Applications of synchrotron powder X-ray diffractometry in drug substance and drug product characterization

Abstract

While X-ray powder diffractometry (XRD) is a powerful technique for characterizing crystalline phases, the sensitivity of the laboratory instruments can be a serious limitation. The use of synchrotron radiation has substantially enhanced its utility and synchrotron XRD (SXRD) has emerged as a powerful tool for analyzing pharmaceutical materials. The numerous applications of SXRD in both drug substance and drug product characterization have been comprehensively summarized. The applications are categorized into three areas: 1) Detection, characterization and quantification of multiple physical forms of the API in the DS. 2) Similar investigations in complex and multicomponent drug products. 3) Characterization and quantification of phase transformations during processing and storage. Thus, SXRD based studies have assisted pharmaceutical development by enhancing the understanding of mechanisms and kinetics of phase transformations during various pharmaceutical unit operations including crystallization and freeze drying. Subtle and nuanced information has been obtained during DP dissolution and long-term stability studies.