Controlled anti-solvent precipitation for enhanced dissolution rate and antiplatelet activity of ticagrelor

The goal of our study is to augment ticagrelor (TC)'s dissolution rate and antiplatelet activity via controlled antisolvent precipitation. A saturated ethanolic solution of TC was prepared in the absence and presence of poloxamer 188 or gelucire 44/14. Aerosil 200 was added before controlled precipitation using water or water-containing poloxamer (1% w/v). The resulting precipitate was dried and characterized using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and in vitro dissolution. FTIR showed hydrogen bonding after the processing of TC. DSC and PXRD reflected partial amorphization. A significant enhancement (p < 0.05) in dissolution efficiency and TC amount released after five minutes was also shown. The most effective composition was F6, which comprised TC, poloxamer, and Aerosil (5:5:2.5), or F9, utilizing gelucire instead of poloxamer at a similar ratio. Assessment of tail bleeding time (min) exhibited a significant (p < 0.05) prolongation for rat groups treated with F6 (24.71 ± 5.46) and F9 (30.06 ± 1.63) compared with negative control (3.43 ± 0.46) and unprocessed TC (5.78 ± 2.18). These results suggest an enhancement of TC's pharmacological activity probably due to enhanced bioavailability imparted with an enhanced dissolution rate. The study introduced controlled antisolvent precipitation as a simple tool for hastened TC's dissolution.