Fast time-resolved micro-CT imaging of pharmaceutical tablets: Insights into water uptake and disintegration

Abstract

We use dynamic micro-computed tomography (micro-CT) with a high temporal resolution to visualize water penetration through the porous network of immediate-release pharmaceutical solid tablets and characterize dynamic swelling and disintegration mechanisms. We process the micro-CT images using two theoretical scenarios that reflect different paths of pore structure evolution: a scenario where tablet porosity remains constant during the swelling process and a scenario where the tablet porosity progressively diminishes and eventually closes during the swelling process. We calculate the time evolution of the volume of water absorbed by the tablet and, specifically, absorbed by the excipients and the pore structure, as well as the formation and evolution of cracks. In turn, the three-dimensional disintegration pattern of the tablets is reconstructed. Restricting attention to the limiting scenario where tablet porosity is assumed fixed during the swelling process, we couple liquid penetration due to capillary pressure described by the Lucas-Washburn theory with the first-order swelling kinetics of the excipients to provide a physical interpretation of the experimental observations. We estimate model parameters that are in agreement with values reported in the literature, and we demonstrate that water penetration is dominated by intra-particle porosity rather than inter-particle porosity.

Keywords: Capillary flow; Dynamic micro-CT; Swelling; Tablet porosity; Water uptake.