Cristaliza??o do princ?pio ativo farmac?utico glibenclamida por processo de precipita??o com antissolvente l?quido

• Autor(a) principal: Costa, Camila Stefanne Dias
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
• Texto Completo: https://tede.ufrrj.br/jspui/handle/jspui/2779
• topic: glibenclamida; precipita??o com antissolvente; caracteriza??o; taxa de dissolu??o; glibenclamide; antisolvent precipitation; characterization; dissolution rate; Engenharia Qu?mica

Diabetes mellitus (DM) is a chronic disease characterized by persistent hyperglycemia resulting from insulin resistance and/or deficiency. It is a metabolic disorder with high healthcare impact worldwide because of its chronic complications and high mortality rate. Type II diabetic patients can control their glycemic levels with the use of hypoglycemic drugs. Glibenclamide is a potent oral hypoglycemic drug that has been used in the treatment of DM-II, however, it has low water solubility and slow dissolution rate. In this study, glibenclamide microparticles were produced by the antisolvent precipitation process using water as the antisolvent. The four-factor three-level orthogonal array design OA9(3)4 proposed by Genichi Taguchi was used to investigate the effect of the following four factors on particle size and morphology: glibenclamide solution concentration [mg.mL-1], antisolvent/solvent volume ratio [A/S], stirring intensity [rpm], and surfactant concentration [% wt/wt]. Crystallized glibenclamide particles were characterized by optical microscopy, X-ray diffraction, and Fourier Transform Infrared Spectroscopy; the dissolution rate was characterized by HPLC. The surfactant concentration had a significant effect on the mean particle diameters of crystallized glibenclamide, followed by drug solution concentration, antisolvent/solvent volume ratio and stirring intensity, and the smaller sizes were observed with 1,0 mg.mL-1, A/S 10, 1500 rpm and 0,002 % wt/wt. The results indicate that crystallinity and chemical structure were not changed, however, the morphology and dissolution rate were affected by the factors. The results in this study show that the antisolvent precipitation process is effective in the preparation of microparticles of poorly water-soluble drugs. These contributions could expand the potential for new therapeutic drugs with low dissolution rates.