Crystallization and transitions of sulfamerazine polymorphs

A bulk powder of sulfamerazine polymorph II in a narrow distribution of particle size was prepared for the first time. The two known sulfamerazine polymorphs, I and II, were physically characterized by optical microscopy, powder X-ray diffractometry, differential scanning calorimetry, carbon-13 solid-state nuclear magnetic resonance spectroscopy, and measurements of aqueous solubility and density. The thermodynamics and kinetics of the transition between the polymorphs was examined under various pharmaceutically relevant conditions, such as heating, cooling, milling, compaction, and contact with solvents. The two polymorphs were found to be enantiotropes with slow kinetics of interconversion. The thermodynamic transition temperature lies between 51 and 54degreesC, with polymorph II stable at lower temperatures. Ostwald's Rule of Stages explains the crystallization of the polymorphs from various solvents and may account for the delay in the discovery of polymorph II. (C) 2002 Wiley-Liss, Inc.