Experiments on semiconductors reveal a new way to study and control crystallisation. The discovery has relevance to pharmaceutical manufacturing as many drugs are made from small molecules that must crystallise in just the right way to have the proper effect.
Stanford engineers wished to understand how they created an electronically useful crystal lattice and wanted to record and visualise crystal formation. To capture the growth process, they fired a tiny, bright X-ray beam produced by the Cornell High Energy Synchrotron Source (CHESS) in Ithaca, New York. They focused the beam on a very small spot and fired at intervals a few milliseconds apart.
They took snapshots of the crystallisation process revealed by the beam using a high speed X-ray camera and reassembled the snapshots to create an animated movie revealing the story of crystallisation and how organic molecules form different types of ordered crystals, according to a paper in Nature Communications .
The Stanford group dissolved organic molecules in a solution and deposited this onto a flat surface. “As the solution dried in less than a second, millisecond resolution was necessary to study the evolution of crystal polymorphs in detail,” explains Gaurav Giri , first author of the paper at Stanford University, and now at MIT.
“We study this process in the context of organic electronics, where crystals of organic small molecules can transport current as semiconductors,” he notes. There is relevance here to pharmaceutical compounds.
“For organic electronics, the precise crystal structure controls the electronic properties of the semiconductor. Similarly, the precise crystal structure of pharmaceutical compounds control many physical properties that are important for drug delivery, such as drug stability, drug dissolution and ease of delivery in the body,” Giri observes.
“The FDA requires the exact crystal polymorph present in a drug for this reason. Our method will be helpful in understanding the crystallisation behaviour of drugs as well,” he adds. For example, the insights gained for confinement during drying, as well as the solvent effects, should be applicable to predict and control polymorphism in pharmaceutical compounds.
The approach “could also be deployed to good effect in drug development, where selection of crystal forms and polymorph screening is carried out,” comments Alastair Florence at the University of Strathclyde, UK. “The method potentially could be used to identify new or different polymorphic forms of new drug compounds allowing the best crystal form for further testing and product development to be identified quickly and produced at the required scale.”
Greater understanding of how the outcome might be affected by impurities would be required in the context of drug manufacture, Florence notes. “Also it would be necessary to ensure the correct polymorphic form is produced consistently as well as how the thin film might be processed to deliver a powder of consistent particle size for further processing.” It would be interesting to look at how this thin film approach might open up new processing techniques for delivering alternative manufacturing approaches for novel dosage forms, however, he concludes.