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Previous issue date: 2013-08-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Atualmente, os medicamentos utilizados em crian?as s?o adaptados a partir de
formas farmac?uticas s?lidas desenvolvidas para adultos. O captopril ? amplamente
adaptado para formula??o l?quida em hospitais. Sua estabilidade em meio aquoso ?
reduzida, pois sofre oxida??o gerando o dissulfeto de captopril. Com o intuito de
garantir a estabilidade do f?rmaco e dosagem precisa, foi desenvolvido um estudo
de pr?-formula??o para a obten??o de uma formula??o de captopril em p? para
constitui??o de uma solu??o est?vel de uso pedi?trico. A compatibilidade entre o
f?rmaco e os poss?veis excipientes foi avaliada atrav?s das an?lises de calorimetria
de varredura diferencial (DSC) e o comportamento t?rmico do captopril atrav?s das
an?lises termogravim?tica (TG) e t?rmica diferencial (DTA). Em seguida, foram
realizados os ensaios de an?lise granulom?trica e das medidas indiretas de fluxo do
captopril e dos excipientes. Para estudo em solu??o, foram obtidas diferentes
formula??es a partir de planejamento fatorial, em que se variou a concentra??o de
EDTA (0,005 e 0,1%) e pH (2,5; 4,0 e 5,5) em ?gua destilada e ?gua mineral, que
foram armazenadas a 60?C e analisadas ao longo de doze dias por CLAE para
avalia??o da estabilidade do captopril. Nas curvas DSC das misturas de captotpril
com os conservantes, a sucralose e o ?cido c?trico, os eventos t?rmicos de cada
subst?ncia isolada n?o foram mantidos. Nas demais curvas das misturas bin?rias os
eventos correspondentes a cada componente foram preservados, indicando
compatibilidade entre as subst?ncias. Foi observada uma grande diferen?a na
distribui??o e di?metro m?dio das part?culas e densidade dos agentes tamponantes
em compara??o ?s demais subst?ncias, o que pode ocasionar a segrega??o da
mistura de p?s. A partir do estudo da estabilidade das solu??es, foi verificado que as
vari?veis interferem significativamente (p = 0,05) no teor do captopril, sendo o pH o
fator mais relevante. As intera??es entre as vari?veis foram significativas, com maior
estabilidade observada em pH pr?ximo a 4,0, maior concentra??o de EDTA e uso de
?gua mineral. Com base nos resultados, pode-se concluir que o desenvolvimento de
uma formula??o de captopril est?vel ? vi?vel desde que sejam adotadas medidas
estrat?gicas a fim de se evitar a segrega??o dos p?s constituintes da formula??o. / Nowadays, drugs used in children are adapted from solid dosage forms developed
for adults. Captopril in solid dosage form is widely adapted in hospitals into a liquid
formulation. Its stability in aqueous solutions is reduced because it undergoes
oxidation, forming captopril disulfide. In order to ensure a stable and accurate dosage
form, a pre-formulation study was developed for obtaining a stable formulation of a
powder for preparation of a captopril solution for pediatric use. The compatibility
between drug and possible excipients were evaluated by differential scanning
calorimetry (DSC) and the captopril thermic behavior, through thermogravimetric
analysis (TG) and differential thermal analysis (DTA). Then, particle size and indirect
flow measures of captopril and excipients were analyzed. For solution studies,
different formulations were obtained through factorial design, varying the EDTA
concentration (0.005 and 0.1%) and pH (2.5, 4.0 e 5.5) in distilled and mineral water,
which were stored at 60?C and analyzed over twelve days by HPLC to evaluate the
stability of captopril. In the DSC curves of captopril mixtures with preservatives,
sucralose and citric acid, the isolated thermal events were not maintained. In the
other binary mixtures, the events corresponding to each component were preserved
in the curves, indicating compatibility between substances. There was a major
difference in the distribution and average particles diameters and density of buffering
agents in comparison to other substances, which can cause segregation of the
powder mixture. From the study of the solutions stability it was found that the
variables interfere significantly (p = 0.05) in the captopril content, the pH being the
most important factor. The interactions between variables were significant, with
greater stability around pH 4.0, higher EDTA concentrations and use of mineral
water. Based on the results, it can be concluded that development of a stable
captopril formulation is viable if strategic measures are adopted in order to avoid
segregation of the powders constituents of the formulation.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/21710 |
| Date | 29 August 2013 |
| Creators | Goes, Janaina da Silva |
| Contributors | 60253991404, Morais, Waldenice de Alencar, 03431763430, Fonteles, Marta Maria de Fran?a, 28529839315, Arag?o, Cicero Fl?vio Soares, Raffin, Fernanda Nervo |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS FARMAC?UTICAS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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