Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach

Autores
Santos Souza, Higo Fernando; Real, Daniel Andres; Leonardi, Darío; Rocha, Sandra Carla; Alonso, Victoria Lucia; Serra, Esteban Carlos; Silber, Ariel Mariano; Salomon, Claudio Javier
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. Methods: In a quality-by-design approach, a systematic optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in vivo palatability assay. Mice were infected and treated orally in a murine model. Results: The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimised co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In vivo studies showed that both parasitaemia and mortality diminished, particularly at a dose of 40 mg/kg/day. Conclusion: Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.
Fil: Santos Souza, Higo Fernando. Universidade de Sao Paulo; Brasil
Fil: Real, Daniel Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; Argentina
Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; Argentina
Fil: Rocha, Sandra Carla. Universidade de Sao Paulo; Brasil
Fil: Alonso, Victoria Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; Argentina
Fil: Serra, Esteban Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; Argentina
Fil: Silber, Ariel Mariano. Universidade de Sao Paulo; Brasil
Fil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Area Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Materia
Benznidazole
Chagas Disease
Co-Solvency
In Vivo Study
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:11336/50459
Acceder
id CONICETDig_90c758559f74128b1c5cda0c89ee580c
oai_identifier_str oai:ri.conicet.gov.ar:11336/50459
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approachSantos Souza, Higo FernandoReal, Daniel AndresLeonardi, DaríoRocha, Sandra CarlaAlonso, Victoria LuciaSerra, Esteban CarlosSilber, Ariel MarianoSalomon, Claudio JavierBenznidazoleChagas DiseaseCo-SolvencyIn Vivo StudySolubilityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Objectives: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. Methods: In a quality-by-design approach, a systematic optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in vivo palatability assay. Mice were infected and treated orally in a murine model. Results: The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimised co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In vivo studies showed that both parasitaemia and mortality diminished, particularly at a dose of 40 mg/kg/day. Conclusion: Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.Fil: Santos Souza, Higo Fernando. Universidade de Sao Paulo; BrasilFil: Real, Daniel Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; ArgentinaFil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; ArgentinaFil: Rocha, Sandra Carla. Universidade de Sao Paulo; BrasilFil: Alonso, Victoria Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; ArgentinaFil: Serra, Esteban Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; ArgentinaFil: Silber, Ariel Mariano. Universidade de Sao Paulo; BrasilFil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Area Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaWiley Blackwell Publishing, Inc2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50459Santos Souza, Higo Fernando; Real, Daniel Andres; Leonardi, Darío; Rocha, Sandra Carla; Alonso, Victoria Lucia; et al.; Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach; Wiley Blackwell Publishing, Inc; Tropical Medicine And International Health; 22; 12; 12-2017; 1514-15221360-2276CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/tmi.12980info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/tmi.12980info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:17Zoai:ri.conicet.gov.ar:11336/50459instacron: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 09:51:17.779CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
title Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
spellingShingle Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
Santos Souza, Higo Fernando
Benznidazole
Chagas Disease
Co-Solvency
In Vivo Study
Solubility
title_short Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
title_full Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
title_fullStr Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
title_full_unstemmed Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
title_sort Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
dc.creator.none.fl_str_mv Santos Souza, Higo Fernando
Real, Daniel Andres
Leonardi, Darío
Rocha, Sandra Carla
Alonso, Victoria Lucia
Serra, Esteban Carlos
Silber, Ariel Mariano
Salomon, Claudio Javier
author Santos Souza, Higo Fernando
author_facet Santos Souza, Higo Fernando
Real, Daniel Andres
Leonardi, Darío
Rocha, Sandra Carla
Alonso, Victoria Lucia
Serra, Esteban Carlos
Silber, Ariel Mariano
Salomon, Claudio Javier
author_role author
author2 Real, Daniel Andres
Leonardi, Darío
Rocha, Sandra Carla
Alonso, Victoria Lucia
Serra, Esteban Carlos
Silber, Ariel Mariano
Salomon, Claudio Javier
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Benznidazole
Chagas Disease
Co-Solvency
In Vivo Study
Solubility
topic Benznidazole
Chagas Disease
Co-Solvency
In Vivo Study
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 Objectives: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. Methods: In a quality-by-design approach, a systematic optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in vivo palatability assay. Mice were infected and treated orally in a murine model. Results: The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimised co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In vivo studies showed that both parasitaemia and mortality diminished, particularly at a dose of 40 mg/kg/day. Conclusion: Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.
Fil: Santos Souza, Higo Fernando. Universidade de Sao Paulo; Brasil
Fil: Real, Daniel Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; Argentina
Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; Argentina
Fil: Rocha, Sandra Carla. Universidade de Sao Paulo; Brasil
Fil: Alonso, Victoria Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; Argentina
Fil: Serra, Esteban Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; Argentina
Fil: Silber, Ariel Mariano. Universidade de Sao Paulo; Brasil
Fil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Area Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
description Objectives: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. Methods: In a quality-by-design approach, a systematic optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in vivo palatability assay. Mice were infected and treated orally in a murine model. Results: The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimised co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In vivo studies showed that both parasitaemia and mortality diminished, particularly at a dose of 40 mg/kg/day. Conclusion: Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
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/11336/50459
Santos Souza, Higo Fernando; Real, Daniel Andres; Leonardi, Darío; Rocha, Sandra Carla; Alonso, Victoria Lucia; et al.; Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach; Wiley Blackwell Publishing, Inc; Tropical Medicine And International Health; 22; 12; 12-2017; 1514-1522
1360-2276
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50459
identifier_str_mv Santos Souza, Higo Fernando; Real, Daniel Andres; Leonardi, Darío; Rocha, Sandra Carla; Alonso, Victoria Lucia; et al.; Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach; Wiley Blackwell Publishing, Inc; Tropical Medicine And International Health; 22; 12; 12-2017; 1514-1522
1360-2276
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/tmi.12980
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/tmi.12980
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
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
_version_ 1842269086405361664
score 13.13397

Publicaciones similares