Effect of operating conditions and physico-chemical properties on the wet granulation kinetics in high shear mixer

The wet granulation process is sensitive to changes in product properties and process variables. The optimal process and formulation are based on the knowledge of the granule growth mechanisms and of the effects of product properties and process variables. This paper presents the study of wet granulation of microcrystalline cellulose powder, MCC (Avicel PH101) using high-shear mixer granulator. It aims at understanding the effect of operating parameters (impeller rotational speed, liquid binder flow ate) and of physicochemical properties (viscosity. wettability) of a binder solution on solid particles surfaces, on the agglomeration kinetics. The experiments are carried out with water, aqueous solutions of sodium carboxymethyl cellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose or a non ionic surfactant oxo-C(10)C(6) at a critical micellar concentration. Concerning the process variables the experimental results show that an optimal interval of impeller speed operation exists ranging from 150 to 200 rpm for granule growth. Below. an uncontrollable agglomerate size and localised over-wetting occur, and above granule breakage occurs. Increasing the liquid binder flow rate reduces the extension of the non growth regime, but does not affect the granule mean size. The effect of the physicochemical properties is evaluated using a modified capillary viscous number, Ca', that we define as the ratio between the viscous forces (mu(L)U) and the work of adhesion W(a)=gamma(L)(1 + cos theta). For Ca'<1. the viscosity of the solution does not significantly affect the granulation process. The dominant forces in the granulation process are the interfacial forces since increasing the work of adhesion enhances the growth kinetics. For Ca'>1.6, the viscous forces predominate and control the granule growth. (C) 2008 Elsevier B.V. All rights reserved.