The Crystal Chemistry and Particle Sciences of Drug Product Processing: The Cambridge Structural Database Meets the Manufacturing Classification System

An understanding of the materials science of a new active pharmaceutical ingredient is crucial at the interface between chemical synthesis and drug product development. The physical and chemical properties of a new chemical entity, either as the active pharmaceutical ingredient or the drug product, are strongly influenced by the particle attributes and the underlying crystallization process defined during development. Product performance can be assured only when the active ingredient is delivered to the patient in a chemically and physically stable particle. A structural understanding in this key area allows pharmaceutical organizations to support the selection of the right molecule from discovery, design of the right product during development, and optimization of the manufacturing process in production. Accelerated pharmaceutical development, with clear clinical biomarkers, reduced attrition, increased number of projects, and diversity of dosage forms, will heighten the scientific challenge across the pharmaceutical sciences community, in particular at the interface between the active ingredient and the drug product. In this paper, we reimagine the molecule to medicine journey, highlighting progress on the application of Particle Informatics. We demonstrate the crystallographic data thread through development by linking the Manufacturing Classification System back into the Cambridge Structural Database. This demonstrates the potential for Particle Informatics applications to connect across the chemical, analytical, and formulation disciplines, providing a cornerstone for the accelerated development and manufacture of novel advanced pharmaceutical products.