr Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
title_full_unstemmed Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
title_sort Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays
dc.creator.none.fl_str_mv Gualdesi, María Soledad
Ravetti, Soledad
Raviolo, Mónica Ana
Briñon, Margarita Cristina
author Gualdesi, María Soledad
author_facet Gualdesi, María Soledad
Ravetti, Soledad
Raviolo, Mónica Ana
Briñon, Margarita Cristina
author_role author
author2 Ravetti, Soledad
Raviolo, Mónica Ana
Briñon, Margarita Cristina
author2_role author
author
author
dc.subject.none.fl_str_mv Aqueous Stability
Cosolvency
Human Plasma Stability
Ph-Solubility Profiles
Prodrugs
Solubility
topic Aqueous Stability
Cosolvency
Human Plasma Stability
Ph-Solubility Profiles
Prodrugs
Solubility
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv As a part of preformulation studies, the aim of this work was to examine the solubility and stability of a series of 50 -O-carbonates of lamivudine with proven antihuman immunodeficiency virus activity. Solubility studies were carried out using pure solvents (water, ethanol and polyethylene glycol 400 [PEG 400]), as well as cosolvents in binary mixture systems (water– ethanol and water–PEG 400). These ionizable compounds showed that their aqueous solubility is decreasing as the carbon length of the substituent moiety increases, but being enhanced as the pH was reduced from 7.4 to 1.2. Thus, 3TC-Metha an active compound of the series, with an intrinsic solubility at 25 C of 17 mg/mL, was about 70 times more soluble than 3TC-Octa (0.24 mg/mL), and at pHs of 1.2, 5.8 and 7.4 had intrinsic solubilities of 36.48, 19.20 and 15.40 mg/mL, respectively. In addition, the solubility was enhanced significantly by using ethanol and PEG 400 as cosolvents. A stability study was conducted in buffer solutions at pH 1.2, 5.8, 7.4 and 13.0 and in human plasma at 37 C. Stability-indicating high-performance liquid chromatography procedure was found to be selective, sensitive and accurate for these compounds and good recovery, linearity and precision were also observed.
Fil: Gualdesi, María Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ravetti, Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Raviolo, Mónica Ana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Briñon, Margarita Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
description As a part of preformulation studies, the aim of this work was to examine the solubility and stability of a series of 50 -O-carbonates of lamivudine with proven antihuman immunodeficiency virus activity. Solubility studies were carried out using pure solvents (water, ethanol and polyethylene glycol 400 [PEG 400]), as well as cosolvents in binary mixture systems (water– ethanol and water–PEG 400). These ionizable compounds showed that their aqueous solubility is decreasing as the carbon length of the substituent moiety increases, but being enhanced as the pH was reduced from 7.4 to 1.2. Thus, 3TC-Metha an active compound of the series, with an intrinsic solubility at 25 C of 17 mg/mL, was about 70 times more soluble than 3TC-Octa (0.24 mg/mL), and at pHs of 1.2, 5.8 and 7.4 had intrinsic solubilities of 36.48, 19.20 and 15.40 mg/mL, respectively. In addition, the solubility was enhanced significantly by using ethanol and PEG 400 as cosolvents. A stability study was conducted in buffer solutions at pH 1.2, 5.8, 7.4 and 13.0 and in human plasma at 37 C. Stability-indicating high-performance liquid chromatography procedure was found to be selective, sensitive and accurate for these compounds and good recovery, linearity and precision were also observed.
publishDate 2013
dc.date.none.fl_str_mv 2013-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/23544
Gualdesi, María Soledad; Ravetti, Soledad; Raviolo, Mónica Ana; Briñon, Margarita Cristina; Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays; Taylor & Francis; Drug Development and Industrial Pharmacy; 40; 9; 7-2013; 1246-1252
0363-9045
1520-5762
CONICET Digital
CONICET
url http://hdl.handle.net/11336/23544
identifier_str_mv Gualdesi, María Soledad; Ravetti, Soledad; Raviolo, Mónica Ana; Briñon, Margarita Cristina; Preformulation studies of novel 5′-O-carbonates of lamivudine with biological activity: solubility and stability assays; Taylor & Francis; Drug Development and Industrial Pharmacy; 40; 9; 7-2013; 1246-1252
0363-9045
1520-5762
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3109/03639045.2013.814064
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/03639045.2013.814064
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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