Nanoindentation of Molecular Crystals: Lessons Learned from Aspirin.

Nanoindentation enables the measurement of mechanical properties from single crystals with dimensions of a few micrometers. This experimental technique, however, has only recently been applied to molecular crystals. Key differences between the application of this technique to molecular crystals and metals and other inorganics are identified. From this, protocols for the measurement of hardness and elastic modulus of molecular crystals of pharmaceutical interest are proposed. Using form I aspirin as a model system, the impact of single crystal sample surface preparation (washing and cleaving) on the surface roughness is explored. We show the importance of using a calibration sample with hardness and stiffness close to that of molecular crystals for the acquisition of more accurate data. The issue of solvent occlusions formed during crystal growth is discussed as a source of material property variation as well as tip contamination. It is proposed that this in part explains the significantly larger variation of the measured mechanical properties among different single crystals compared to those performed on a unique sample. Because both the indentation modulus and the hardness can vary significantly for low depth indents, samples were tested over a wide range of depths, which revealed that a minimum depth of penetration is required for the acquisition of data. This experiment is crucial and needs to be carried out for every system under study since it allows for the determination of the minimum-working load. Post-indentation imaging combined with crystallographic analysis and molecular simulations allows for the characterization and rationalization of the material plastic deformation mechanisms.