Granulation with Dow Cellulosic Polymers II. High Shear Granulation

Conclusions; Methazolamide
Model Formulation
In terms of densities and
compressibility indices, there were no
real differences in the polymers
evaluated here. The particle size
distributions were all reasonable, but
several of the binders exhibited the
behavior where more fines were
present at the higher binder level than
at the lower; METHOCEL K3P LV
and the HPC products were
exceptions to this observation. For the
cellulose ether materials, the tablets
produced from this formulation were
slightly softer than those produced
from the Vitamin C and significantly
softer than the acetaminophen
formulations, granulated in a high
shear mixer-granulator. In particular,
however, METHOCEL K3P LV and
the PVP polymers were more
effective binders with respect to tablet
hardness in the methazolamide
formula. Comparing identical
methazolamide formulations
granulated by fluid bed and by high
shear reveals that the use of
cellulosic polymers in the fluid bed
produces significantly harder tablets.
Even though the tablets were slightly
softer, the friabilities were still quite
low. Friabilities were comparable to
the acetaminophen high shear work,
lower than the Vitamin C high shear
work, and comparable with the
methazolamide fluid bed work. The
binders that were best overall
considering both hardness and
friability were 3% and 6%
26 High Shear Granulation: Methazolamide Model
METHOCEL K3P LV, 6% HPC-EF,
and the povidones. Considering the
dissolution characteristics of the
cellulose ether materials, all gave
t 75% of < 20 minutes when used at
the 3% level, with METHOCEL A15P
LV being just slightly the fastest.
Consistent with the other model
systems, increasing the binder level
resulted in longer dissolution times. At
6%, METHOCEL A15P LV was the
fastest, with METHOCEL E15P LV,
E5P LV, and F4P LV at t 75% of 25
minutes, K3P LV at 30 minutes, HPC-
EF at 37 minutes, and HPC-LF at >
45 minutes. Considerable differences
were evident with the two viscosity
grades of PVP. While the K29-32
grade gave rapid release at the 3%
level, the K90 grade produced the
longest dissolution time of any of the
tested binders at the lower binder use
level. At 6%, the K90 grade produced
tablets having t 75% > 45 minutes. All
factors considered, the best binders
for this formulation were METHOCEL
K3P LV at 3%, PVP (K29-32),
METHOCEL A15P LV, and the HPC
products at 3%.