Granule formation and structure from single drop impact on heterogeneous powder beds

Int J Pharm. 2018 Dec 1;552(1-2):56-66. doi: 10.1016/j.ijpharm.2018.09.036. Epub 2018 Sep 18.

Abstract

Single drop impact of liquid on a static powder bed was studied to investigate the granule formation mechanism, droplet penetration time, as well as the characterization of granules (morphology, surface structure and internal structure). 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 that have been identified previously occurred: Spreading and Tunneling. Spreading occurred for mixtures with an APAP amount of less than 20%, while Tunneling started to occur when the APAP amount increased above 20%. With an increase of APAP concentration, the mean particle size decreased, drop penetration time increased, and the granules formed became smaller in size, 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 microscopy (SEM), and X-ray microtomography, respectively. The Spreading mechanism produced flat disks with a porous internal structure, while the Tunneling mechanism produced round granules with a dense internal structure. There is a clear trend of decreasing porosity and increasing roundness of granules made from heterogeneous mixtures within the transition from Spreading to Tunneling. It is believed that the mean particle size of the powder bed and the powder-liquid contact angle are the predominant factors in influencing the formation mechanism, drop penetration time, and granule properties.

Keywords: Drop penetration time; Granule morphology; Granule porosity; Single drop granulation; Spreading; Tunneling; X-ray microtomography.

MeSH terms

  • Acetaminophen / chemistry
  • Cellulose / chemistry
  • Drug Compounding / methods*
  • Excipients / chemistry
  • Particle Size
  • Powders / chemistry*
  • Surface Properties
  • Water / chemistry

Substances

  • Excipients
  • Powders
  • Water
  • Acetaminophen
  • Cellulose
  • microcrystalline cellulose