Determination of the crystallographic orientation of organic crystal facets with angle-resolved polarised Raman spectroscopy

Abstract

Controlling the material properties of crystalline pharmaceutical materials is essential for developing materials with robust performance and manufacturability. Identification of the crystal facets present in a material opens up the opportunity for developing strategies to control and engineer material to meet manufacturing needs. This proof of concept study presents a workflow for using powder X-ray diffraction (PXRD) and angle resolved polarised Raman spectroscopy (ARPRS), in combination with density functional theory (DFT) calculations, to identify facets in samples unsuitable for single-crystal face indexing with XRD. Using Paracetamol (PCM) form I as a model compound, we demonstrate how preferred orientation effects in PXRD can be used with ARPRS measurements at different sample orientations, obtained by rotating in the plane perpendicular to the laser incidence direction, to define facet assignments from a set of possible planes. PXRD alone cannot distinguish the (011) and (01) facets, but these can be differentiated with ARPRS by analysing the change in normalised band intensity of selected vibrational modes under crystal rotation. Information on the symmetry and orientation of vibrational modes relative to the incident laser can be related to the orientation of functional groups, and this information is consistent with the predicted particle morphology as well as with measurements of the interfacial angle between the facets and corresponding Miller planes.