Multiscale X-ray imaging and characterisation of pharmaceutical dosage forms

A correlative, multiscale imaging methodology for visualising and quantifying the morphology of solid dosage forms by combining ptychographic X-ray computed nanotomography (PXCT) and scanning small- and wide-angle X-ray scattering (S/WAXS) is presented. The methodology presents a workflow for multiscale analysis, where structures are characterised from the nanometre to millimetre regime. Here, the method is demonstrated by characterising a hot-melt extruded, partly crystalline, solid dispersion of carbamazepine in ethyl cellulose. Characterisation of the morphology and solid-state phase of the drug in solid dosage forms is central as this affects the performance of the final formulation. The 3D morphology was visualised at a resolution of 80 nm over an extended volume through PXCT, revealing an oriented structure of crystalline drug domains aligned in the direction of extrusion. Scanning S/WAXS showed that the nanostructure is similar over the cross section of the extruded filament, with minor radial changes in domain sizes and degree of orientation. The polymorphic forms of carbamazepine were qualified with WAXS, showing a heterogeneous distribution of the metastable forms I and II. This demonstrates the methodology for multiscale structural characterization and imaging to enable a better understanding of the relationships between morphology, performance, and processing conditions of solid dosage forms.