Monitoring of Crystalline Transition During Wet Granulation Process Using Probe Type Low-frequency Raman Spectrometer:(TJPS-2020-0060.R1)

Abstract

Recent years, real time analysis has been widely studied using various Process Analytical Technology tools particularly in the quality control of drug products. In this study, we investigated the improvement of sensitivity and the reduction of measurement time by using a low frequency (LF) Raman spectrometer equipped with a new light source for in situ monitoring of crystalline transformation of active pharmaceutical ingredients (API) during wet granulation process. Three model drugs were chosen to assess the system sensitivity, hydrate transition and cocrystal dissociation. LF Raman spectra showed the specific peaks for crystalline indomethacin and theophylline which were typical and well known for Raman active APIs. The laser power was strengthened from 58 to 300 mW, thus the measurement time can be reduced nearly five hundred times which was significantly faster than the old probe. In addition, signal to noise ratio was drastically improved as seen from the clear signal intensity of API with low interference from the excipients. Obvious peak shifts were observed in the spectra of LF region reflecting the dissociation of CAF cocrystal. These three model drugs suggested that LF Raman spectroscopy is preferable for specific detection of crystalline APIs.

:TJPS-2020-0060.R1