Fabrication of an aprepitant nanosuspension using hydroxypropyl chitosan to increase the bioavailability.

Aprepitant has been classified into BCS class IV, which has low permeability and poor water solubility, resulting in low bioavailability. This study focused on improving its permeability and solubility in order to improve the oral bioavailability of aprepitant. Hydroxypropyl chitosan (HPCS) was used as a stabilizer for the nanosuspension and wet milling was utilized for improving aprepitant's bioavailability and solubility. The resulting nanosuspension size was 151 ± 14.5 nm and its zeta potential was 63.5 ± 0.34 Mv. The spectral characteristics (XRPD, DSC, TEM) of the nanosuspension suggested that aprepitant existed in the crystalline form and that nanosuspension had 2-fold higher solubility than aprepitant. Hydroxypropyl chitosan can significantly reduce the TEER of Caco-2 cells and the Papp of the suspension in Caco-2 cells increased by 2.2 times compared with aprepitant. The relative bioavailability of the nanosuspension was 147.7% compared with the commercial capsule.

Preparation and Characterization of Aprepitant Solid Dispersion with HPMCAS-LF.

This study focused on improving the physicochemical characteristics of aprepitant with poor water solubility by preparing solid dispersion (SD). To prepare the SD with HPMCAS-LF, the solvent evaporation method was applied. Based on dissolution analysis, the dissolution rate of SD increased by five times compared with aprepitant. In addition, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) results suggested the presence of amorphous-form aprepitant inside SD. According to Fourier transform infrared (FTIR) spectroscopy, intermolecular hydrogen bonds were detected between polymer and aprepitant. The Caco-2 cell experiment proved that SD did not lower the transepithelial electrical resistance (TEER) values but improved the permeation amount of aprepitant. Additionally, the SD of aprepitant displayed excellent stability.