Application of X-ray diffraction methods in pharma industry

prof. RNDr. Bohumil Kratochvíl, DSc.
Ing. Jan Čejka, Ph.D.
Ing. Václav Eigner, Ph.D.
Yelizaveta Naumkina, MSc. (PGS)

Powder X-ray diffraction, crystal structure prediction

doc. Dr. Ing. Michal Hušák
Ing. Jan Rohlíček, Ph.D.

Team description:

X-ray single-crystal diffraction and pharmaceutical screening

The group is engaged in the application of X-ray structural and phase analysis in pharmaceutical research, development, production and control. It is equipped with a modern X-ray single-crystal diffractometer (bought within the KvaLab program), Bruker D8 Venture with two Incoatec microfocus Mo and Cu sources, a Photon 100 detector (Figure 1) and an older Xcalibur PX diffractometer (Figure 2).

The group has access to X-ray powder diffractometers (Bruker AXS, Philips X'Pert), in collaboration with the UCT Prague Central Laboratories – the X-ray Diffractometry Laboratory (Dr. Jaroslav Maixner). The research group cooperates with several pharmaceutical manufacturers in the Czech Republic (Teva Czech Industries Ltd., Zentiva LP etc.).

                  Fig. 1.: Bruker D8 Venture                                                                    Fig. 1.: Xcalibur PX

The group deals with the monitoring of polymorphism of active pharmaceutical substances by X-ray diffraction analysis and development of this methodology (newly: solution of crystalline structures of substances from X-ray powder diffraction data). The results of the studies are applied for molecular packing of polymorphs, for the research of the flexibility/rigidity of biologically active molecules, for the modeling of cavities in crystalline structures of substances and for their filling with solvent molecules, the development of specialized crystallographic software, the modeling of interactions of some substances with the receptors, in selected crystallizations, and microscopic observations.

Active pharmaceutical ingredient - API screening

Wide range of methods is used for the screening of new API forms, including crystalization from solution, slurry experiments, melt crystallization, post milling, sublimation (vapour deposition) and robotic screening.

Rtg. difrakce práškových materiálů, teoretické výpočty krystalové struktury

Structure solution of ixazomib and selexipag from powder diffraction data

We had successfully solved structures of 3 important pharmaceutical phases from data measured at European synchrotron radiation source (Grenoble). The mentioned phases are 2 modifications of ixazomib and crystal structure of selexipag. The solved structures complexity is on the edge of the used methodology.

Verification of crystal structure solution results based on DFT calculations

We work on method for verification of crystal structures solution based on the DFT calculation usage. The tested method is based on comparison between the experimental crystal structure and theoretical structure obtained as the result of lattice energy minimization. We are able to distinguish in this way e.g. cocrystal and salts or detect incorrectly solved structures. The calculation require extreme computation power - we use the national supercomputer Salomon (IT4innovations, Ostrava).