Optimizing Particle Properties For Difficult Small Molecules: Solid-State Strategies For Improved Manufacturability

Crystallization is usually treated as an isolation step, yet it also shapes the material attributes that determine whether a small molecule API can be filtered, dried, and handled at scale. Three development problems show where conventional optimization stalled. In one, the thermodynamically preferred polymorph formed a dense needle felt that solvent and seeding changes could not fix. In another, a narrow metastable zone ruled out seeded cooling crystallization. In the third, fine particles slowed filtration and hardened into golf ball-like agglomerates during drying. Authors Bertram Cezanne (Process Development) and Axel Becker (Lab Services) describe how each problem was diagnosed and what the solutions suggest about designing particles on purpose.

Delve into the cases to see what the team found.