Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/29584 |
Resumo: | Toxoplasmosis is a zoonosis with worldwide distribution, which can be transmitted to the fetus during pregnancy. The child's treatment should start just after birth and consists of pyrimethamine (PYM), sulfadiazine, and folinic acid. However, PYM is commercially available only as tablets, which difficult the treatment of children. In this context, this study aimed to verify the feasibility of obtaining oral suspensions of PYM, suitable for all pediatric age groups. Two PYM suspensions were prepared: suspension A (with preservative, methylparaben - MP) and suspension B (without preservative), from commercially obtained tablets. The excipients and their concentrations were carefully chosen to obtain safe products for the intended age group. Physicochemical characteristics such as pH, particle size, zeta potential, viscosity, dissolution, and PYM and (MP) content were evaluated using an ultraperformance liquid chromatography (UPLC) method validated during the study, following the current guidelines. Concerning the microbiological evaluation, the count of mesophilic microorganisms and the absence of E. coli were determined. For the stability study, suspension A was evaluated for 42 days, stored under refrigeration or at room temperature (20 to 25ºC). Suspension B was kept under refrigeration and analyzed for 7 days. The results obtained indicated that the CLUE method was accurate, precise, linear, robust, specific, and suitable for use in stability studies. The formulations showed pH values in the range of 7.1 to 7.9, particle size in the range of 50 to 65 µm, and zeta potential in the range of -50 to -65 mV; these characteristics remained constant throughout the study. The formulations were characterized as non-Newtonian fluids, with pseudoplastic behavior, presenting thixotropy. In addition, there was a decrease in the formulation viscosity in the final analysis. The formulation dissolution was greater than 90% at 30 minutes, remaining constant throughout the study. There was a small decrease in PYM and MP levels throughout the study, with no evidence of a significant difference considering the initial time. Regarding the bioburden, suspension A, under both storage conditions, met the pharmacopeial specification, with bacterial and fungal counting < 10 CFU/mL and an absence of E. coli until the end of the study. Suspension B, in turn, met the requirements of bacteria and fungi count until the 4th day. Regarding E. coli, there was no growth until the 7th day. The results indicated the viability of obtaining the formulation; suspension A showed physicochemical and microbiological stability for 42 days, using a single preservative at a low concentration. Suspension B, focused on the treatment of neonates, can be used for up to four days without impairing the physicochemical characteristics and without microbial contamination. Both formulations are alternatives for the treatment of congenital toxoplasmosis. |
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Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátricoDevelopment and stability study of pyrimethamine suspensions for pediatric usePirimetaminaSuspensãoPreparações extemporâneasToxoplasmose congênitaPyrimethamineSuspensionExtemporaneous preparationsCongenital toxoplasmosisCNPQ::CIENCIAS DA SAUDE::FARMACIAToxoplasmosis is a zoonosis with worldwide distribution, which can be transmitted to the fetus during pregnancy. The child's treatment should start just after birth and consists of pyrimethamine (PYM), sulfadiazine, and folinic acid. However, PYM is commercially available only as tablets, which difficult the treatment of children. In this context, this study aimed to verify the feasibility of obtaining oral suspensions of PYM, suitable for all pediatric age groups. Two PYM suspensions were prepared: suspension A (with preservative, methylparaben - MP) and suspension B (without preservative), from commercially obtained tablets. The excipients and their concentrations were carefully chosen to obtain safe products for the intended age group. Physicochemical characteristics such as pH, particle size, zeta potential, viscosity, dissolution, and PYM and (MP) content were evaluated using an ultraperformance liquid chromatography (UPLC) method validated during the study, following the current guidelines. Concerning the microbiological evaluation, the count of mesophilic microorganisms and the absence of E. coli were determined. For the stability study, suspension A was evaluated for 42 days, stored under refrigeration or at room temperature (20 to 25ºC). Suspension B was kept under refrigeration and analyzed for 7 days. The results obtained indicated that the CLUE method was accurate, precise, linear, robust, specific, and suitable for use in stability studies. The formulations showed pH values in the range of 7.1 to 