Belov Konstantin V, Khodov Ilya A
G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo 153045, Russia.
Molecules. 2025 Sep 18;30(18):3793. doi: 10.3390/molecules30183793.
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.
比卡鲁胺（BCL）是一种临床上重要的非甾体抗雄激素药物，具有显著的构象多态性和复杂的固态行为，这对其物理化学和生物制药性质有着至关重要的影响。本综述全面整合了当前关于BCL的结构特征、多晶型形式和分子间稳定机制的计算和实验研究结果。从多晶型稳定性、溶解度和溶解动力学方面考察了包括扭转灵活性、氢键网络、π-π堆积和氟-氟接触等关键因素。该综述还综合了固态优化策略（包括共晶体、溶剂化物、无定形形式和固体分散体）的最新进展，并探讨了超临界流体（SCF）技术在颗粒工程和溶出度提高方面的新作用。这项工作通过将分子层面的认识与制剂方法联系起来，为设计具有更高生物利用度和稳定性的下一代BCL固体形式提供了一个框架。
