Quantitative in-line monitoring of solvent-mediated polymorphic transformation of sulfamerazine by near-infrared spectroscopy.

ABSTRACT: The in-line monitoring of pharmaceutical processes with high risk, such as crystallization, has been one of the most popular research topics in recent years. Sulfamerazine (SMZ), a well-known sulfonamide antibacterial agent was investigated to examine the mechanism of polymorphic conversion by solvent-mediated polymorphic transformation (SMPT). The primary purpose of this study is to monitor the polymorphic transformation through in-line near-infrared (NIR) measurements and concurrently interpret the whole process quantitatively with off-line characterizations. Samples taken at every hour during SMPT were analyzed by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). NIR spectra in the range of 7500–4900 cm −1 were taken into account for multivariate analysis, which included partial least square (PLS) regression and principal component analysis (PCA). In brief, the form II content was estimated very accurately and reproducibly during the SMPT process not only by XRD but also by the DSC measurements. In addition, the form II content values were predicted very accurately by separate experiments at two designated time points. In a separate study, it was demonstrated that PCA could be employed to explain a complicated process such as SMPT mechanistically by several stages