7.9, particle size in the range of 50 to 65 µm, and zeta potential in the range of -50 to -65 mV; these characteristics remained constant throughout the study. The formulations were characterized as non-Newtonian fluids, with pseudoplastic behavior, presenting thixotropy. In addition, there was a decrease in the formulation viscosity in the final analysis. The formulation dissolution was greater than 90% at 30 minutes, remaining constant throughout the study. There was a small decrease in PYM and MP levels throughout the study, with no evidence of a significant difference considering the initial time. Regarding the bioburden, suspension A, under both storage conditions, met the pharmacopeial specification, with bacterial and fungal counting < 10 CFU/mL and an absence of E. coli until the end of the study. Suspension B, in turn, met the requirements of bacteria and fungi count until the 4th day. Regarding E. coli, there was no growth until the 7th day. The results indicated the viability of obtaining the formulation; suspension A showed physicochemical and microbiological stability for 42 days, using a single preservative at a low concentration. Suspension B, focused on the treatment of neonates, can be used for up to four days without impairing the physicochemical characteristics and without microbial contamination. Both formulations are alternatives for the treatment of congenital toxoplasmosis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA toxoplasmose é uma zoonose de distribuição mundial, que pode ser transmitida para o feto durante a gestação. O tratamento da criança deve iniciar logo após o nascimento e é composto por pirimetamina (PYM), sulfadiazina e ácido folínico. Entretanto, a PYM é disponível comercialmente apenas como comprimidos, o que dificulta a administração a pacientes pediátricos. Nesse contexto, o objetivo deste trabalho foi verificar a viabilidade de obter suspensões orais de PYM, apropriadas para uso em todas as faixas etárias da pediatria. Foram preparadas duas suspensões de PYM: suspensão A (com conservante, metilparabeno - MP) e suspensão B (sem conservante), a partir de comprimidos obtidos comercialmente. Os excipientes e suas concentrações foram cuidadosamente escolhidos visando obter produtos seguros para a faixa etária pretendida. Foram avaliadas características físico-químicas como pH, tamanho de partícula, potencial zeta, viscosidade, dissolução e teor de PYM e MP, através de um método de cromatografia a líquido de ultra eficiência (CLUE) validado durante o estudo, conforme as diretrizes vigentes. Quanto à avaliação microbiológica, determinou-se a contagem de micro-organismos mesófilos e a ausência de E. coli. Para o estudo de estabilidade, a suspensão A foi avaliada por 42 dias, armazenada sob refrigeração ou em temperatura ambiente (20 a 25ºC). A suspensão B foi mantida sob refrigeração e analisada por 7 dias. Os resultados obtidos indicaram que o método de CLUE foi exato, preciso, linear, robusto, específico e apto para ser usado em estudos de estabilidade. As formulações apresentaram valores de pH na faixa de 7,1 a 7,9, tamanho de partícula na faixa de 50 a 65 µm, e potencial zeta na faixa de -50 a -65 mV; estas características permaneceram constantes ao longo do estudo. As formulações foram consideradas como fluidos não-Newtonianos, com comportamento pseudoplástico, apresentando tixotropia. Além disso, houve redução da viscosidade das formulações nos tempos finais de análise. A dissolução das formulações foi superior a 90% em 30 minutos, permanecendo constante ao longo do estudo. Houve um pequeno decréscimo nos teores de PYM e MP durante o armazenamento, mas sem evidência de diferença significativa em relação ao teor inicial. Em relação à carga microbiana, a suspensão A, em ambas as condições de armazenamento, atendeu a especificação farmacopeica, com contagem de bactérias e fungos < 10 UFC/mL e ausência de E. coli. A suspensão B, por sua vez, atendeu os requisitos de contagem de bactérias e fungos até o 4º dia de armazenamento. Em relação à E. coli, não houve crescimento até o 7º dia. Os resultados indicaram a viabilidade de obtenção das formulações; a suspensão A apresentou estabilidade físico-química e microbiológica de 42 dias, com uso de um único conservante, em baixa concentração. A suspensão B, focada no tratamento de neonatos, pode ser usada por até quatro dias sem prejuízo das características físico-químicas e sem contaminação microbiana. Ambas as formulações consistem em alternativas 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 MotaSteppe, MartinSilva, Cristiane de Bona daNeis, Julya Sarmento2023-06-30T16:01:09Z2023-06-30T16:01:09Z2023-03-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/29584porAttribution-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:UFSM2023-06-30T16:01:09Zoai:repositorio.ufsm.br:1/29584Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-06-30T16:01:09Manancial - 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 pirimetamina para uso pediátrico Development and stability study of pyrimethamine suspensions for pediatric use |
