Granulation of hydrophobic powders is a growing problem in the pharmaceutical industry. The structural complexity of new drug molecules mean that is increasingly common for entire classes of drug compounds to be highly hydrophobic. This creates considerable difficulty in understanding, controlling and trouble-shooting these industrial granulation processes.

There have been many recent advances in granulation theory (Litster and Ennis, 2004), but it is assumed that wetting and spreading of the fluid through the powder particles is a prerequisite for good granulation. The possibility of a fine, hydrophobic powder spreading over the surface of the liquid during nucleation has been identified theoretically based on surface chemistry (Rowe, 1989) and as a potential nucleation mechanism (Hapgood 2000, Simons and Fairbrother, 2000). Recently, investigation confirmed that nucleation can occur by spreading of the sub-micron particles around the template drop (Farber et al., 2006). This unique nucleation behaviour, called “solid spreading nucleation”. The hollow granule structure formed by the solid spreading mechanism is unique and suggests the possibility of using the controlled, open granule structure to manufacture “designer pharmaceutical particles” with a number of advantageous properties: 1. Controlled granule size by manipulating the size distribution of the spray drop “templates” 2. Controlled granule structure by exploiting the solid spreading mechanism. This allows for the potential for designer pharmaceutical particles, with controlled size distribution and excellent ideal flow and handling properties.

This paper will describe progress to date on single drop solid-spreading nucleation experiments, where single fluid droplets are placed onto loosely packed powder beds of hydrophobic powders and the formation of the powder shell observed via high speed video camera. Experimental results for a model hydrophobic system will be presented together with an explanation of the behaviour observed and implications for granulator control.