Dingeman L.H. van der Havena, Jan L. Andreasenb, Ioannis S. Fragkopoulosc, James A. Elliotta.
a Department of Materials Science & Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge, CB3 0FS, United Kingdom
b Devices and Delivery Solutions, Novo Nordisk A/S, Hillerød, Denmark
c Oral Drug Product Process Development, Novo Nordisk A/S, Måløv, Denmark
Purpose: The shape and size of individual particles strongly affect the compaction behavior of pharmaceutical powder formulations, but detailed particle-scale characterization remains complex and time-consuming. Commonly used techniques such as optical microscopy, light scattering, and electron microscopy are limited by the need for unrealistic assumptions, e.g. spherical particle shape, or by providing only two-dimensional information. As a result, even the best quality control and modelling frameworks are unable to fully account for variations in particle shape and size.
Methods: A new sample-preparation method was developed to create a suspension of pharmaceutical powder particles. Subsequently, particles were scanned using X-ray computed microtomography (X-ray µCT) at a resolution of several micrometers. Other techniques such as optical microscopy were also performed to allow for a detailed comparison. Novel algorithms were developed and used to generate single-particle representations that were directly used in volume-interacting level-set discrete element method (VLS-DEM) simulations for estimating e.g. bulk densities.
Results: The new sample-preparation method produced well-dispersed particle suspensions, allowing easy identification of individual powder particles without the need for complex algorithms or calibration methods for particle separation. X-ray µCT resolved highly detailed 3D particle morphologies, providing superior information compared to conventional techniques. VLS-DEM simulations demonstrate how particle shape alone can affect bulk properties, leading to more accurate estimation of the bulk density.
Conclusions: The newly proposed X-ray µCT methodology is straightforward and allows for the 3D characterization of single-particle morphologies and sizes. This framework can be used to improve current quality control methods and simulations considering particle shape.