Linking crystal structure to pharmaceutical performance: surface analysis of cannabigerol cocrystals
A feature article by Eliška Zmeškalová and colleagues, published in IUCrJ with an invited commentary, demonstrates how combining crystallography with modern computational tools can guide the design of better solid forms of pharmaceuticals.
The team investigated cannabigerol (CBG), a non-psychotropic cannabinoid with promising therapeutic effects but poor solubility and processing properties. By co-crystallizing CBG with pharmaceutically safe coformers, the researchers discovered two new cocrystals with markedly improved solid-state behaviour. In particular, the CBG–tetramethylpyrazine cocrystal exhibited a threefold increase in dissolution rate compared to pure CBG, pointing to improved bioavailability potential.
Using single-crystal diffraction, spectroscopy and thermal analysis in combination with computational surface modelling (CSD-Particle), the study revealed how differences in crystal packing and surface chemistry directly determine dissolution and manufacturability. Whereas pure CBG crystals expose mostly hydrophobic surfaces and grow as fragile needles, the new cocrystals present more hydrophilic surface groups and adopt block-like morphologies, making them both more stable and more soluble.
This work was carried out in close collaboration between the Institute of Physics of the Czech Academy of Sciences (FZU), the University of Chemistry and Technology in Prague (VŠCHT), and the pharmaceutical company Zentiva, showcasing the power of academic–industry partnerships.
By linking atomic-level crystal structures to macroscopic pharmaceutical performance, the study provides a blueprint for rational solid-form design. It highlights how integrated experimental–computational workflows can accelerate the digital design of drug crystals — reducing development risks and helping transform promising natural compounds into usable medicines.
Figure
The interactions of water molecules (represented as blue clouds) around more polar areas of a predicted particle surface (shown by the red regions) are linked to dissolution behaviour by Zmeškalová and coworkers.