Granule Formation, Structure and Content Uniformity from Single Drop Impact on Heterogeneous Powder Beds

Single drop impact of liquid on a static powder bed was studied to investigate the granule formation mechanism, droplet penetration time, the characterization of granules (morphology, surface structure and internal structure), as well as the formation regime map. Water was used as the liquid and two pharmaceutical powders, microcrystalline cellulose (MCC) and acetaminophen (APAP), were mixed to make heterogeneous powder beds. The complete drop impact and penetration was recorded by a high-speed camera. Two granule formation mechanisms identified previously occurred: Spreading and Tunneling. Spreading occurred for mixtures of large particle sizes, while Tunneling started to occur when the particle sizes of the mixtures decreased. With an increase of APAP concentration, the overall drop penetration time increased, which was in good agreement with previous literature. The granule morphology, surface structure, and internal structure were characterized by a prism method with image analysis, scanning electron microscope, and X-ray microtomography, respectively. The Spreading mechanism produced flat disks with porous internal structures, while the Tunneling mechanism produced round granules with dense internal structures. Granules that were formed via a hybrid of the mechanisms, Spreading/Tunneling, were hybrid granules, with some dense areas and some porous areas. The results of the granule content uniformity from UV-vis spectrometry revealed that with the increase of APAP proportion, the overall uniformity was compromised for mixtures with fine ingredients, while the content was much more uniform for coarse mixtures. It is believed that the mean particle size of the powder bed is the predominant factor in influencing the formation mechanism, drop penetration time, and granule properties, while the content uniformity is affected by both the particle sizes and the mixture hydrophobicity.