Concept of Spherical Crystallization

Abstract

In this Chapter we describe how the concept of “spherical crystallization” was found based on the findings by Stock that ultrafine particles of barium sulfate can be spherically self-organized as an agglomerate in benzene under stirring. It was shown that the spherical agglomerate was not formed in absolutely dried benzene, suggesting that a small amount of water is required to preferentially wet the particles for self-organized agglomeration. Firstly, we found that antisolvent-crystallized salicylic acid is spherically self-agglomerated together with a small amount of bridging liquid, which is liberated by phase separation from the crystallization system, a good solvent–anti-solvent–bridging-liquid mixed system, under stirring. The resulting agglomerated crystals show paradigm shifted micromeritic properties such as free flowing and binder-free direct tabletability. An important factor determining the spherical crystallization behavior and micromeritic properties of the system was found to be its ethanol fraction rate. It was also found that spherical crystallization processes involving the diffusion-controlled crystallization and agglomeration of crystals occurred simultaneously before finishing the crystallization, and that a continued coalescence of crystals took place even after the process had finished.