Granulation with Dow Cellulosic Polymers II. High Shear Granulation

solution viscosity) can be an
important variable in the effectiveness
of a binder. The effect of molecular
weight will be addressed in
subsequent studies.
The METHOCEL polymers used
included: METHOCEL A15P LV
(15 cps methylcellulose USP);
METHOCEL E5P LV and E15P LV
(5 and 15 cps hypromellose, USP
substitution type 2910); METHOCEL
K3P LV (3 cps hypromellose, USP
substitution type 2208); and
METHOCEL F4P LV (hypromellose
USP substitution type 2906). The
METHOCEL polymer is in many ways
similar to the material identified as
METHOCEL F4P LV in Part I, Fluid
Bed Granulation. By the USP
monographs, MC and hypromellose
viscosities are reported as those
obtained from 2% aqueous solutions,
measured in a Ubbelohde (capillary)
viscometer at 20°C.
The HPC polymers utilized were the
HPC-EF and HPC-LF grades. HPC-
EF has a viscosity of 250-750 cps,
measured as the viscosity of a 10%
aqueous solution at 20°C with a
Brookfield viscometer, using the #2
spindle at 30 rpm. The viscosity of
HPC-LF is 75-150 cps, measured as
a 5% aqueous solution at 20°C, again
using the Brookfield viscometer, #2
spindle, and 30 rpm.
2 High Shear Granulation: Acetaminophen Model
The povidones used in this study
were USP grades of the K29-32 and
K90 types.
Acacia (gum arabic, spray dried
SDGA/1) was obtained from AEP
Colloids, Inc. The spray dried form is
white to very pale yellow and is in
compacted fragments or whole
spheres. One gram dissolves in 2 ml.
of water, forming a solution which
flows readily and is acidic to litmus.
A pregelatinized starch having a coldwater
soluble fraction of 10 to 20%
was included in the study. This type of
starch is a combination of
approximately 5% amylose, 15%
amylopectin, and 80% unmodified
corn starch, with at least 90% of the
particle weight less than U.S. sieve
size 100.
In all cases except the pregelatinized
starch and the acacia, the binder was
added both as an aqueous solution
and in the dry state (in which the
granulating liquid was simply water).
The powders were charged into the
granulator and premixed for 60
seconds at high chopper speed and
200 rpm main impeller setting to
delump and homogeneously mix the
contents. The binder solution or
simply water was added to the
granulation while the Fugi was
operated at high chopper speed and
200 main impeller speed until a
proper wet mass was achieved. The
resultant wet mass was passed
through a CoMil (Quadro, Inc.)
equipped with a square hole screen
(2A-3750037/63), impeller (2A-1606-
086L) operating at a speed of 2665
rpm. The milled material was placed
on trays and oven dried at 110°F to a
final moisture endpoint of 1-2%. The
moisture analysis was performed on
a Mettler Infrared Drying Unit LP16-M
(Mettler, Inc.). Upon drying, the
granulation was dry sized via the
same CoMil operating at the same
speed setting and equipped with a
round hole grater-type screen
(2A 079G031/23120) and impeller
(2A-1601-173). After dry sizing, the
granulation was placed in a V-blender,
where the lactose and disintegrant
were added and mixed for 10
minutes. Finally, the lubricant was
added, and following an additional 2
minutes of mixing, the final mixture
was compressed at 1000, 2000, and
3000 lbs. total compression force on
an instrumented rotary tablet press.