gaining popularity in the industry.
High shear wet granulation is a cornerstone of the formulator’s and process engineer’s pharmaceutical manufacturing toolbox. It is used to increase the density and particle size of a composition to improve
powder flow and compressibility on the tablet press when dry
processing methods are insufficient to produce tablets or capsules with acceptable uniformity, hardness, and friability.
Although the general principles of granulation technology
have remained unchanged for several decades, the emergence
of several process modifications seem to be gaining popularity
among the pharmaceutical industry. Two of those modifications
are wet milling operation and spraying in a controlled manner
using a spray nozzle over an extended period of time.
Wet milling is typically done by positioning a particle size
reduction milling machine at the discharge of the high shear
granulator. After granulation, the material is discharged
through the milling equipment and can be either vacuumed
into the bowl or into the drying equipment. The mill is
equipped with a screen specially designed for wet milling
with larger openings than typically used for final particle
sizing. This allows the material to pass through the mill
without causing material buildup and equipment blockage.
Different categories of milling equipment can be used to successfully wet mill granulation. The impact mill and screening
mill are two of the most popular. As the names may indicate,
the impact mill imparts more energy on the granules, while the
screening mill is gentler on the granules. Each type has its own
place in pharmaceutical processing and needs to be carefully
evaluated when developing a process for a new product.
Wet milling provides several processing advantages. Larger
and lumps are reduced
into smaller particles
that are more uniform
in size. This unifor-
mity impacts the dry-
ing mechanism and
therefore the drying
efficiency. In order for
moisture to dry from
a particle, two things
need to occur. First,
the moisture needs to
diffuse from the inner
part of the granule to
the surface. Second,
heat transfer at the surface causes the moisture to evaporate.
Drying can only progress at a rate that equals the slower of
these two items. Wet milling increases drying efficiency by
reducing the particle size distribution, minimizing the distance
moisture needs to diffuse, and increasing the surface area for
The elimination of large particles and lumps also prevents
case hardening, an undesirable condition where the mass on
the outside of a particle dries faster than the inside and cre-
ates a barrier that seals moisture in the particle core. Case
hardening makes it difficult to reach a consistent drying
endpoint and often causes problems with downstream pro-
cessing due to moisture and content uniformity problems.
Wet milling also allows the granulation endpoint to be
pushed to a more aggressive level. Traditional granulations that
would be considered “over granulated” often work well and produce very acceptable results when wet milling is utilized. This
is because the large, dense lumps of material are broken back
down into particles that can be handled and dried.
Finally, because wet milling imparts a particle sizing step
earlier in the process, final particle sizing after drying does not
need to be as aggressive. The result is particle size distribution
that is more uniform, further improving material powder flow.
UNIFORM EXTENDED SPRAY TIME
Although there are still processes that utilize the ladling or
pouring methods of granulating liquid addition, most current
high shear granulating equipment comes equipped with spray
nozzle technology for liquid distribution. While the older
“dump and mix” school of thought often works well in many
situations, there is generally little downside to using a spray
nozzle for liquid addition. Also, while rapid liquid addition
might work at a lab scale with small quantities, at a larger
scale more issues may be encountered when mass effects
have a greater impact. The upside of using a spray nozzle is
a more controllable liquid feed rate and more uniform distribution. Not only do spray nozzles take operator variability
out of the granulating process, they also allow for a significantly extended spray time at a controlled addition rate.
Traditional high shear granulating has three phases: dry
mix, liquid addition, and wet massing. The dry mix ensures a
uniform dry powder composition and lasts for about 2 – 5 minutes. The liquid addition adds the granulating liquid in about
1 – 10 minutes. Once the liquid has been added, the wet mass-
ing phase ensures uniformity and imparts mechanical energy
to form a strong granule formation. This phase can last from
about 2 minutes until a granulation end point is achieved.
Certain products have been demonstrated to benefit from
High Shear Granulating
A look at advances in wet milling and controlled spraying in granulation operations
■ By Raja Krishnan and Michael Buzecky, Fluid Air, Inc.
■ 28 SEPTEMBER 2013 | PHARMACEUTICAL PROCESSING
■ PHARMPRO. COM