Advanced 3D and 4D microstructure study of single granule formation for pharmaceutical powders using synchrotron x-ray imaging

Monitoring the microstructure of the granule in the wet granulation process could play a decisive role in obtaining high-quality granules. Due to the complex, fast and opaque nature of wet granulation, it cannot be captured by conventional methods. In this study, synchrotron x-ray imaging was employed for the first time to investigate the internal real-time pore evolution during the granule formation process, based on the single droplet impact method. It was found that granules from coarser and more homogenous powders experienced a higher rate of pore evolution during nucleation with a more uniform pore distribution. Dynamic wetting studies showed the granule formation mechanisms, the crater mechanism was found for most binary mixtures with 50 wt. % excipients. According to the physical tests, the granules with lower porosity and finer pores exhibited higher hardness and a slower dissolution rate.