X-ray diffraction as a tool in the path from the design of an active pharmaceutical ingredient to the tablet on the shelf

Accurate knowledge of molecular structure is a prerequisite for rational drug design. X-ray diffraction has a paramount importance in providing the required structural information: the structural determination by X-ray diffraction of new drug candidates and intermediates can provide valuable information of new syntheses and parameters for quantitative structure-activity relationships. Macromolecular X-ray crystallography is an important and powerful technique used in the discovery of new medicines. The detailed analysis of crystal structures of protein-ligand complexes allows the study of the specific interactions of a particular drug with its protein target at the atomic level. Most marketed pharmaceuticals consist of molecular crystals. The arrangement of the molecules in a crystal determines its physical properties and greatly influences the processing and formulation of solid pharmaceuticals, as well as key drug properties such as dissolution rate and stability. X-ray diffraction is the main tool to characterize the drugs in solid forms. An example of the use of X-ray diffraction in the development of rifamycins is discussed. © 2012 Accademia Nazionale dei Lincei.