Experimental investigation of wet pharmaceutical granulation using in-situ synchrotron X-ray imaging

Observing and measuring wet granulation processes of pharmaceutical powders is challenging with conventional experimental methods due to their opacity and the complex interaction that happens in a short time. In this study, synchrotron in-situ imaging technique was employed to capture the dynamic granulation process with a single drop impacting method. Two common pharmaceutical excipients and an active pharmaceutical ingredient (API) were used as the powder beds. Three liquids were used as binders. A new parameter, overall movement ratio, r_m, is introduced to quantitatively describe the movement of the liquid binders in the powder beds. The dynamic interactions between the liquid binder and solid powders were captured via high temporal and spatial resolution X-ray images. Results show that particles with smaller sizes have the tunneling mechanism, and the spreading mechanism occurs with larger particles, as expected. Liquid binder properties including viscosity and contact angle, and operation parameters including droplet release height and volume show significant impacts on the dynamic granulation process. This study demonstrates the potential of using in-situ synchrotron X-ray imaging to quantitatively study the dynamic wet granulation process.