Estudo de pré-formulação para a obtenção de uma formulação de captopril para uso pediátrico
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 t...
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| Formato: | Dissertação |
| Idioma: | por |
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/21710 |
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| Resumo: | 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. |
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