abstract
- The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH® 101) in a formulation with spray-dried α-lactose monohydrate (Flowlac® 100) in regards to wetting and granule nucleation for this relatively new technique known as continuous foam granulation. Foam stability was varied within the work to change its drainage and coarsening behavior atop these powder excipients, by use of different foamable binding agents (METHOCEL™ F4 PLV and METHOCEL™ Premium VLV) as well as by adjusting the foam quality. A static bed penetration test was first used to study the foam behavior in wetting these powders without the processing constraints of an extruder which limit possible liquid-to-solids ratios as well as introduce shear which may complicate interpretation of the mechanism. The test found that the penetration time to saturate these powders decreased as their water absorption capacity increased which in turn decreased the size of the formed nuclei. Differences in the stability of the foamed binder had minimal influence on these attributes of wetting despite its high spread-to-soak behavior. The size of granules produced by extrusion similarly demonstrated sensitivity to the increasing water absorption capacity of the filler and little dependency on foam properties. The different liquid-to-solids ratios required to granulate these different formulations inside the extruder highlighted an evolving concept of powder lubricity for continuous foam granulation.