Microstructure of micro-crystalline cellulose based granules produced by high-shear wet granulation with long wet-massing time

Abstract

Design and scale-up of batch high-shear granulation is complicated by the interplay of granule nucleation, growth, and breakage and their non-linear dependence on liquid binder addition rate and granulation time. In an earlier paper, we demonstrated that during extended wet massing times, granule growth and breakage rates become equal (pseudo-steady-state granulation), and the ultimate granule size distribution depends only on agitation intensity and granulating fluid level. This significantly simplifies scale-up. The granule size distributions produced in these long granulation times were quite narrow compared to those produced in more typical granulation times.This work provides additional characterization of the granules produced in “steady-state” granulation. We observe an interesting microstructural change in granules comprised of microcrystalline cellulose and lactose. During extended wet massing, these granules evolve from typical agglomerates comprised of primary MCC and lactose particles to a bi-continuous structure with a skeleton of porous cellulose with pores filled with the remaining formulation components. The soluble components can be removed from the pores by dissolution, leaving the porous MCC skeleton. The dependence of the microstructure on wet massing time, liquid level, and MCC content is reported.