Pharmaceutical process applications of Raman spectroscopy

In the past decade Raman spectroscopy (Raman) has moved out of the shadow of infrared spectroscopy (IR) and has become a routine analytical tool and is finding value in pharmaceutical process applications. Raman offers several advantages over IR vibrational information in identifying and quantifying chemicals, such as linear response to concentration independent of path length, ability to measure aqueous solutions without interference from water bands, and ease of sampling provided by fiber optic probes. However, process measurements, such as continuous monitoring or raw materials identification have been slow to develop due to instability of the wavenumber axis. Commercial suppliers of dispersive based Raman systems employ calibration references and software approaches to solve this difficult problem. To overcome this difficulty, just as dispersive IRs have been replaced by FT-IRs, we have developed an industrial hardened FT-Raman system. Furthermore, we have increased sensitivity by 25 times by employing an Si detector instead of an InGaAs detector. Here we present the abilities of this Raman system to address a number of pharmaceutical applications, including identifying raw materials in less than one minute using spectral library matching, process monitoring during early stage optimization, analyzing blended materials, and determining polymorphism.