A Metastable Polymorph of Metformin Hydrochloride: Isolation and Characterization Using Capillary Crystallization and Thermal Microscopy Techniques

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Abstract

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 1D rod motif in Form A as opposed to a 0D 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.

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