Uniformity of film-coating thickness is an important tablet quality attribute for a number of reasons. Poor uniformity or
significant variability in film-coating thickness, can lead to a range of issues, depending on the purpose of the coating.
In the case of coatings containing an active pharmaceutical ingredient (API), variability in potency between tablets arises
directly from coating variability. For a functional coating governing the drug-release profile, variability in thickness can
lead to variable drug-release profiles. Finally, high levels of variability for cosmetic coatings results in longer process
times to ensure that all tablets have received a sufficient amount of coating.
In practice, obtaining uniform coating depends on good mixing of the tablets in the coating pan and a uniform distribution
of tablet orientations in the spray zone to ensure uniform exposure of all sides of each tablet to the coating spray. The
tablet-flow dynamics are governed by several factors, including the equipment geometry, the presence of any mixing elements
(e.g., baffles), the conditions under which the equipment is operated, and the properties of the tablet cores, including size
and shape. To fully explore the effects of each of these factors on film-coating uniformity necessitates a large number of
physical experiments. Developing a model to study these effects in silico offers great savings in time, material, and labor costs.
DEM models are capable of accurately reproducing particle behavior in a number of pharmaceutical manufacturing processes and
are growing in use throughout the industry (5). During the past few years, Pfizer has developed DEM models of various processes
involving solid dosage forms using EDEM, a commercial DEM software package. Previous reports in the literature on film coating
uniformity are limited to spherical, standard round convex (SRC), or oval tablet shapes, and are often focused on operating
conditions rather than tablet shape (6–8). The computational approach reported here predicts both intertablet (i.e., uniformity
between tablets) and intratablet (i.e., uniformity between surfaces of a given tablet) coating uniformity and allows for the
study of many tablet shapes, including less common almond or bullet tablet shapes, permitting rapid screening of tablet shapes
and operating conditions that ensure quality of tablet coating uniformity.
To investigate intertablet coating uniformity, EDEM simulations of the operation of pan coaters were carried out at various
batch sizes, pan speeds, and different tablet shapes. The results were analyzed to determine the distributions of the residence
time per pass through the spray zone for each tablet and the circulation time between successive appearances in the spray
zone (see Figure 2). For conditions in which these distributions are wide, poor intertablet coating uniformity usually results.
In a laboratory-scale coating pan, simulations predicted that the residence-time and circulation time variability both decrease
with faster pan speeds. The effect of pan loading is mixed—residence time variability decreases with increasing loads but
circulation time variability increases with increasing loads. The net effect in this case is an increase in variability for
larger pan loads. Thus, improved intertablet coating uniformity is expected for faster pan speeds and smaller batch sizes,
but consideration must also be given to maintaining reasonable process throughput, and the potential for increased tablet
attrition that may occur at fast pan speeds.
Figure 2 (Pfizer–DEM): Simulation image of bullet shaped tablets in a laboratory-scale film coating pan where intertablet
coating variability is shown by varying degrees of blue color on each tablet, indicating the total residence time in the spray
zone for a given tablet.