Selective Crystallization of the Metastable Anhydrate Form in the Enantiotropic Pseudo- Dimorph System of L-phenylalanine using Feedback Concentration Control

摘要

Polymorphism is described as the ability of a compound to adopt more than one crystal structure. Although chemically identical, each polymorph has its own unique combination of physical, thermal, and mechanical properties. These in turn exert an influence on the performance of the product; for example, the bioavailability and shelf-life of pharmaceutical compounds. It is therefore crucial to have a consistent and reliable production process for the specific polymorph to achieve feasible economic yield and for regulatory compliance. It is often possible to obtain the thermodynamically stable polymorph without much complication under suitable crystallization conditions such as temperature and agitation rate, for a long enough experiment. Producing large crystals of a metastable form is more challenging, the main challenge being to prevent cross nucleation of the stable form. A variation of polymorphism is the crystallization of hydrates or solvates in which solvent molecules are incorporated into the crystal structure at well-defined lattice positions; these crystalline forms are called pseudo-polymorphs.