Effects of seed quantity and property on selective crystallization of pharmaceutical compounds

IEC 74

Jian Wang, Jennifer Baxter, Aaron Cote, Nausheen Khokhar, John Lepore, Christopher Loose, Amar Mahajan, Richard Osifchin, and Mary Stanik. Chemical Engineering R&D Department, Merck & Co., Inc, P.O. Box 2000, RY818-C312, Rahway, NJ 07065
Crystallization is a primary purification/isolation method for production of active pharmaceutical ingredients (APIs). The API products often must possess reproducible high chemical purity and specific physical properties, e.g., crystal form, morphology and crystal size distribution. Although seeding is well recognized as a critical contributor to the control of crystallization processes, the effects of seed quantity and physical properties on selective crystal growth often are under-evaluated or not fully utilized in the development, design and optimization of crystallization processes. This paper will present results from studies on crystallization of Merck APIs exploding the role of seed quantity and properties in selective growth of desired crystals. The results demonstrate the impacts of seed quantity and characteristics on (1) controlled isolation of target crystal form, (2) minimization of solvent occlusion, (3) control of crystal size, and (4) robustness of process scale-up, in relation to the crystal growth and/or nucleation kinetics during the crystallization.