PREPARATION OF MULTICOMPONENT CRYSTAL TICAGRELOR-MEGLUMINE AND ITS PHYSICOCHEMICAL CHARACTERIZATION

Abstract

Objective: Ticagrelor (TICA), an antiplatelet agent used in cardiovascular treatment, is classified as a Class IV compound in the Biopharmaceutical Classification System, characterized by low solubility and low permeability, leading to poor bioavailability. This study aimed to enhance the solubility and dissolution rate of TICA through the formation of a multicomponent crystal with meglumine. Methods: Multicomponent crystals were prepared using the solvent drop grinding method. A binary phase diagram of ticagrelor and Meglumine (MEG) was constructed to determine the eutectic composition and temperature. Characterization was conducted using Differential Scanning Calorimetry, Fourier Transform Infrared Spectroscopy, Powder X-ray diffraction, and Scanning Electron Microscopy. Solubility tests and in vitro dissolution studies were performed to evaluate improvements in solubility and dissolution rate. Results: The binary phase diagram confirmed a simple eutectic mixture at a 4:6 molar ratio, with a eutectic temperature of 124.31 °C. The multicomponent crystal demonstrated 1.4 times higher solubility compared to intact ticagrelor. Dissolution studies showed significant improvements: 70.44% in 0.1 N HCl and 62.27% in CO₂-free distilled water within 60 min, compared to 40.39% and 31.38%, respectively, for intact TICA (P<0.05). Conclusion: The formation of TICA and MEG multicomponent crystals significantly enhanced solubility and dissolution rates, suggesting its potential to improve the bioavailability of TICA. This approach highlights the promise of multicomponent crystal technology in addressing the bioavailability challenges of Class IV drugs.