One in half a million: a solid form informatics study of a pharmaceutical crystal structure

Abstract

We introduce a knowledge-based approach to the evaluation, analysis and prediction of the properties of a crystal form; described inclusively as Solid Form Informatics. This approach is exemplified using the recently published crystal structure of the drug lamotrigine in the context of the Cambridge Structural Database (CSD). Analysis at the molecular, intermolecular and supramolecular level is carried out using the range of software available in the CSD System alongside new research applications. This work provides a template for the thorough analysis of any crystal structure and paves the way toward a fully automated structural analysis for the drug formulation scientist, with the aim to better provide answers to the fundamental questions raised during the drug development process. To conclude, the knowledge gained about the structure is applied to predict the potential for a co-crystal formulation of the drug and to automatically select optimal co-crystal formers. The crystal structure of lamotrigine was the half-millionth structure to enter the CSD. We demonstrate how the 499,999 structures that preceded it are central to the analyses presented.