Solution Mediated Polymorphic Transformation of Cefaclor: Insights into the Interaction Between Polymorph Surfaces

The solution mediated polymorphic transformation (SMPT) of the cefaclor monohydrate metastable Form I to the stable Form II was investigated in ethanol–water mixture. During the transformation for a variety of initial conditions, bulk transformation experiments were performed by Raman to monitor the polymorphic composition combined with UV to analysis of the solution concentration over time. The main factors studied were solvent composition, temperature, the scale of operation, mass of solids loading as well as pretreatment of the loaded solids. The results revealed that the transformation time was governed by the nucleating and growth behavior of the stable Form II across the range of experiments. The stable Form II is consistent nucleated epitaxially on the metastable Form I during the transformation. Microscopic techniques, single-crystal X-ray diffraction and computational simulation methods were used to analyze the transformation and epitaxial behavior. However, no specific lattice matching or epitaxy was conclusively identified. Therefore lattice matching may not the dominant reason for the nucleation of Form II on the surface of Form I. Molecular simulation is carried out to understand the different probabilities of the Form II nucleation on the surfaces of Form II at the molecular level.