Compression Density as an Alternative to Identify an Optimal Moisture Content for High Shear Wet Granulation as an Initial Step for Spheronisation.

Abstract

Pellet production is a multi-step manufacturing process comprising granulation, extrusion and spheronisation. The first step represents a critical control point, since the quality of the granule mass highly influences subsequent process steps and, consequently, the quality of final pellets. The most important parameter of wet granulation is the liquid requirement, which can often only be quantitatively evaluated after further process steps. To identify an alternative for optimal liquid requirements, experiments were conducted with a formulation based on lactose and microcrystalline cellulose. Granules were analyzed with a Powder Vertical Shear Rig. We identified the compression density (ρpress) as the said alternative, linking information from the powder material and the moisture content (R2 = 0.995). We used ρpress to successfully predict liquid requirements for unknown formulation compositions. By means of this prediction, pellets with high quality, regarding shape and size distribution, were produced by carrying out a multi-step manufacturing process. Furthermore, the applicability of ρpress as an alternative quality parameter to other placebo formulations and to formulations containing active pharmaceutical ingredients (APIs) was demonstrated.