Revealing a pressure-induced reversible polymorph transformation by monitoring in-die density during powder compression

The reversible pressure-induced phase transformation of urea during powder compaction was investigated using a compaction simulator. The reversible change in solid density observed between 600 MPa and 900 MPa is consistent with the known pressure-induced reversible phase transformation between urea forms I and III. These findings establish compaction simulation as a material-sparing method for detecting pressure-induced phase transformations of active pharmaceutical ingredients during tableting, provided that the density change due to the polymorphic form transition is sufficiently large.