DEM simulation of continuous tablet coating: Effects of tablet shape and fill level on inter-tablet coating variability

摘要

Tablet coating is a common pharmaceutical technique of applying a thin polymer-based film to a tablet or a granule containing active pharmaceutical ingredients (APIs). Inter- and intra-tablet variability of film coating is a critical issue in the production of solid oral dosage forms. In fact, inhomogeneity in the coating thickness can lead to significant variations in the delivery rate of active pharmaceutical ingredients and compromise the functional attributes of the tablet film. Although attempts have been made to use numerical approaches to analyze this complex problem, at present the uniformity of coating thickness is difficult to predict without expensive experimental work.The aim of this work is to analyze and understand the effects of tablet form and fill volume on the intra-tablet coating variability in a semi-continuous coating device. To this end, the Discrete Element Method was used to numerically reproduce the tablet motion inside a chamber of the coating pan. First, the material attributes of a sample placebo tablet were experimentally quantified in detail. Thereafter, three different tablet shapes, namely bi-convex, oval, and round, were modeled by means of the "glued spheres" method. The effect of three different fill volumes was then analyzed in terms of RT of the tablets under the coating spray, leading to a quantification of the intra-tablet coating variability for each particle shape. A detailed analysis of the tablets' velocities, both translational and rotational, on top of the tablet bed is presented. These results help to understand the dynamical behavior of the tablets under a spray gun that is essential for a satisfactory intra-tablet coating homogeneity. Finally, the various behaviors observed during the numerical simulations were addressed through a detailed analysis of the tablets' flow on the bed in terms of mean velocities and granular temperatures. The aim of this work is to demonstrate how a numerical simulation may be used for the development and design of continuous pharmaceutical tablet coating processes.