Utilizing phospholipid as an amphiphilic carrier for solid dispersion of ambrisentan: formulation and evaluation

Abstract

ABSTRACT: The partial water solubility of ambrisentan poses a challenge to its oral administration despite being the second oral endothelin A-receptor antagonist approved in the United States. In this study, we aimed to improve ambrisentan’s solubility and bioavailability using an amphiphilic phospholipid carrier. Phospholipids, with their glycerol-bound, phosphorus-containing amphiphilic nature, are known to prolong drug lifespan by facilitating drug penetration across cell membranes through hydrogen bonds or van der Waals interactions. Moreover, phospholipid compounds have been shown to significantly enhance drug solubility, permeability, and bioavailability in various studies. We optimized the ratios of ambrisentan and phospholipid carriers (1:1, 1:3, and 1:5) based on saturation and phase solubility experiments. Solid dispersion was prepared using the solvent evaporation technique. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses confirmed the conversion of ambrisentan from a crystalline to an amorphous form in the solid dispersion. The solubility of ambrisentan in the solid dispersion increased by 13-fold with a 1:5 ratio of ambrisentan to phospholipid carrier. The release profile indicated rapid release of the active substance within the first 15 min, corresponding to the peak phospholipid concentration. Pharmacokinetic studies demonstrated higher bioavailability of the medicine compared to the pure drug. This study suggests that phospholipids can effectively enhance drug solubility and bioavailability in solid dispersion systems.