Estudo de dissolução de arteméter e lumefantrina em comprimidos de dose fixa combinada para avaliação de correlação in vitro-in vivo

• Ano de defesa: 2016
• Autor(a) principal: Graziella Gomes Rivelli
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Solubilidade em equilíbrio; Correlação in vitro-in vivo; Lumefantrina; Classificação biofarmacêutica; Dissolução; Arteméter; Química farmacêutica; Malária; Arteméder; Comprimidos Dissolução; Antimaláricos
• Link de acesso: http://hdl.handle.net/1843/BUOS-B4XMEN

Nowadays, malaria is the most incident parasite infection worldwide. Artemisinin based combination therapy (ACT) has been proposed as a promising treatment for malaria, and artemether+lumefantrine (20 + 120 mg) is the main recommended association in endemic areas. Despite its widespread use, there is still incipient literature for dissolution of artemether and lumefantrine, reflecting in absence of specific method in pharmacopoeias and international codes. Because its low solubility, both artemether and lumefantrine are candidates for development of dissolution methods using in vitro-in vivo correlation (IVIVC). In this study, dissolution methods for artemether and lumefantrine were developed and validated according to ANVISA and FDA guidelines. Dissolution profiles were performed, evaluating the results obtained with alternate changes of test parameters such as medium composition, pH, surfactant concentration and rotation speed. Experiments were conducted using the same batch of Coartem evaluated in a previous pharmacokinetic study, and in vivo data were used to select the optimum conditions for dissolution test, based on IVIVC. For drugs quantitation, a selective method by high performance liquid chromatography was optimized and validated. For this formulation, the best conditions found for artemether were: paddle, 900 mL of dissolution medium containing pH 6.8 buffer with 1% sodium lauryl sulfate and rotation speed of 100 rpm. For lumefantrine, the best conditions were: paddle, 900 ml of dissolution medium containing pH 1.2 buffer with 1% polysorbate 80 and rotation speed of 100 rpm. After obtaining the curve of absorbed fraction due to dissolved fraction, the calculated slope values were above 0.95 for both drugs. Thus, methods and criteria were established for testing dissolution of artemether and lumefantrine tablets and consequently, for the elaboration of monograph for Brazilian Pharmacopoeia.