Study of the Preparation of Amorphous Itraconazole Formulations

Abstract

The formulation of poorly water-soluble active pharmaceutical ingredients (APIs) has been widely studied in the last few decades to overcome the limited bioavailability imposed by these pharmaceutical ingredients. In this work, supercritical fluid extraction of emulsions has been applied using two different types of excipients, i.e., poly(vinyl alcohol) (PVA) and glycyrrhizic acid (GA), to address the precipitation of itraconazole (ITZ) as an amorphous solid. The delivery profiles of the in vitro dissolution tests of the ITZ–GA particles confirmed the advantage of the manufactured amorphous material in terms of apparent solubility in comparison to the raw ITZ. Furthermore, the stability of an amorphous glassy product and its potential to recrystallize in the presence of water have been experimentally determined using both excipients and interpreted applying molecular dynamics (MD) simulations. Results show that recrystallization of the amorphous ITZ particles starts at their surface, corroborating that th...