Granulation with Dow Cellulosic Polymers II. High Shear Granulation

Model Formulation
2: Vitamin C
Composition and Preparation
In this section of the study, the
following formulations were used:
75% Vitamin C
19.5% Lactose
3.0% Binder
2.0% Disintegrant
0.5% Lubricant
75% Vitamin C
16.5% Lactose
6.0% Binder
2.0% Disintegrant
0.5% Lubricant
Note that these formulations are
identical with those used in the earlier
fluid bed study. The formulation at 6%
binder is identical with the
acetaminophen model presented in
the previous section except for the
active ingredient; this will facilitate
comparisons on the effects of the
drug on the relative performance of
the various binders. Here, Roche fine
powder was utilized; all of the
remaining components were the
same as described on page 1.
The same binders were evaluated as
described on pages 1 and 2. The
processing of the Vitamin C
formulations was different from that
used in the acetaminophen
formulations. In this case, the active
and the lactose (and the binder in
those experiments where the binder
was not placed in solution) were
placed in the Fuji and mixed for 60
seconds at 200 rpm, chopper speed
high. The granulating liquid was then
added by means of the attached
funnel, and mixing was continued at
200 rpm, chopper speed high until a
proper wet mass was achieved. The
resultant wet mass was discharged
12 High Shear Granulation: Vitamin C Model
and wet milled in a CoMil (model
197S) using a square hole screen
(2A-3750037/63) and an impeller
(2A-1607-086L) at 2665 rpm. This
combination of screen and impeller
worked very well for wet milling for all
binders with the exception of PVP
(K90), which had very poor wet
milling properties. After tray drying at
110°F overnight to a moisture content
of < 1%, the granulations were then
dry milled with the CoMil using a
round hole grater-type screen
(2A-079G031/23120) and impeller
(2A-1601-173), again at 2665 rpm.
The disintegrant and lubricant were
added to the Vitamin C granulations
in a twin shelled blender and mixed
for 2 minutes. The complete mixtures
then were compressed at 1000,
2000, and 3000 lbs. total
compression force.
Properties of the Granulation
The apparent and tap densities and
the compressibility indices I of the
Vitamin C granulations were
determined using the procedures
described on page 3, and are given
in Tables 5 and 6. As in Tables 1 and
2, the apparent and tapped densities
are in g/cm 3 .
In this model system using the Fuji
VG-25P, the densities increased as
the binder level was increased from
3% to 6%. For the granulations
produced with the METHOCEL and
the HPC products, the increase was
small. However, the PVP binders
(especially the K29-32 grade) showed
a slightly greater increase in density
with an increase in binder
concentration. Once again, this
behavior can be understood by
examining the particle size
distributions that are presented in the
figures that follow. Comparing the
results where the binder was
prehydrated with those where it was
not shows that in the large majority of
cases, higher densities were obtained
by the "dry" binder addition method;
there was no trend in the I values.
Finally, note that for the comparable
6% binder levels, the compressibility
indices for Vitamin C granulations are
smaller (i.e., indicative of better flow)
than those obtained for the
acetaminophen granulations. It was
observed during tablet compression
that the Vitamin C granulations had
very good flow behavior.
Particle size distributions (PSD),
determined as described on page 4,
are given in Figures 19-27. The
figures show results for both of the
binder addition methods. Figure 19
compares granule sizes with 3% and
6% METHOCEL A15P LV. Increasing
the amount of binder gives small
increases in the quantity of material
≤ 60 mesh, but a decrease in the
amount of 40 mesh material. The 6%
binder level (solution) gave the finest
overall PSD. Granulation with
METHOCEL E5P LV (Figure 20)
shows a PSD that is typical of
virtually all of the other binders
tested. Increasing the amount of
binder gave an increase in granules
on 20 mesh, little change at 40 mesh
and < 140 mesh, and small
decreases in all other fractions. The
amount of material 80-140 mesh is
quite small. For the most part, the
binder addition method had relatively
little effect on the PSD at both the 3%
and 6% levels. This general pattern
was true for METHOCEL E15P LV,
METHOCEL F4P LV, METHOCEL
K3P LV (Figure 21), HPC-EF, HPC-
LF (Figure 22), and PVP (K29-32).
In Figure 23, it is seen that the PVP
(K90) granulations of Vitamin C
followed a somewhat different pattern
than the other binders just described.
With this binder, there was less
material on the 40 mesh screen,
somewhat more material on 80 mesh,