Quantifying liquid coverage and powder flux in high-shear granulators

Abstract

A key aspect to high-shear wet granulation is the coverage of binding fluid as it first comes into contact with the surface of a powder bed. Quantifying the parameters that determine liquid coverage with respect to powder flux could improve the ability to rationally characterize and scale wet granulation processes. In this work, the surface velocity of a powder bed was measured during wet granulation in high-shear mixers (Aeromatic-Fielder) ranging from lab (25 l) to pilot (300 l) scale. High-speed video analysis revealed that surface velocity is strongly dependent on impeller speed, mixer scale, fill level, and extent of granulation. Surface velocity results were coupled with the dimensionless spray flux concept reported by Litster et al. [Powder Technol. 114 (2001) 32] to quantify liquid coverage relative to powder flux for operating conditions commonly used to granulate pharmaceutical powder blends. Dimensionless spray flux calculations suggest that granule nucleation in high-shear mixers does not take place in the drop-controlled regime. The density of spray drops at the surface of the powder bed is sufficiently high to cause a significant amount of drop overlap, thereby hindering the formation of nuclei from individual spray drops. Dimensionless spray flux calculations predict an approximate 2.5-fold increase in liquid coverage upon scaling a standard high-shear wet granulation process from 25 to 300 l. The use of multiple spray nozzles could potentially minimize differences in liquid coverage between scales. Practical limitations of the dimensionless spray flux concept are discussed and an empirically modified version of the original spray flux equation is presented.