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 2Ɵangle 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.
We also discuss the experience of Excelsus Structural Solutions in bringing these techniques and analyses successfully at the service of pharmaceutical and chemical companies. The modalities of the fast, easy and affordable access to these state-of-the-art analytical tools are also discussed.