X-Ray Powder Diffraction (XRPD) is considered as the gold standard method in the field of pharmaceutical powders for the identification of solid forms (i.e. polymorphs, solvates, hydrates, salts, co-crystals, amorphous). When combined with a synchrotron X-ray beam, XRPD becomes a very powerful analytical tool, which significantly enhances the characterization of pharmaceuticals.
As a result of their manufacturing and storage conditions, pharmaceutical drug substances can exist in different crystalline forms (i.e. polymorphs). Polymorphism of drug can have a profound effect on the quality or performance (e.g. solubility, bioavailability, efficacy, safety) of the drug product and it is in fact a regulatory requirement to conduct a detailed analysis of the polymorphism of the drug substance and drug product during technical development.
Synchrotron XRPD offers the advantages of ultra-high FWHM and d-spacing resolutions, accurate 2q angle assignment, high signal-to-background and signal-to-noise ratios. When it is combined with new outstanding single-photon-counting detection systems, the measurements times is drastically reduced to milliseconds, allowing in-situ study of the kinetic of transformations and radiation-damage-free high-resolution diffraction patterns.
Advances in instrumentation, calibration and data collection procedures are discussed leading to detection limits of contaminating crystalline phases better than 0.05% wt% as well as the disclosure of subtle structural details. SR-XRPD technique and instrumentation applied to the study of pharmaceuticals is discussed together with relevant examples of applications. The modalities of the fast, easy and affordable access to these state-of-the-art analytical tools are also discussed.