Physical characterization of pharmaceutical solids by Raman spectroscopy

It is increasingly important to fully characterize solid state pharmaceutical systems at the bulk, particulate, and molecular levels. A thorough characterization of the bulk drug at the onset of drug development may save significant time and alleviate a myriad of problems during later stages of development. As with any solid state investigation, a multi-disciplinary approach must be adopted to fully characterize the system, whether it be polymorphic, pseudopolymorphic, or a salt selection process. Typically, techniques such as XRPD, thermal analysis, micromeritics, and spectroscopy are used. At the molecular level, solid- state spectroscopy techniques are being widely used, specifically IR, NMR, and more recently, Raman spectroscopy. This discussion will focus on the use of Raman spectroscopy for the physical characterization of pharmaceutical solids. Descriptions of various experimental procedures will be highlighted by referring to examples of specific solid state characterization problems. An overall approach to polymorphic characterization and quantitation will also be outlined including requirements for a regulatory filing of a quantitative assay.