Entry Date:
November 3, 2011

Nucleation

Principal Investigator Allan Myerson


Crystallization is vital to many processes occuring in nature and manufacturing. In chemical, pharmaceutical and food industries, crystallization from solution is widely used for a variety of materials. it is an attractive isolation step during manufacturing as particle formation and purification are combined within a single process. Almost all of the products based on fine chemicals, such as dyes, explosives and photographic materials, require crystallization in their manufacture and over 90% of all pharmaceutical products contain bioactive drug substances and excipients in the crystalline solid state. Hence it is necessary to control the crystallizaiton process in order to obtain products with desired and reproducible properties: size, purity, morphology and crystal structure. It is vital om pharmaceutical industry to produce the desired crystal form (polymorph) to assure the bioavailability and stability of the drug substance. While the target of many crystallizaiton operations is to produce crystals large enough to be isolated easily on standard filtration equipment, smaller particle sizes are desired occasionally in pharmaceuticals to enhance the dissolution rate, thus improve the bioavailability. In solution crystallization, nucleation plays a decisive role in determining the crystal structure and size distribution, therefore understanding the fundamentals of nucleation is crucial to achieve control over these properties. Classical nucleation theory is widely applied to solution crystallization due to its simplicity; however its shortcomings suggest that nucleation of solids from solution does not proceed via the classical pathway but follows much more complex routes. In the last decade, a line of studies including those reported by our group have suggested an alternative mechanism of crystal nucleation from solution called two-step mechanism.

Current work in this area includes:
(*) Electric field effects on nucleation
(*) Concomitant nucleation of polymorphs
(*) Studies of pre-nucleation solution structure