A metastable polymorph of metformin hydrochloride: Isolation and characterization using capillary crystallization and thermal microscopy techniques

Capillary crystallization techniques and thermal microscopy have been used to identify and characterize a metastable polymorph of metformin hydrochloride. The single crystal structure of the metastable polymorph (Form B) is reported and compared to the known thermodynamically stable form (Form A). There is a 5.8% density difference between Form A and Form B. N-H...N hydrogen bonds form a ID rod motif in Form A as opposed to a OD dimer in Form B, while the charge-assisted N-H...Cl hydrogen bonds maintain a layered motif in both Forms A and B. The preferential generation of metastable solid phases is discussed in the context of classical nucleation theory.