By NanoMEGAS SPRL
NanoMEGAS publishes case study on determining crystal structure of pharmaceuticals using 3D precession diffraction tomography (PEDT)
Brussels, Belgium: – World-leading instrumentation hardware and software specialist and innovator in electron diffraction and Transmission Electron Microscopy (TEM) NanoMEGAS SPRL, has published a case study showing how 3D Precession Electron Diffraction Tomography can reveal the crystalline structures of pharmaceutical substances.
The case study is based on scientific research ‘Crystal Structures of Two Important Pharmaceuticals Solved by 3D Precession Electron Diffraction Tomography’ published in the journal organic process research and development (https://pubs.acs.org/doi/abs/10.1021/acs.oprd.8b00149).
The research was led by NanoMEGAS scientists, joined by researchers from Italy’s Center for Nanotechnology Innovation in Pisa, The Romanian National Institute for R&D of Isotopic and Molecular Technologies in Cluj and Romania based Solid State and Crystallization service company Teracrystal.
The study focuses on the crystal structures of two important marketed pharmaceuticals, ramelteon (RAM) and tolvaptan (TOL), as examples of determining unknown structures using diffraction data collected from 3D precession electron diffraction tomography (PEDT).
The results were compared with the same structures determined by single-crystal X-ray diffraction on subsequently grown 50−200 μm single crystals, indicating a good match of molecular conformation, crystal packing, and unit cell parameters.
PEDT as standalone tool
The X-ray crystal structures were used to validate the developed workflow of data acquisition, data processing and structure solution with electron diffraction.
The case study demonstrates that 3D PEDT using TEM forms a unique tool that can provide accurate crystal structures from pharmaceutical nanocrystals that will suffice for most practical applications when no larger crystals can be grown.
The study reveals two different acquisition protocols designed for beam-sensitive materials, respectively based on sample cooling and ultrafast continuous data acquisition, can be adopted and deliver comparable results.
In particular, the study demonstrates that Simulated Annealing (SA) provides the basis for a robust protocol for structure solution that can be used to determine the atomic structure also for non optimal data when standard direct methods fail.
The case study emphasizes the potential of the 3D PEDT technique to provide accurate crystal structures of pharmaceutical nanocrystals for most practical applications when no larger crystals can be grown.
NanoMEGAS now envisages standard use of TEM-electron diffraction to identify small amounts of newly appearing polymorphs in batches prone to polymorphic transformations.
Brussels-based instrumentation hardware and software manufacturer NanoMEGAS SPRL (NM) is a specialist and innovator in advanced electron diffraction technologies in Transmission Electron Microscopy (TEM), with exciting applications for the pharmaceutical industry.
NanoMEGAS produces and distributes hardware and software solutions for TEM applications that can be used for academic and industrial characterization of nanocrystalline and amorphous nanomaterials for pharmaceuticals and for polymorphic analysis. NM also provides scientific consulting for pharmaceutical companies wishing to characterize nano-crystalline and amorphous pharmaceuticals.
NanoMEGAS was founded in 2004 by a team of scientists and experts in the field of electron crystallography and catalysis. Inspired by pioneering work carried out on electron crystallography using precession electron diffraction at Bristol, UK at 1996 the NanoMEGAS team was first to develop and market its “spinning star” universal precession device for TEM in 2004. Today, there are more than 220 installations worldwide and more than 1500 scientific publications related with NanoMEGAS applications & instrumentation in various fields, including pharmaceuticals.
Learn more at https://nanomegas.com
Click on Crystal Structures of Two Important Pharmaceuticals Solved by 3D Precession Electron Diffraction Tomography to read full study.