In this work the capability of portable Raman as a process monitoring tool is shown based on the use of B&W Tek’s i-Raman Plus. Measurements were performed using portable i-Raman Plus equipped with a sensitive TE-cooled back-thinned CCD as well as a patented CleanLaze® laser excited at 785 nm with 300 mW maximum power output, covering the spectral range from 175-3200 cm^-1. A long shaft lab grade Raman probe is positioned above the sample surface, at a working distance of 5 mm such that the laser is well focused as a spot. Data were collected with an acquisition time of 15-30 seconds with 300 mW laser power.

Citric acid, a well-known food additive, is selected here as a model system to study polymorphism based on two of its solid crystal phases: monohydrate and anhydrous, which crystallize from water at different temperatures[4]. Citric acid monohydrate and citric acid anhydrous were purchased from Sigma-Aldrich. The transition of the monohydrate form to the anhydrous was performed by heating the solid powder from room temperature to 80 °C.

Real-time monitoring and trending of the polymorphic transition of citric acid was done using B&W Tek’s BWSP-21pt11 software. This allows for continuous data collection and trending based on evolving PCA scores, chemometric models, or data trends. As the interest here is in following the transition (not quantitating the amount of the forms in the system during this process) we used the trend of the disappearance of monohydrate peak at 1108 cm^-1 and formation of the anhydrous form with the change in intensity of the new peak at 1146 cm^-1. There are other peaks specific to the monohydrate form including at 442, 820, 1167, 1260 and 2950 cm^-1 and for the anhydrous form at 1635, 2932 and 2982 cm^-1 that could be readily used to trend the transition. An overlay of spectra collected continuously as the temperature is increased to 80 °C is given in Figure 4. In the expanded view of the spectral region used for peak trending, the spectral changes on phase transition are evident in Figure 5. The trend of the monohydrate peak disappearance that was generated in real-time during data collection is given in Figure 6.

Because the spectral changes related to the change from the monohydrate to the anhydrous citric acid are not limited to discrete changes, a more holistic approach using multivariate data analysis, reflecting the systematic spectral changes with the increase in temperature can be captured using Principal component analysis (PCA). Using PCA analysis over the full spectral range, it is found that the first principal component explains 90% of the data variance over the course of the 75 spectra collected. A line plot of the score of PC-1 vs. sample spectrum shows the same trend as seen by following a single peak, and reflects changes across the Raman spectrum with the conversion for the monohydrate to anhydrous form. Figure 7 shows the plot of the PC-1 scores.

Here we show some examples of the value of Raman spectroscopy to monitor and identify different polymorphs. We used the portable i–Raman Plus with BWSP-21pt11 software for continuous monitoring and trending of the monohydrate to anhydrous transition of citric acid, with spectra collected every 15 seconds as the temperature was increased.