Granulation with Dow Cellulosic Polymers II. High Shear Granulation

The remaining figures in this section
are comparisons of METHOCEL
polymers with the HPC polymers,
with the PVP products, and with
acacia and pregelatinized starch.
Figure 14 illustrates that using the dry
addition method at 3% results in
virtually no difference between the
two viscosity grades of HPC, both
having 80% drug dissolution in 25
minutes. If the same binders at the
same level utilized the "solution"
method, the HPC-LF gave the same
release profile, while the HPC-EF
gave a slightly longer (t 80% of 31
minutes) profile. Turning to the 6%
level, Figure 15 shows the results of
the solution method, with the HPC-EF
and HPC-LF curves indistinguishable
and with the time for 80% release at
the USP limit. Using the dry addition
method was not different in terms of
the release profile for HPC-LF, but
once again the EF grade had a
slightly longer release with t 80% ≈
32 minutes.
Figures 16 and 17 compare two
METHOCEL products with
polyvinylpyrrolidone. The dry method
at 3% (Fig. 16) shows that
METHOCEL E5P LV and PVP
(K29-32) are equivalent in dissolution
behavior, with the K90 grade just
slightly longer but well within the
specified time period. The solution
addition method gave results
essentially the same. Turning to the
6% level (Fig. 17), METHOCEL A15P
LV and PVP (K29-32) are practically
equivalent, with the K90 polymer
again slightly longer, now just within
the specification. Using the dry
method at the 6% binder level
produced dissolution curves where
the METHOCEL A15P LV was just
slightly longer than the PVP (K90)
and which was at the 30 minute limit.
Lastly, a comparison of acacia, a
pregelatinized starch, and
METHOCEL A15P LV is illustrated in
Figure 18. Here it appears that the
derivatized starch is also acting as a
disintegrant, giving the fastest drug
release of all the binders evaluated.
Acacia, despite giving quite soft and
very friable tablets, nevertheless gave
a somewhat unexpectedly long time
for drug dissolution.
Conclusions: Acetaminophen
Model Formulation
Granulations with acceptable
densities and particle size
distributions were obtained when 2
acetaminophen formulations having
3% and 6% binder levels were
prepared in a high shear mixergranulator.
There were only minor
differences in these properties
between granulations prepared by
adding the binder as an aqueous
solution or by adding the binder in a
dry state to the active followed by
granulation with water. The cellulosic
polymers (METHOCEL and HPC
products) tended to give granulations
with a higher proportion of granules
of 20-60 mesh, whereas the PVP
binders produced somewhat more
material in the 80-140 mesh region.
With the given milling conditions,
about 10% fines (