Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/26696 |
Resumo: | Brazil is one of the countries with the highest prevalence of congenital toxoplasmosis in the world and the treatment of the infection is done through the association of sulfadiazine (SDZ), pyrimethamine and folinic acid. However, SDZ is commercially available only astablets, which turns difficult the treatment of children. In this context, the objective of this work was to develop and to determine the stability of formulations for pediatric use, with adequate characteristics and excipients compatible with the age group. To achieve our goal, SDZ suspensions at 100 mg/mL were prepared, using the active pharmaceutical ingredient (API, suspension A) or crushed tablets (suspension B). The formulations were prepared, after careful choice of excipients and concentrations to be used and stored under refrigeration for 30 days for stability evaluation. The physical stability of the suspensions was analyzed through the organoleptic characteristics, pH, particle size and viscosity. The chemical stability was verified through the SDZ content, which was determined by an ultra-high performance liquid chromatography (UPLC) method developed and validated in this study. The dissolution of the formulations was also investigated, as well as the microbiological stability, for the latter it was necessary to inactivate the antimicrobial action of the formulation components, to avoid false-negative results. The pH of the suspensions remained in the neutrality range and unchanged during the study (p>0.05). It was observed a decrease in particle size during the study (p<0.05) for both formulations, as well as the formulation B (50,63 ± 2,65 μm) presented a significantly larger particle size than formulation A (35,2 ± 5,26 μm). Additionally, it was possible to identify the presence of crystals in suspension A, attributed to SDZ API, however, there was no change in this characteristic throughout the analysis period. Both formulations presented non-Newtonian flow and there was no statistically significant change in viscosity during 30 days. Suspensions A and B presented contents close to 100% without showing statistical variation, which proved the chemical stability of 30 days. In addition, they presented more than 80% dissolution in 15 minutes without statistically significant difference when compared to the percentage of SDZ dissolved in the beginning and at the end of the study, such as between formulations A and B. No microbial growth was observed (<10 CFU/mL) in both formulations, as well as the presence of Escherichia coli was not identified, that indicated that the developed formulations met the pharmacopeial requirements. The formulations developed in this study showed physical, chemical and microbiological stability for 30 days and may be an option for the treatment of congenital toxoplasmosis. |
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Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátricoDevelopment and stability study of sulfadiazine suspensions for pediatric useFormulação pediátricaSulfadiazinaSuspensãoToxoplasmose congênitaPediatric formulationSulfadiazineSuspensionCongenital toxoplasmosisCNPQ::CIENCIAS DA SAUDE::FARMACIABrazil is one of the countries with the highest prevalence of congenital toxoplasmosis in the world and the treatment of the infection is done through the association of sulfadiazine (SDZ), pyrimethamine and folinic acid. However, SDZ is commercially available only astablets, which turns difficult the treatment of children. In this context, the objective of this work was to develop and to determine the stability of formulations for pediatric use, with adequate characteristics and excipients compatible with the age group. To achieve our goal, SDZ suspensions at 100 mg/mL were prepared, using the active pharmaceutical ingredient (API, suspension A) or crushed tablets (suspension B). The formulations were prepared, after careful choice of excipients and concentrations to be used and stored under refrigeration for 30 days for stability evaluation. The physical stability of the suspensions was analyzed through the organoleptic characteristics, pH, particle size and viscosity. The chemical stability was verified through the SDZ content, which was determined by an ultra-high performance liquid chromatography (UPLC) method developed and validated in this study. The dissolution of the formulations was also investigated, as well as the microbiological stability, for the latter it was necessary to inactivate the antimicrobial action of the formulation components, to avoid false-negative results. The pH of the suspensions remained in the neutrality range and unchanged during the study (p>0.05). It was observed a decrease in particle size during the study (p<0.05) for both formulations, as well as the formulation B (50,63 ± 2,65 μm) presented a significantly larger particle size than formulation A (35,2 ± 5,26 μm). Additionally, it was possible to identify the presence of crystals in suspension A, attributed to SDZ API, however, there was no change in this characteristic throughout the analysis period. Both formulations presented non-Newtonian flow and there was no statistically significant change in viscosity during 30 days. Suspensions A and B presented contents close to 100% without showing statistical variation, which proved the chemical stability of 30 days. In addition, they presented more than 80% dissolution in 15 minutes without statistically significant difference when compared to the percentage of SDZ dissolved in the beginning and at the end of the study, such as between formulations A and B. No microbial growth was observed (<10 CFU/mL) in both formulations, as well as the presence of Escherichia coli was not identified, that indicated that the developed formulations met the pharmacopeial requirements. The formulations developed in this study showed physical, chemical and microbiological stability for 30 days and may be an option for the treatment of congenital toxoplasmosis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO Brasil é um dos países com maior prevalência de toxoplasmose congênita do mundo e o tratamento da infecção é feito através da associação de sulfadiazina (SDZ), pirimetamina e ácido folínico. Entretanto, a SDZ encontra-se disponível comercialmente apenas na forma de comprimidos, o que dificulta o tratamento em crianças acometidas pela doença. Nesse contexto, o objetivo deste trabalho foi desenvolver e avaliar a estabilidade de formulações para uso pediátrico, que apresentem características adequadas e excipientes compatíveis com a faixa etária. Para tal, foram preparadas suspensões de SDZ 100 mg/mL obtidas a partir do insumo farmacêutico ativo (suspensão A) e de comprimidos triturados (suspensão B). As formulações foram elaboradas, após cautelosa escolha dos excipientes e das concentrações a serem utilizadas, e armazenadas sob refrigeração, durante 30 dias para avaliação da estabilidade. A estabilidade física das suspensões foi analisada através das características organolépticas, pH, tamanho e morfologia das partículas e viscosidade, bem como, a estabilidade química foi verificada através do teor de SDZ, o qual foi determinado mediante aplicação do método desenvolvido e validado por cromatografia a líquido de ultra eficiência (CLUE). A dissolução das formulações também foi investigada, assim como, a estabilidade microbiológica, sendo que para esta última foi necessário inativar a ação antimicrobiana dos componentes da formulação a fim de evitar resultados falso-negativos. O pH das suspensões manteve-se na faixa da neutralidade e inalterado durante o estudo (p>0,05). Houve diminuição do tamanho de partícula em cada formulação ao longo do tempo, sendo que a formulação B (50,63 ± 2,65 μm) apresentou tamanho de partícula significativamente maior em relação à formulação A (35,2 ± 5,26 μm). Adicionalmente, foi possível identificar a presença de cristais na suspensão A, advindos da própria SDZ, entretanto, não houve alteração dessa característica ao longo do período de análise. Ambas as formulações se apresentaram-se como fluidos não-Newtonianos e não houve alteração estatisticamente significativa na viscosidade, durante 30 dias. As suspensões A e B apresentaram teores próximos de 100% sem apresentar variação estatística, o que comprovou a estabilidade química de 30 dias. Além disso, apresentaram mais de 80% de dissolução em 15 minutos, sem diferença estatística significativa quando comparadas as porcentagens de SDZ dissolvida logo após a preparação e ao final do estudo, assim como, entre as formulações A e B. Não foi observado crescimento microbiano (<10 UFC/mL) em ambas as formulações, assim como, não foi identificada a presença de Escherichia coli, indicando que as formulações atendem aos padrões microbianos. As formulações desenvolvidas nesse estudo apresentaram estabilidade física, química e microbiológica de 30 dias, mantidas sob refrigeração, e consistem em opção para o tratamento da toxoplasmose congênita.Universidade Federal de Santa MariaBrasilFarmáciaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeAdams, Andréa Inês Hornhttp://lattes.cnpq.br/6872246935204149Ferreira, Luana MotaBajerski, LisianeSilva, Cristiane de Bona daDias, Micheline Silva2022-10-27T18:22:11Z2022-10-27T18:22:11Z2022-02-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/26696porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-10-27T18:22:11Zoai:repositorio.ufsm.br:1/26696Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-27T18:22:11Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico Development and stability study of sulfadiazine suspensions for pediatric use |
