UTILIZATION OF FOURIER-TRANSFORM RAMAN-SPECTROSCOPY FOR THE STUDY OF PHARMACEUTICAL CRYSTAL FORMS

It is well understood that the solid state physical characterization o f a drug substance is necessary for successful development and approva l of a pharmaceutical product AAPS [I]. Physical analytical techniques used include: XRD, IR, DSC, TG, and NMR. Recently, Fourier transform (FT) Raman spectroscopy has become a more common technique. Compliment ary to IR, FT-Raman can be used to differentiate between different cry stal forms of a drug substance. FT-Raman exhibits several advantages o ver IR and the other physical analytical techniques. Very little sampl e is required with no preparation (dilution), analysis time is quick, and since water is a weak scatter (Raman spectrum of water contains th ree low intensity peaks), crystallization studies of drug substances f rom 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 syst ems. This paper introduces the use of FT-Raman spectroscopy for pharma ceutical development activities. Specific examples will be shown for i nvestigations of crystal forms (qualitative and quantitative) and crys tallization studies. (C) 1998 Elsevier Science B.V. All rights reserve d.