Physicochemical characterization and in vivo assessment of novel apixaban-loaded polymeric nano-aggregates

The objective of this study was to enhance the aqueous solubility and oral bioavailability of nearly water-insoluble apixaban (APX) using polymeric nano-aggregates (PNAg), a modified drug delivery system.

Various APX-PNAg samples were prepared through solvent evaporation using a spray dryer, and their solubility and dissolution were compared with those of APX powder. Moreover, solid-state characterization, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM), of APX-PNAgs was performed and compared with that of the drug powder and physical mixture. Additionally, a pharmacokinetic study of APX-PNAg was performed in Sprague-Dawley rats and compared with that of APX powder.

The formulation consisting of APX and hydroxypropyl β-cyclodextrin (HP-β-CD) at the weight ratio of 1:10 was chosen owing to its highest solubility and dissolution rate. The selected formulation produced fine spherical aggregates, with the drug altered to an amorphous state. The DSC analysis demonstrated the thermal stability of APX-PNAg. Moreover, the optimized APX-PNAgs showed significantly (77 times) improved solubility and 4.8-times augmented bioavailability when combined with pure APX.

PNAg may significantly enhance the solubility, dissolution, and oral bioavailability of poorly water-soluble drugs.