title |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico |
spellingShingle |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico Dias, Micheline Silva Formulação pediátrica Sulfadiazina Suspensão Toxoplasmose congênita Pediatric formulation Sulfadiazine Suspension Congenital toxoplasmosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico |
title_full |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico |
title_fullStr |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico |
title_full_unstemmed |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico |
title_sort |
Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico |
author |
Dias, Micheline Silva |
author_facet |
Dias, Micheline Silva |
author_role |
author |
dc.contributor.none.fl_str_mv |
Adams, Andréa Inês Horn http://lattes.cnpq.br/6872246935204149 Ferreira, Luana Mota Bajerski, Lisiane Silva, Cristiane de Bona da |
dc.contributor.author.fl_str_mv |
Dias, Micheline Silva |
dc.subject.por.fl_str_mv |
Formulação pediátrica Sulfadiazina Suspensão Toxoplasmose congênita Pediatric formulation Sulfadiazine Suspension Congenital toxoplasmosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Formulação pediátrica Sulfadiazina Suspensão Toxoplasmose congênita Pediatric formulation Sulfadiazine Suspension Congenital toxoplasmosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Brazil is one of the countries with the highest prevalence of congenital toxoplasmosis in the world and the treatment of the infection is done through the association of sulfadiazine (SDZ), pyrimethamine and folinic acid. However, SDZ is commercially available only astablets, which turns difficult the treatment of children. In this context, the objective of this work was to develop and to determine the stability of formulations for pediatric use, with adequate characteristics and excipients compatible with the age group. To achieve our goal, SDZ suspensions at 100 mg/mL were prepared, using the active pharmaceutical ingredient (API, suspension A) or crushed tablets (suspension B). The formulations were prepared, after careful choice of excipients and concentrations to be used and stored under refrigeration for 30 days for stability evaluation. The physical stability of the suspensions was analyzed through the organoleptic characteristics, pH, particle size and viscosity. The chemical stability was verified through the SDZ content, which was determined by an ultra-high performance liquid chromatography (UPLC) method developed and validated in this study. The dissolution of the formulations was also investigated, as well as the microbiological stability, for the latter it was necessary to inactivate the antimicrobial action of the formulation components, to avoid false-negative results. The pH of the suspensions remained in the neutrality range and unchanged during the study (p>0.05). It was observed a decrease in particle size during the study (p<0.05) for both formulations, as well as the formulation B (50,63 ± 2,65 μm) presented a significantly larger particle size than formulation A (35,2 ± 5,26 μm). Additionally, it was possible to identify the presence of crystals in suspension A, attributed to SDZ API, however, there was no change in this characteristic throughout the analysis period. Both formulations presented non-Newtonian flow and there was no statistically significant change in viscosity during 30 days. Suspensions A and B presented contents close to 100% without showing statistical variation, which proved the chemical stability of 30 days. In addition, they presented more than 80% dissolution in 15 minutes without statistically significant difference when compared to the percentage of SDZ dissolved in the beginning and at the end of the study, such as between formulations A and B. No microbial growth was observed (<10 CFU/mL) in both formulations, as well as the presence of Escherichia coli was not identified, that indicated that the developed formulations met the pharmacopeial requirements. The formulations developed in this study showed physical, chemical and microbiological stability for 30 days and may be an option for the treatment of congenital toxoplasmosis. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-10-27T18:22:11Z 2022-10-27T18:22:11Z 2022-02-18 |
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://repositorio.ufsm.br/handle/1/26696 |
url |
http://repositorio.ufsm.br/handle/1/26696 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922108432187392 |