ABSTRACT:
Ticagrelor is an orally active P2Y12 receptor antagonist used in the management of acute coronary syndrome, but its oral performance is limited by poor aqueous solubility and variable dissolution behavior. The present study aimed to develop ticagrelor solid dispersion tablets using hydrophilic carriers in order to improve wettability, reduce crystallinity and enhance drug release. Solid dispersions were prepared by the solvent evaporation approach using PVP K30, PEG 6000 and HPMC E5, followed by direct compression into 300 mg tablets. Nine formulations (F1-F9) were prepared by varying PVP K30 and PEG 6000 concentrations while maintaining a ticagrelor dose of 60 mg. Preformulation studies confirmed that ticagrelor was a white to off-white crystalline powder with poor aqueous solubility, a melting point of 144.75 °C and a UV absorption maximum at 255 nm in methanol. The calibration curve was linear over 2-10 µg/mL with a regression equation of A = 0.0614C - 0.0186 and R² = 0.9959. FTIR spectra retained characteristic bands of ticagrelor, while DSC showed a slight broadening/shift of the melting endotherm in the physical mixture, suggesting compatibility with selected excipients. Prepared powder blends showed acceptable flow with Carr’s index of 11.53-17.64% and Hausner ratio of 1.13-1.21. Tablets complied with quality parameters for weight variation, friability (<1%) and drug content (96.4-99.4%). Batch F6, containing ticagrelor:PVP K30:PEG 6000 at 60:60:60 mg, was optimized because it showed the best overall profile, including excellent flow, highest hardness (3.2 kg/cm²), lowest friability (0.41%), acceptable disintegration (45 min), highest drug content (99.4%) and maximum final drug release (83%). Accelerated stability testing for three months showed no visible change and only a slight decrease in drug content and release. The study indicates that solid dispersion using PVP K30 and PEG 6000 is a simple and practical approach to improve the dissolution performance of ticagrelor tablets.