X-Ray Crystallography and its Role in Understanding the Physicochemical Properties of Pharmaceutical Cocrystals

Properties of a matter are intrinsically dependent on the internal arrangement of molecules in the solid state. Therefore, knowledge of three-dimensional structure of the matter is a prerequisite for structure–property correlations and design of functional materials. Over the past century, X-ray crystallography has evolved as a method of choice for accurate determination of molecular structure at atomic resolution. The structural information obtained from crystallographic analysis paved the way for rapid development in electronic devices, mineralogy, geosciences, materials science, pharmaceuticals, etc. Knowledge of the structural information of active pharmaceutical ingredients (APIs) is a prerequisite for rational drug design and synthesis of new chemical entities for development as new medicines. Over the past two decades, X-ray crystallography has played a key role in the design of pharmaceutical cocrystals—crystalline solids containing an API and one or more of pharmaceutically acceptable coformers. These materials have proved promising for fine-tuning several important properties of APIs. This short review highlights the history of crystallography, early breakthroughs, and the role of crystallography in understanding the physicochemical properties of pharmaceutical cocrystals.