Amorphous characterization of pharmaceutical drug substances enabled by the elastic modulus mapping of atomic force microscope.

The states of amorphous drug and/or newly generated crystalline drug on the surface of amorphous drug samples must be carefully characterized to validate the quality of pharmaceutical amorphous drugs. In this study, we investigated whether individual mechanical properties of amorphous and crystalline drugs could be discerned by an atomic force microscope (AFM) with a mapping. Among mechanical properties, the amorphous and crystal drugs were quantitatively distinguished by elastic modulus using PeakForce quantitative nanomechanical mapping. The elastic modulus of the crystals exceeded 10 GPa-significantly higher than that of the amorphous, which was ≤5 GPa in all five model drugs; consequently, ≤200 nm scale crystals were detected on amorphous surfaces. Furthermore, the elastic modulus reflected the difference in the amorphous states between the molten and the solvent-evaporated preparations in the microscopic area, thereby demonstrating the ability of AFM to characterize amorphous states. Taken together, AFM measurements using elastic modulus can be an effective analytical tool to provide microscale mapping and characterization of amorphous surfaces, leading to enhanced amorphous drug development.