4D study of liquid binder penetration dynamics in pharmaceutical powders using synchrotron X-ray micro computed tomography

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

“…The porosity values of dry granules are shown in Figure 10A. For most of the binary mixtures, the overall trend of porosity changes in the granules (upward or downward) is the same as the trends for the powder bed porosities seen in our previous work 22 . LMH, particularly LMHF, acted as the solid binder, effectively binding the particles and producing final granules with lower porosities 43 .…”

“…The liquid droplet penetrates the capillary pores to form the saturated nuclei, and the lower the contact angle and more uniform the pores inside the powder, the faster the resulting wetting and nucleation process 1 . By increasing the amount of active component, the penetration time increased for all compositions, as the distribution of the pores became less uniform and the contact angle increased 22 . Regardless of the powder bed porosity, the contact angle played a vital role in wetting, and MCC and MCCF, having a lower contact angle with water (more hydrophilic and higher preferential wetting) experienced much faster penetration, consistent with the literature 1 …”

“…Additionally, in the same powders, in most of the 90% fractions, the pores enlarged faster than in the 50% fractions. According to the previous study, 22,38 generally coarser and more homogeneous (90% excipient) powders have more uniform particles and pore distribution along axes in the powder bed, in which the wetting and nucleation will take place smoothly and pore size enlargement would be faster and easier. Also, the granulation mechanism showed an important impact on the pore evolution; if the granule was closer to the bed surface and no droplet was trapped inside, the evaporation of the binder would also play an important role in accelerating the (Continues) pore evolution.…”

“…The liquid binder was deionized (DI) water, one of the most common liquid binders. Similar to our previous work, 22 agglomerates were firstly removed from all powders through a 1 mm opening size sieve when making binary mixtures. Fine excipients (MCCF and LMHF) were achieved by sieving MCC and LMH through a sieve with an opening size of 38 μm.…”

“…The ρ bed was measured as the weight per volume in a 100 ml graduated cylinder, after pouring the powder through a plastic funnel at a height of 2 cm and leveling the surface. The particle AR (maximum width/minimum width) was measured based on SEM images presented in our previous work, both fine and coarse particles have similar shapes, so AR was measured just for course ones 22 . The powder‐liquid contact angles are taken from our previous work 26 .…”