Modeling of growth kinetics of wet granulation in a high shear mixer by means of image processing and analysis

Abstract

Wet granulation is one of the most important operations where fine particles are agglomerated into larger granules by adding a binder. The process is used in many chemical industries including pharmaceutical, mineral processing, agricultural, and detergents. In spite of its importance and many years of research, the understanding of the granulation process is still quite limited. The main objective of this research is to study the effects of initial particle size distribution (PSD) shape (unimodal versus bimodal), initial particle size, and the amount and viscosity of binder on growth kinetics and the mechanism of wet granulation, and to model the agglomeration mechanism of particles, using the population balance equation (PBE) and considering the initial properties of binder and particles. This research was carried out in three different phases. Initially, an image processing and analysis algorithm was validated and used to determine the PSD during the wet granulation. The test of the vision system capability to determine particle size indicated high precision with a repeatability of 0.0012 in and 0.5% relative standard deviation. Near-infrared (NIR) spectroscopy method was validated and used, at the same time, to determine the moisture content. In the second phase, several variables were investigated. The Split-Plot experimental design with three factors (amount, viscosity of binder, and initial PSD) and three levels for each factor was carried out. The variation of these three factors are consistent with the viscous Stokes’ ( Stv ) number developed by Ennis et al. [1991]. The effect of initial PSD shape, unimodal versus bimodal, on the growth kinetics and mechanism of wet granulation were also evaluated. Wet granulation of pharmaceutical powders with initial bimodal PSD presented growth kinetics in two stages. The first stage of granule growth is fast, similar to a non-inertial regime found by Adetayo et al. [1995]. This stage is controlled by binder amount and the high probability of coalescence because of collisions of small and large particles that increase the growth rate, as indicated by coalescence kernels published in the literature. The second stage is characterized by slow agglomeration of particles with a water content 13.6% v/w, and slow breakage of particles with water contents of 9.9 and 11.7% v/w. In contrast, wet granulation of pharmaceutical powders with initial unimodal PSD exhibited slow growth kinetics consisting of one stage because high concentration of particles of similar size decreases the probability of granule coalescence, as compared to the high coalescence probability between collisions of small and large particles. In the last phase, an agglomeration model between small and large particles was developed based on diffusion of small particles to a larger one through binder layer on the particle surface. Furthermore, coalescence kernels with physical interpretation have been developed for each stage of wet granulation. The coalescence kernel of slow growth rate accurately describes the PSD during wet granulation process.