To Study the Impact of Ultrasound-Assisted Antisolvent Crystallization on Aprepitant Crystal Habits

Aprepitant (APT), an antiemetic drug used for chemotherapy-induced nausea and vomiting (CINV), exhibits poor compressibility, solubility, and micromeritic properties. Crystal habit modification was studied using solvent evaporation, conventional antisolvent crystallization (APT_AS), cooling crystallization (APT_CC), and the advanced sonocrystallization technique (APT_SN). Morphological analysis of the sonocrystallized crystals revealed small, platy crystals exhibiting an aspect ratio of 1.35 ± 0.04 and a span value of 1.06. The APT_SN showed improved micromeritics as compared to APT_AS (1.59 ± 0.03) and APT_CC (1.48 ± 0.04) (antisolvent-crystallized APT and cooling crystallized APT, respectively). All modified crystals exhibited a plate-shaped crystal habit with no agglomeration. The angle of repose, Carr’s index, and Hausner’s ratio exhibit that the APT_SN showed improvement in powder properties. Solid-state characterization using differential scanning calorimetry (DSC), Powder X-ray Diffraction Spectroscopy (PXRD), and Thermogravimetric Analysis (TGA) proved no change in polymorph. Contact angle-driven wettability was as follows: APT > APT_AS > APT_SN > APT_CC, and the results were corroborated by X-ray photon spectroscopy (XPS) and intrinsic dissolution profiles. The XPS studies revealed a decrease in the surface polar component of APT_SN, resulting in reduced wettability. APT_SN showed the highest tensile strength at 20 kg/cm2 among all other crystals. All the modified crystals exhibited a reduced IDR profile, resulting from a reduction in the polar component at the surface.