title |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico |
spellingShingle |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico Neis, Julya Sarmento Pirimetamina Suspensão Preparações extemporâneas Toxoplasmose congênita Pyrimethamine Suspension Extemporaneous preparations Congenital toxoplasmosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico |
title_full |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico |
title_fullStr |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico |
title_full_unstemmed |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico |
title_sort |
Desenvolvimento e estudo de estabilidade de suspensões de pirimetamina para uso pediátrico |
author |
Neis, Julya Sarmento |
author_facet |
Neis, Julya Sarmento |
author_role |
author |
dc.contributor.none.fl_str_mv |
Adams, Andréa Inês Horn http://lattes.cnpq.br/6872246935204149 Ferreira, Luana Mota Steppe, Martin Silva, Cristiane de Bona da |
dc.contributor.author.fl_str_mv |
Neis, Julya Sarmento |
dc.subject.por.fl_str_mv |
Pirimetamina Suspensão Preparações extemporâneas Toxoplasmose congênita Pyrimethamine Suspension Extemporaneous preparations Congenital toxoplasmosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Pirimetamina Suspensão Preparações extemporâneas Toxoplasmose congênita Pyrimethamine Suspension Extemporaneous preparations Congenital toxoplasmosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Toxoplasmosis is a zoonosis with worldwide distribution, which can be transmitted to the fetus during pregnancy. The child's treatment should start just after birth and consists of pyrimethamine (PYM), sulfadiazine, and folinic acid. However, PYM is commercially available only as tablets, which difficult the treatment of children. In this context, this study aimed to verify the feasibility of obtaining oral suspensions of PYM, suitable for all pediatric age groups. Two PYM suspensions were prepared: suspension A (with preservative, methylparaben - MP) and suspension B (without preservative), from commercially obtained tablets. The excipients and their concentrations were carefully chosen to obtain safe products for the intended age group. Physicochemical characteristics such as pH, particle size, zeta potential, viscosity, dissolution, and PYM and (MP) content were evaluated using an ultraperformance liquid chromatography (UPLC) method validated during the study, following the current guidelines. Concerning the microbiological evaluation, the count of mesophilic microorganisms and the absence of E. coli were determined. For the stability study, suspension A was evaluated for 42 days, stored under refrigeration or at room temperature (20 to 25ºC). Suspension B was kept under refrigeration and analyzed for 7 days. The results obtained indicated that the CLUE method was accurate, precise, linear, robust, specific, and suitable for use in stability studies. The formulations showed pH values in the range of 7.1 to 7.9, particle size in the range of 50 to 65 µm, and zeta potential in the range of -50 to -65 mV; these characteristics remained constant throughout the study. The formulations were characterized as non-Newtonian fluids, with pseudoplastic behavior, presenting thixotropy. In addition, there was a decrease in the formulation viscosity in the final analysis. The formulation dissolution was greater than 90% at 30 minutes, remaining constant throughout the study. There was a small decrease in PYM and MP levels throughout the study, with no evidence of a significant difference considering the initial time. Regarding the bioburden, suspension A, under both storage conditions, met the pharmacopeial specification, with bacterial and fungal counting < 10 CFU/mL and an absence of E. coli until the end of the study. Suspension B, in turn, met the requirements of bacteria and fungi count until the 4th day. Regarding E. coli, there was no growth until the 7th day. The results indicated the viability of obtaining the formulation; suspension A showed physicochemical and microbiological stability for 42 days, using a single preservative at a low concentration. Suspension B, focused on the treatment of neonates, can be used for up to four days without impairing the physicochemical characteristics and without microbial contamination. Both formulations are alternatives for the treatment of congenital toxoplasmosis. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-06-30T16:01:09Z 2023-06-30T16:01:09Z 2023-03-27 |
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/1/29584 |
url |
http://repositorio.ufsm.br/handle/1/29584 |
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 |
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1805922019453173760 |