On the Application of Strong Magnetic Fields during Organic Crystal Growth

We investigate the effect of crystal growth within a magnetic field for three polymorphic pharmaceuticals, using an experiment where the magnetic field can be varied in strength without altering other crystallization conditions. In the case of carbamazepine, fields above 0.6 T produce metastable form I, and for flufenamic acid, there is an increased propensity to crystallize metastable form I around 1 T. In contrast, the magnetic field has no effect on the crystallization of mefenamic acid, a closely related molecule. The growth of the metastable β polymorph of coronene within a magnetic field at ambient temperature is difficult to reproduce but has been seen as a minor component, consistent with this transformation to the more stable form being facile, depending on the particle size. Calculations of the diamagnetic susceptibility tensors of the polymorphs and their morphologies provide semiquantitative estimates of how the diamagnetic susceptibilities of crystallites differ between polymorphs and explain why mefenamic acid crystallization is unaffected. As the onset of crystallization of carbamazepine and coronene, as defined by changes in turbidity, occur at lower temperatures and hence greater supersaturations in certain ranges of magnetic field strength, this suggests that the field causes precipitation of the metastable form through Ostwald's rule of stages.