Spectroscopic Methods in Solid-state Characterization

Summary This chapter describes the principles and applications of spectroscopic methods used to probe solid-state structure of particulates. The methods include mid-infrared, near-infrared (NIR), terahertz, Raman, fluorescence, and solid-state nuclear magnetic resonance spectroscopies. The majority of NIR imaging applications for pharmaceutical particle characterization have involved chemical analysis. They include drug and excipient distributions in powders, roller compacted ribbons, extrudates, tablets and printed products, as well as the detection of counterfeit product. Terahertz spectroscopy has been used to detect and quantify different crystalline solid-state forms including polymorphs, solvates (including hydrates), and co-crystals, as well as the amorphous form. Raman spectroscopy is a routine solid-state characterization technique in pharmaceutical research and development, manufacturing, and quality control of finished products. The chapter also discusses nonlinear optics encompassing several nonlinear phenomena such as second harmonic generation, coherent anti-stokes Raman scattering and two-photon excited fluorescence.