METTLER TOLEDO
 

A Calibration-Free Application of Raman Spectroscopy to the Monitoring of Mannitol Crystallization and Its Polymorphic Transformation

Hongxun Hao, Weiyi Su, Mark Barrett, Vincent Caron, Anne-Marie Healy, and Brian Glennon A Calibration-Free Application of Raman Spectroscopy to the Monitoring of Mannitol Crystallization and Its Polymorphic Transformation, Org. Process Res. Dev., 2010, 14 (5), pp 1209–1214, DOI: 10.1021/op100142k

Raman spectroscopy is one of a number of potential in situ process analysis technologies (PATs) for application in crystallization processes. In this paper, the use of Raman spectroscopy in the cooling crystallization of mannitol is investigated. Mannitol has three known polymorphs (α, β, and δ) that can be assessed using Raman spectroscopy. Although several multivariate spectroscopic methods for measuring both the dissolved concentration and the polymorphic form using Raman exist, their application requires significant calibration and/or that several assumptions be made about the relationship between the concentration and the Raman spectra. In this paper, a novel and simple calibration-free univariate method for monitoring supersaturation during the cooling crystallization of mannitol is demonstrated. The use of the method to successfully monitor the transformation process of the metastable α form to the stable β form in aqueous solution is also presented.

Related Topics
: raman spectroscopy, crystallization, ATR-FTIR, FBRM, PAT, Mannitol, supersaturation