Exploring the utility of co-amorphous materials to concurrently improve the solubility and permeability of Fexofenadine

Abstract

In this study, the co-amorphous materials of BCS class-IV drug Fexofenadine were prepared by employing Naringin as a co-former. Naringin was employed as a coformer anticipating the concurrent improvement in the solubility and permeability by virtue of its good glass-forming ability and p-gp inhibition potential, respectively. The solid-state characterization of prepared co-amorphous materials by powder-XRD, DSC, and FTIR revealed amorphous state and π-π interactions between Fexofenadine and Naringin. The interactions were confirmed by Molecular Dynamic studies employing Schrodinger material science Suite®. The co-amorphous materials demonstrated improved solubility and dissolution for both Fexofenadine and Naringin. The deliquescent nature of Naringin led to the significant moisture uptake by coamorphous materials. However, the dissolution advantage of Fexofenadine and Naringin sustained in the stability samples due to accelerated π-π interactions in the presence of water. The permeability of co-amorphous samples was estimated using everted gut sac method which was found improved by 5-fold and 3.5-fold for Fexofenadine and Naringin, respectively. The improvement in the permeability was attributed to the interplay between solubility improvement and dose-dependent P-gp inhibition by Naringin.