Amorphization of Ticagrelor Through Preparation with Cyclodextrins – Solid State Characterization

Background: /Objectives: Approximately 90% of newly developed active pharmaceutical ingre-dients (APIs) exhibit low solubility in aqueous environments. The formation of cyclodextrin (CD)-guest inclusion complexes (ICs) is one method of increasing the solubility of poorly soluble drugs. In contrast to its crystalline state, a compound is more soluble in its amorphous solid state. Methods: The purpose of this work was to investigate how the solid-state characteristics of ti-cagrelor (TICA) are affected by complexation with specific cyclodextrins. TICA inclusion com-plexes containing three different types of CDs were prepared by freeze-drying, co-precipitation, and kneading methods. Solid-state characterization of pure ingredients, physical mixtures (PMs) and TICA-CD ICs was performed using: scanning electron microscopy (SEM), powder X-ray diffraction analysis (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and temperature-modulated differential scanning calorimetry (TMDSC). Results: The freeze-drying method was the most effective in terms of obtaining TICA in the amorphous state. Using the kneading technique, the complexes with lower crystallinity were obtained compared to pure ticagrelor. Since almost pure crystalline ticagrelor was found in the mixes produced by co-precipitation, it may be said that the procedure was unsuccessful. Conclusions: Therefore, our findings suggest that kneading and, particularly, freeze-drying techniques are useful approaches for preparing TICA–CD amorphous ICs.