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Updated: Apr 28, 2026

Optimization of Crystal Growth for Neutron Macromolecular Crystallography
Published on: March 13, 2021
Crystal engineering for poorly water-soluble drugs: From design to applications
An Chen1, Yayun Peng1, Zhuangzhuang Chen1
1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing 211198, China.
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The limited aqueous solubility of active pharmaceutical ingredients (APIs) remains a major challenge in drug development, severely compromising clinical performance. Crystal engineering has emerged as a powerful and versatile approach to address this issue by rationally designing API crystal structures through precise control of intermolecular interactions, thereby enhancing solubility, dissolution rates, and ultimately bioavailability. This review systematically summarizes recent advances in crystal engineering strategies for poorly water-soluble drugs, including polymorphs, cocrystals, solvates/hydrates, nanocrystals, organic framework solids, solid solutions, liquid crystals, amorphous solids, and salts. Additionally, key challenges in translational applications are discussed, including structure-property relationship, AI-driven computational modeling, in vitro-in vivo correlation establishment, and advanced crystallization techniques. The review aims to provide strategic insights of crystal engineering for overcoming solubility barriers in next-generation drug formulations.
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