Particle size distribution control of active pharmaceutical ingredients is an important factor when developing a direct compression solid oral formulation. A variety of common methods exist for particle size control including controlled reactive, thermal, and anti-solvent crystallizations, as well as mechanical size reduction techniques such as milling.
This work demonstrates the utility of a multi-step recrystallization to control particle growth and final size distribution. A seeded, thermal, and anti-solvent recrystallization for particle size control will be presented, as well as the challenges associated with scaling up this complex process. These challenges can be understood through well-designed scaled-down experiments to map how process parameters impact material attributes.
