Conformational Landscape, Polymorphism, and Solid Forms Design of Bicalutamide: A Review

Bicalutamide (BCL), a clinically important non-steroidal antiandrogen, exhibits pronounced conformational polymorphism and complex solid-state behaviour that critically influence its physicochemical and biopharmaceutical properties. This review comprehensively integrates current computational and experimental findings on the structural features, polymorphic forms, and intermolecular stabilisation mechanisms of BCL. Key factors, including torsional flexibility, hydrogen-bond networks, π-π stacking, and fluorine-fluorine contacts, are examined with respect to polymorph stability, solubility, and dissolution kinetics. The review also synthesises recent advances in solid-state optimisation strategies-including co-crystals, solvates, amorphous forms, and solid dispersions-and explores the emerging role of supercritical fluid (SCF) technologies in particle engineering and dissolution enhancement. This work offers a framework for designing next-generation BCL solid forms with enhanced bioavailability and stability by connecting molecular insights with formulation approaches.