Molecular Crystallization within the Electrical Double Layer

Abstract

The polymorphic phase of crystals underpins key attributes of drug solubility, bioavailability, stability, and downstream processing. This work aims to model a parallel plate cell on an electrolytic capacitor design to develop large electric fields within the electric double layer interfaces to position paracetamol molecules into Form II orthorhombic polymorphs. Form II has been shown to have higher solubility and is readily compressible into tablets, thus making it more favorable.The parallel plate electrical double layer cell successfully delivers electric fields on the order of 1 V/nm to a thin layer solution. Electrochemical characterization demonstrates the long-term stability of the cell, dielectric breakdown, and overall electric field intensities that can be applied to solution. Application of this cell to a ring opening epoxide reaction and the resulting modulation of product ratios highlights the effectiveness of the cell. Efforts to affect crystal molecular nucleation are described in the context of supersaturated solutions of paracetamol subject to electric fields for 4-12 hours with temperatures from room temperature to -6 C. Raman spectroscopy and X-ray diffraction characterization of the crystals are used to confirm polymorph identity.