Granulation with Dow Cellulosic Polymers II. High Shear Granulation

The data for METHOCEL K3P LV
and the two viscosity grades of PVP
at 3%w/w binder are presented in
Figure 33, which illustrates the
unimportance of the method in which
the binder was added. The dissolution
of tablets containing PVP (K90) was
about 6 minutes slower than those
prepared with the METHOCEL
cellulose ether, which was in turn
about 3-4 minutes slower than that of
tablets prepared with PVP (K29-32).
The same general trends were
evident at the 6% binder level, where
the t 80% values were approximately
15 minutes, 19 minutes, and 29
minutes for PVP (K29-32),
METHOCEL K3P LV, and PVP
(K90), respectively.
The final figure, Figure 34, compares
the performance of METHOCEL
K3P LV and acacia at 6% with that of
the pregelatinized starch at the 10%
level. (Recall that the acacia and
pregelatinized starch were only
utilized in the solution binder addition
method.) The acacia tablets dissolved
relatively rapidly, while the profile of
tablets prepared with the modified
starch was virtually indistinguishable
from that of tablets made with
METHOCEL K3P LV.
20 High Shear Granulation: Vitamin C Model
Conclusions: Vitamin C Model
Formulation
The METHOCEL and HPC polymers
formed good granules with good
milling properties, both when added
as aqueous solutions to the high
shear mixer-granulator, or added as
a dry powder to the unit followed by
granulation with water. Good
densities, comparable with the
competitive binders, were obtained
with both binder addition methods.
The particle size distributions
appeared to be completely
satisfactory. The majority of the
granules were retained on the 20,
40, and 60 mesh screens; less than
20% of the material was finer than
140 mesh (with the exception of
PVP (K90).
Increasing the amount of binder in
the granulations caused an increase
in hardness in 72% of the cases
studied, caused a decrease in 11%,
and caused no change in 17%. At the
3% level, most of the binders gave no
difference in hardness as a function
of binder addition method, whereas at
the 6% level there generally was a
difference, but there was no
consistency in which method gave
the harder tablets. The binders that
consistently gave the hardest tablets
were HPC-LF, HPC-EF, and PVP
(K90). The binders that routinely gave
the least friable tablets were
METHOCEL E15P LV, HPC-LF, and
METHOCEL A15P LV. Povidone
(K29-32) gave tablets that were
relatively soft and friable.
Comparing the cellulosic binders at
the 3% level shows very little
difference in the dissolution
performance between METHOCEL
K3P LV, F4P LV, E5P LV, and both of
the HPC products. METHOCEL E15P
LV produced tablets with a slightly
longer dissolution profile, while the
profile for tablets utilizing METHOCEL
A15P LV was somewhat longer yet.
At the 6% binder level, METHOCEL
K3P LV, F4P LV, and E5P LV are
recommended; the HPC products and
METHOCEL E15P LV gave t 80% of
about 30 minutes. The methylcellulose
product produced tablets with
dissolution times of over 1 hour.
There were only minor differences
resulting from the dry and solution
binder addition methods. The PVP
(K29-32) and acacia gave tablets with
the most rapid dissolution, but the
tablets prepared from both were
relatively soft and friable. Tablets
containing a pregelatinized starch
used at the 10% level had essentially
the same dissolution behavior as
tablets containing METHOCEL
K3P LV at 6%.