PREPARATION AND CHARACTERIZATION OF COAMORPHOUS GLIBENCLAMIDE SYSTEM

STERREN, V; ZOPPI, A; ABRAHAM MIRANDA, J; LONGHI, MR

Córdoba (Córdoba)

Congreso; 3° Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2014

Glibenclamide (GLB) is an oral hypoglycemic agent used in the treatment of type II diabetes. GLB belongs to class II compound according to the biopharmaceutics classification system due to its low aqueous solubility. Coamorphous drug arrangements were recently introduced as potential drug delivery systems for poorly water soluble drugs. In this approach, an active pharmaceutical ingredient and small molecular weight excipients are chosen and combined in order to prepare coamorphous mixtures with improved dissolution properties. Based on these above considerations, the present investigation was aimed to develop and characterize GLB coamorphous mixtures with arginine (ARG) to improve the drug dissolution characteristics. X-ray powder diffractometry, infrared spectrometry (IR) and confocal laser scanning microscopy (CLSM) were used to investigate the physicochemical characteristics of the solids. The comparative dissolution behavior of the newly developed solid form and that of the untreated GLB were also studied, for which the prepared sample and the raw drug were added to 500 ml of pH 7.4 phosphate buffer, at a temperature of 37.0 ± 0.5 °C and paddle-stirred at a rotation speed of 50 rpm. The diffractogram of GLB/ARG system was distinguishable from GLB and ARG raw materials, and showed the absence of sharp diffraction peaks, indicating the formation of a coamorphous solid. The CLSM analysis confirmed the differences in the particles morphology between GLB/ARG system and the raw materials. IR spectra showed molecular differences between the coamorphous system and the untreated drug. Furthermore, it could be shown that the dissolution rate of GLB/ARG in pH 7.4 phosphate buffer was faster than that of the crystalline pure drug. Therefore, it can be concluded that the amorphous form of GLB and ARG produced in this study has shown promising results in vitro, and is a candidate for further studies aimed at improving the bioavailability of GLB.