Investigation of the dissolution rate and oral bioavailability of atenolol-irbesartan co-amorphous systems

Abstract

Irbesartan (IBS), a common drug to treat hypertension, has poor oral bioavailability because of its limited aqueous solubility. Recently, co-amorphous systems (CAMs) have demonstrated the ability to improve the solubility of poorly water-soluble drugs. In this study, IBS was co-amorphized with a pharmacologically relevant drug atenolol (ATL) by melt-quenching. The structures of the resulting ATL-IBS CAMs, which were formulated in molar ratios of 2:1, 1:1, 1:2 and 1:4, were characterized by the polarizing microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier-infrared transform spectroscopy. ATL-IBS CAM_1:1 showed higher IBS dissolution than crystalline IBS, amorphous IBS (IBS AM) and the other CAMs. The results of the supersaturated solution stability showed that ATL enhanced the supersaturation maintenance of IBS by extensive interactions. The CAMs exhibited excellent physical stability at 25°C/60% RH. The pharmacokinetics experiments showed that the relative oral bioavailability of IBS was 2.78-fold higher than bulk IBS (p < 0.001) after oral administration of ATL-IBS CAM_1:1 to rats. The results of this study demonstrate that CAMs provide an alternative option for the development of fixed dose combination of ATL and IBS.