Scalability and Predictability of Polymorph Transformations Under High Shear

We show that the behavior of a polymorphic transformation under high shear can be predicted up to pilot scales on the basis of laboratory experiments. Solubility measurements indicate that the transformation rate is promoted at higher temperatures and that within the studied temperature range, the thermodynamically preferred form exhibits retrograde solubility. High shear, introduced both by a rotor-stator combination and by the use of high-surface area seeds, promotes the transformation, resulting in shorter transformation times. Raman spectroscopy data indicate that the transformation is dissolution limited. Correlations of the transformation time with changes in the total energy input to the crystals by collisions with the mill demonstrate that accounting for the seed surface area is necessary to model the experimental laboratory data. The transformation time for all pilot scale runs (103 scale higher than lab experiments) is well represented by the aforementioned model. This strategy for the promotion of a kinetically limited polymorphic transformation can potentially be extended to describe other solid–liquid suspensions under high shear.