Small Crystals, Big Insights: How Electron Diffraction is Transforming Materials, Life Science, and Chemistry Research #4. Solving Pharma’s Toughest Solid Form Challenges with Electron Diffraction

In your drug development process, do you ever have to deal with very small amounts of highly imperfect and impure samples, where you are required to determine some structural information related to connectivity, polymorphism, disorder state?

If so, then electron diffraction may be the tool you have been waiting for.

Within the drug development process, especially with more complex molecular entities, there are many stages where the solids requiring characterization might be sub-milligram in weight, be impure and imperfect from a crystalline perspective, and exhibit nanometer sized particles. In many cases, these solids are ideal for Micro Electron Diffraction (MicroED, 3DED).

At the initial crystallization step in late discovery / early development, you may have small amounts of material with a multitude of crystalline polymorphs driven by the impurity profile. These crystals will likely be very small and imperfect. MicroED can provide the only realistic characterization tool for determining connectivity and crystal form. In addition, with automated crystal identification and measurement protocols, polymorph screens can be performed on these very first solids.

After milling or processing to reduce particle size (enhance flow characteristics and solubility) the crystal will again be very small and highly disorder. As disorder as well as size play a significant role in solubility, being able to characterize the level and type of disorder induced by processing can be critical in optimizing scale up and manufacturing. MicroED is able to characterize induced disorder through automated analysis of individual particles.

The application of MicroED to characterize these types of samples will be discussed along with examples of measurements on nanoparticle delivery systems.