Avaliação da estabilidade físico-química de suspensão oftálmica de cetoconazol
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Data
2022-04-29
Autores
Cardozo, Ramon de Oliveira
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Editor
Universidade Federal do Espírito Santo
Resumo
Ketoconazole is an antifungal that belongs to the imidazole class and has therapeutic potential for the treatment of many mycotic infections. The antifungal drugs used in ophthalmic clinics are polyenes, azoles and pyrimidine derivatives. Most of antifungals has been their formulations adapted systemically for topical ophthalmic use. The drug studied is the pharmaceutical active ingredient of a compounding medicine, as an ophthalmic suspension, with no information regarding its conservation, storage or in relation to the excipients used in the formula. Due to the absence of official monographs of ketoconazole ophthalmic suspension, the development and validation of the analytical methodology is justified, as well as the quality control including stability tests. The aim of this study was to evaluate the stability of ketoconazole ophthalmic suspension 5%, which is used in a public hospital in the State of Espírito Santo, Brazil. For the suspension pharmaceutical form, the Brazilian Pharmacopoeia 6th Edition method was adapted and the highperformance liquid chromatography analytical method was validated. For that, tests of accuracy, precision, selectivity, linearity, range, detection and quantification limit, and robustness were performed. In the analytical methodology were used methanol and water (95:5) as mobile phase, with a flow of 1.0 mL/minute, isocratic elution, reversed phase, column RP-18 - 250 x 4.6mm (5 µm), length of wave of 225 nm and temperature of 25°C. The analytical method is linear in the working range from 0.08 to 0.12 mg/mL, selective, sensitive, precise, accurate and robust. The forced degradation study was carried out under different stress conditions: acid, alkaline and neutral hydrolysis; to 3% hydrogen peroxide; to UV light (254 and 365 nm), to natural light and at a temperature of 60ºC. Ketoconazole will be stable to varying exposure, except for oxidation exposure, UV light exposure and natural light exposure, under exposure conditions at its content. In the quality tests, identification, pH, density and content tests were carried out in the periods of zero (after opening the bottle), 30, 60 and 90 days. For the stability test, the samples were stored in simulated conditions of temperatures 40±2ºC and relative humidity of 75%±5% for 90 days and evaluated in relation to organoleptic characteristics, density, pH, and content. In stability studies, the ketoconazole content presented in the range of 89.76 to 121.04%, resulting in non-compliance with the Brazilian Pharmacopoeia (2019). The suspension viscosity values were slightly higher than those of the vehicles. The concentration of the drug in the suspension had little influence on the viscosity of the formulation. Analysis of the reflection by microscopy it was possible to observe the heterogeneity of the particles, followed by morphological changes of the crystals. The change of thermal suspension did not present in the organoleptic characteristics, pH and density of the study. The formulation presented a sediment volume of 48% after 48 hours and a redispersion time of 1 minute and 44 seconds. The product batch developed does not present an adequate homogeneous quality of drug content.
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Palavras-chave
Estabilidade , Cetoconazol , Cromatografia , Validação , Suspensão oftálmica