Distribution of a viscous binder during high shear granulation--sensitivity to the method of delivery and its impact on product properties

Int J Pharm. 2014 Jan 2;460(1-2):255-63. doi: 10.1016/j.ijpharm.2013.11.020. Epub 2013 Nov 20.

Abstract

Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation.

Keywords: Binder distribution; Binder flow rate; Granule growth; Granule rheology; High shear granulation; Pressure pot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / chemistry
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Chlorpheniramine / chemistry
  • Drug Compounding
  • Excipients / chemistry
  • Hardness
  • Powders
  • Starch / chemistry
  • Tablets / chemistry*
  • Technology, Pharmaceutical*
  • Viscosity

Substances

  • Excipients
  • Powders
  • Tablets
  • Acetaminophen
  • Chlorpheniramine
  • Cellulose
  • Starch
  • hydroxypropylcellulose
  • microcrystalline cellulose