The development of a novel formulation map for the optimization of high shear wet granulation

Abstract

With a view to describing the powder agglomeration process, particles have often been considered as inert material and the solid–liquid interactions have rarely been contemplated. The present research aims to fill the gap in understanding how the nucleation and the early stage of the granule growth depend on some important formulation properties. The glass transition concept coupled with on-line impeller torque monitoring and measurements of the time evolution of the particle size distribution was used to give a description of the early stage of the agglomeration process in high shear wet granulation. A mixture of commonly-used pharmaceutical powders, which are amorphous and crystalline in nature, was processed. Accordingly, a new formulation map is presented which describes the onset of significant granule growth as a function of the key formulation components (i.e. diluent, dry and liquid binder). From this map, the minimum amount of liquid binder required to induce appreciable granule growth is determined as a function of the type, quantity, hygroscopicity and particle size distribution of the diluent and the solid binder. This map can be obtained from a priori glass transition measurement using a static humidity conditioning system and by fitting the experimentally obtained data using a modified Gordon–Taylor equation.