Drug development is a decades-long, multibillion dollar investment that often limits itself. To decrease the time to drug approval, efforts are focused on drug targets and drug formulation for optimal biocompatibility and efficacy. X-ray structural characterization approaches have catalyzed the drug discovery and design process. Single crystal X-ray diffraction (SCXRD) reveals important structural details and molecular interactions for the manifestation of a disease or for therapeutic effect. Powder X-ray diffraction (PXRD) has provided a method to determine the different phases, purity, and stability of biological drug compounds that possess crystallinity. Recently, synchrotron sources have enabled wider access to the study of noncrystalline or amorphous solids. One valuable technique employed to determine atomic arrangements and local atom ordering of amorphous materials is the pair distribution function (PDF). PDF has been used in the study of amorphous solid dispersions (ASDs). ASDs are made up of an active pharmaceutical ingredient (API) within a drug dispersed at the molecular level in an amorphous polymeric carrier. This information is vital for appropriate formulation of a drug for stability, administration, and efficacy purposes. Natural or biomimetic products are often used as the API or the formulation agent. This review profiles the deep insights that X-ray structural techniques and associated analytical methods can offer in the development of a drug.
Keywords: X-ray crystallography; active pharmaceutical ingredient; amorphous solid dispersions; drug products; excipients; pair distribution function.