Vibrational spectroscopy and chemometrics to characterize and quantitate trehalose crystallization

Investigating the phase behavior of sugars in ice and lyophilized solids is of significant interest in the pharmaceutical industry. In this study, Raman and near infrared (NIR) spectroscopy are used to characterize and quantitate trehalose crystallization using several chemometric models. The predictive behaviors of partial least squares (PLS), principal component analysis (PCA), and multiple linear regression (MLR) models are compared. In general, PLS and PCA outperform linear and MLR models. Changes in specific vibrational modes associated with several coupled motions are described and assigned as a function of crystal content. In addition to characterization and quantitation, our method may be used to localize gradients of amorphous and/or crystallized trehalose within a sample.