Enhancement of Ticagrelor solubility by comparative study of solid dispersion techniques: Hot melt extrusion and solvent evaporation

Abstract

Ticagrelor (TCG) is a BCS Class IV antiplatelet agent that exhibits low aqueous solubility and poor intestinal permeability, both of which significantly limit its oral bioavailability. In an effort to overcome these biopharmaceutical challenges, the present research aimed to enhance the solubility and dissolution behavior of TCG through the solid dispersion (SD) technique. Five different polymers Kollidon® VA64, Kollidon® K17, Kollidon® K30, Soluplus®, and PEG 6000—were selected based on their solubilizing potential and process compatibility. Solid dispersions were prepared using two widely employed methods: solvent evaporation and hot-melt extrusion (HME). The prepared SDs were subjected to comprehensive characterization to assess drug-polymer interactions, physical state, and in vitro dissolution performance. Among all tested combinations, the formulation based on Kollidon® VA64 prepared by HME demonstrated the most significant improvement in solubility and dissolution rate compared to the pure drug and physical mixtures. This optimized solid dispersion was further processed into immediate- release (IR) tablets using the direct compression method. Physicochemical analyses such as Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) confirmed the successful conversion of the drug to an amorphous state and the absence of any incompatibility with selected excipients.The study highlights the effectiveness of Kollidon® VA64 as a carrier and the advantages of the HME technique in improving drug release. The developed IR formulation presents a promising strategy for enhancing the oral bioavailability and therapeutic potential of Ticagrelor.