Utilization of Fourier transform-Raman spectroscopy for the study of pharmaceutical crystal forms

It is well understood that the solid state physical characterization of a drug substance is necessary for successful development and approval of a pharmaceutical product AAPS [1]. Physical analytical techniques used include: XRD, IR, DSC, TG, and NMR. Recently, Fourier transform (FT) Raman spectroscopy has become a more common technique. Complimentary to IR, FT-Raman can be used to differentiate between different crystal forms of a drug substance. FT-Raman exhibits several advantages over IR and the other physical analytical techniques. Very little sample is required with no preparation (dilution), analysis time is quick, and since water is a weak scatter (Raman spectrum of water contains three low intensity peaks), crystallization studies of drug substances from aqueous solutions can be performed. Additionally, through the use of a variable-temperature accessory, phase diagrams can be determined for crystal systems, leading to further characterization of those systems. This paper introduces the use of FT-Raman spectroscopy for pharmaceutical development activities. Specific examples will be shown for investigations of crystal forms (qualitative and quantitative) and crystallization studies.