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

Abstract

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.