Crystallization

Crystallization is a ubiquitous process involving the formation of solid crystals.  Crystal formation may occur via a number of processes, including cooling and evaporation, under a variety of conditions. A critical unit operation in pharmaceutical active ingredient production is crystallization.  During this process, API's undergo crystal engineering in order to assure that the final desired crystalling form is produced.

Raman spectroscopy is a praticularly effective tool for the characterization of different types of crystalline forms of the same material (polymorphic forms).  The reason is that the moecules in crystalline materials are, by definition, ordered in a specific manner.  As a results, the Raman spectra of crystalline materials give rise to very sharp and intense bands.  In addition a chemical moiety in one crystalline form may exist in a different environment from the same moiety in another form leading to band shifts.  These band shifts can be characteristic of one polymorphic form and be used to qualitatively identify and quantitatively measure the polymorphic composition.

Raman spectroscopy has become an established tool in monitoring crystallization phenomena as it can be used in development to understand a process and then transition with the chemistry through scale-up and into manufacturing.  In manufacturing Raman can be used to:

1. Monitor the Progress of the Crystallization Process
2. Assess the Endpoint
3. Assure that the Correct Polymorph has been Formed.
 

The ability to characterize, optimize, and control the crystallization process, polymorphic forms and co-crystals are thus industrially critical. Raman spectroscopy enables in situ, non-destructive and fast quantitative measurements to meet these needs as well as offering the ability to analyze forms non-destructively in a manner that is scalable from Discovery to Manufacturing.

Contact a Kaiser Expert to discuss your applications needs.
 

Further information on Raman applications can be found in Handbook of Raman Spectroscopy:  From Laboratory to Process Line by Ian R. Lewis and Howell G. M. Edwards, Marcel Dekker, New York, New York (2001) and Pharmaceutical Applications of Raman Spectroscopy by Sobodan Sasic, John Wiley and Sons, Hoboken, New Jersey (2008)

 

Application Resources
Title
Category
Format
ID#
 
In Situ Crystallization Monitoring
Raman Application Note
PDF
AN301
In-line Raman Monitoring of Protein Batch Crystallization
Raman Application Note
PDF
AN325
Monitoring a Pharmaceutical Crystal Transformation In Situ
Raman Application Note
PDF
AN307
Raman-Based Endpoint Detection of a Heterogeneous Etherification Reaction
Raman Application Note
PDF
AN329
Raman-Based High-Throughput Screening for Version and Polymorph Identification
Raman Application Note
PDF
AN311
Rapid Monitoring of Antisolvent Addition Crystallization and Dehydration
Raman Application Note
PDF
AN308