CSD in Action: Understanding Important Particle Properties and Their Effects on Pharmaceutical Formulation and Manufacturing
September 27, 2022
In the latest in our 'Tools in Action' series — highlighting research that draws on the wealth of knowledge in the Cambridge Structural Database (CSD) and CCDC software to enhance and mine the data from the 1.1M+ crystal structures — a collaboration between five organisations used software now available in the CSD Particle suite to assess and predict particle properties that influence pharmaceutical formulation and manufacture.
The anhydrous form of the antiepileptic drug lamotrigine (CSD Refcode: EFEMUX01).However, the behaviour of lamotrigine during formulation and manufacturing presents many issues, including poor powder flow properties and poor compressibility - the latter leading to 'capping' upon tableting. Predicting and avoiding these issues in advance of manufacture will save pharmaceutical companies time and resources by reducing the amount of experimental research needed to try and identify these potential bottlenecks.
Particle Informatics WorkflowThe team used a combination of predictive digital tools now included in CSD Particle and methods that focus on intermolecular interaction energies, to propose a workflow that builds on the knowledge from each step to avoid these and other formulation issues in small molecule pharmaceutical manufacturing. Using lamotrigine as an example, each step of the particle informatics workflow is explained, providing insights into solid particle behaviour along the manufacturing journey. A thorough analysis of particle behaviour at each stage is presented, including:
- Intermolecular interactions and energetic analysis
- Mechanical property prediction and analysis
- Particle morphology calculation and analysis
- Surface energy and topology analysis
- Analysis of surface interactions.
The New CSD Particle Suite – Transform Pharmaceutical and Fine Chemical Manufacturing by Anticipating and Eliminating Potential BottlenecksRecently added to the CCDC software portfolio, the CSD Particle suite of informatics tools draws on the data from 1.1M+ validated crystal structures in the CSD to anticipate manufacturing bottlenecks and guide formulation decisions with a deep understanding of particle behaviour. Manufacturing bottlenecks anticipated include flow, wettability, tabletability and sticking.
Virtual Workshop – Understand the Mechanical and Surface Properties of ParticlesOn October 12th we are holding a virtual workshop on how to visualize and analyse particle and their surfaces. In this hands-on interactive workshop, examine the link between crystal structures and particles, and understand the mechanical and chemical properties of those particles. More information and registration can be found on the event page.
- Mathew J. Bryant, Ian Rosbottom, Ian J. Bruno, Robert Docherty, Colin M. Edge, Robert B. Hammond, Robert Peeling, Jonathan Pickering, Kevin J. Roberts, and Andrew G. P. Maloney, “Particle Informatics”: Advancing Our Understanding of Particle Properties through Digital Design, Crystal Growth & Design, 2019 19 (9), 5258-5266, DOI: 10.1021/acs.cgd.9b00654.
- Galek, P. T. A.; Pidcock, E.; Wood, P. A.; Bruno, I. J.; Groom, C. R., One in Half a Million: A Solid Form Informatics Study of a Pharmaceutical Crystal Structure, CrystEngComm 2012, 14 (7), 2391– 2403, DOI: 10.1039/C2CE06362J.