MicroED for Solid State Testing

The crystallographic structure has unparalleled advantages for selecting the dominant stable crystalline form, and it is rarely possible to obtain perfect crystals of each solid form for single-crystal resolution in the early stage of drug development. MicroED technology can bypass the time-consuming and laborious process of single-crystal incubation and directly resolve the structure of powder crystals at the early stage of drug development.

Figure 1. Comparison of the predicted (blue, red) and experimental (black) XRPD patterns (A and B) and structural overlay (C and D) of the predicted polymorph X1 with form IV (RMSD = 0.368 Å) and X2 with form II (RMSD = 0.441 Å) MicroED structures. (Sekharan, S., et al., 2021)

MicroED is a new tool for solid-state screening of small molecules in the field of drug discovery. Due to the high efficiency and universality of the test, MicroED can perform structural analysis of the obtained tiny crystals at the early stage of screening. It can predict the physicochemical properties and process feasibility of different drugs based on their solid-state structures, and achieve the initial screening of superior crystalline forms, while preparing for the drug declaration, thus accelerating the solid-state research of small molecule drugs.

In conventional solid-state research, the timing of obtaining crystal structures is usually after extensive screening experiments and characterization of the properties of each solid-state form, only the dominant crystal type is cultured as a single crystal, and then the structure of the crystal is resolved.

Creative Biostructure can predict the differences between the physical and chemical properties of different drug solid forms, such as melting point, density, pressure resistance, etc., by resolving the crystal structures of microcrystals through MicroED at an early stage of the drug solid-state development. This not only saves you resources in growing single crystals but also allows you to perform a preliminary screening of the dominant crystalline form of a drug before stability and process feasibility assessment work, thus avoiding a large investment of resources. Please contact our staff for more information.

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References

1. Sekharan S, et al. Selecting a stable solid form of remdesivir using microcrystal electron diffraction and crystal structure prediction. RSC Advances. 2021. 11(28): 17408-17412.