Polymorphism in precipitation processes

Abstract

Polymorphism is the phenomenon that molecules of a compound are able to form more than one crystal structure. These structures possess different properties that are of considerable interest to industry, for example, the solubility and hence bio-availability of pharmaceuticals. Only one of the polymorphic structures is thermodynamically stable but the formation of a metastable structure may be kinetically favoured eventually followed by transformation to the stable structure. To relieve the high supersaturation that is generally created in precipitation processes molecules may follow different polymorphic pathways for nucleation and growth. Apart from the formation of a metastable crystalline phase evidence is presented that also a highly metastable liquid-liquid separation may occur. Control over the formation of polymorphs therefore requires control over their relative nucleation rates. This research offers guidelines to achieve control over the polymorphic pathways in precipitation processes.