Investigation the inclusion complexes of valsartan with polysaccharide arabinogalactan from larch Larix sibirica and (2-hydroxypropyl)-β-cyclodextrin: preparation, characterization and physicochemical properties

Abstract

Valsartan is an efficacious blood pressure-lowering active pharmaceutical ingredient with highly selective antagonist of angiotensin II (type 1-receptor subtype). However, its pharmaceutical application is limited by the low oral bioavailability (~23 %), which is resulted from hydrophobic nature and poor aqueous solubility. In this study, two inclusion complexes of valsartan has been environmental-friendly synthesized using VM-1 roll mill to improve the poor oral bioavailability of valsartan by increasing its water solubility. Polysaccharide arabinogalactan from larch Larix sibirica (AG) and (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) were separately used as branched or truncated-cone inclusion carriers for valsartan. The synthesized complexes were characterized by NMR relaxation technique, DSC and powder X-ray diffraction pattern. Results showed a shorten T2 relaxation time, disappearance of valsartan endothermic peak and significant variations in X-ray pattern, indicating the formation of complexes being inclusion. In further study, physicochemical properties of valsartan and its mechanical treated complexes were investigated both in aqueous solutions and in solid state. It was found both of the two inclusion complexes successfully improved the solubility of valsartan (Valsartan/AG inclusion complex increased from 0.24 to 0.42 g L−1; Valsartan/HP-β-CD inclusion complex increased from 0.24 to 0.82 g L−1, +37 °C). On the other hand, the rapid storage test showed the inclusion formation of valsartan kept a similar stability as its pure form (+40 °C for 2 months). Taking into account of above results, it is concluded the two synthesized inclusion complexes are promising to improve the bioavailability of valsartan with a better solubility and without changing its stability.