Solubility Enhancement of Ticagrelor by Different Complexation Methods

Abstract

The antiplatelet medication ticagrelor is taken orally and found as a crystalline powder with a water solubility of approximately 3.5μg/ml at room temperature. Within the physiological range, ticagrelor has no pKa value. The Biopharmaceutics Categorization defines ticagrelor as a "poor solubility, low permeability medication" because it lacks pH-dependent solubility (Class IV). The average unmodified bioavailability of ticagrelor in healthful volunteers is 36%.

The research seeks to enhance the solubility and dissolution of ticagrelor by utilizing various methods. It aims to prepare the cyclodextrin inclusion complex.

Physical trituration, kneading, and solvent evaporation were all employed to create nine formulas of cyclodextrin inclusion complex with HPβCD. Saturated solubility, FTIR, and DSC were used to characterize the produced formulations.

In terms of the ticagrelor inclusion complex with hydroxyl propyl beta cyclodextrin (HPβCD). All complexes enhanced solubility by forming an inclusion complex with HPβCD. However, the solvent evaporation process proved the most effective for ticagrelorsolubilization. The optimum inclusion complex formula (F9) demonstrated a tenfold increase in saturated solubility over the pure drug.