Tuesday, May 19, 2009

tablet press operation

Sticking occurs when granules attach themselves to the faces of
tablet press punches. Picking is a more specific term that
describes product sticking only within the letters, logos, or
designs on the punch faces. This article explains the causes of
sticking and picking and describes the steps you can take to
resolve both problems.
hen a product begins sticking to the punch face, the
blame game starts. Unchecked, the finger-pointing can
zoom around to encompass every person with a hand in
the tablet-making process. No one wants to bear the
responsibility for the problem.
From your colleagues in R&D you hear, “It didn’t stick
to the punches in our single-station lab press. Check with
the tablet press operators. They’re not running the tablet
press correctly.” When you check with the tablet press
operators, they say it’s a granulation problem. “If the
product had been granulated correctly we wouldn’t have
sticking problems.” The people in quality assurance point
out that the product is sticking to the tooling. They suggest
that you look for worn tooling or tooling that needs
to be polished. Or maybe the tools weren’t made correctly
to start with. “Call the tooling vendor,” they say.
And so it goes.
Is the problem coming from the tablet press or the
product formula? Is it the tooling or is it the granulating
and drying process? Is it the operators? No one knows for
Sticking and picking
Sticking is one of the most common problems of
tablet making. It occurs when granules attach and stick to
the faces of the punches instead of locking together to
create a uniform tablet. The photos above show examples
of tablets rejected because of sticking. Figure 1 shows the
face of an upper punch with sticking product. Picking is a
specific type of sticking in which particles stick within
the letters and logos that are embossed or debossed on
the faces of the compression tooling. See Figure 2.
Regardless whether it’s sticking or picking, the result is
a defective tablet. To salvage the batch, you may have to
visually inspect the tablets. This certainly will slow production
and decrease yields, but there is no alternative.
The formulation is completed; you can’t send it back
down the hallway for reprocessing.
Sticking can happen at any time throughout a batch. It
occurs most often at the initial setup of the tablet press,
but it might just as easily appear randomly in a production
run. It might also appear at regular, predictable times.
With some products,
sticking is so
predictable that
operators consider
it a success when
they can run for 2
hours without any
Knowing the
moisture content,
particle size distribution,
and other
product properties will help you predict whether a product
will compress without sticking. However, even products
that meet your specifications may stick and pick.
The fact is, you may not know how well a product will
compress until it is on the tablet press.
This article will offer some strategies to identify the
causes of and solutions to sticking and picking. The
source of the problem may relate to the product, the tooling,
the upstream processes, or the operation of the tablet
press. It might also be a combination of these factors.
Sticky granules make good tablets...right?
When a tablet press is set up for the first production
run, the operator will first adjust the weight cams to get
the correct tablet weights. (Actually, you adjust the position
of the lower punch in the die. In doing so, you control
the volume of the die cavity. At a given bulk density,
the die volume will correspond directly to tablet weight.)
Once you have the weights right, you adjust to attain
the proper tablet thickness. Tablet hardness is determined
by a combination of variables, including tablet weight,
tablet thickness, press speed, and the dwell time of the
upper punch in the die at full compression force.
Products with granules that are super-sensitive to compression
—call them sticky granules—can form excellent
tablets. But they are also prone to sticking to the punch
faces. If this is the problem on your press, you are likely
to see the problem worsen over the course of the production
run. That’s because granules super-sensitive to compression
will readily compact as they flow through the
hopper and into the feed frame.
If a powder compacts before it reaches the die cavity,
the bulk density of the formulation increases, impeding
your ability to control the tablet weights. As the weight
of the tablets fluctuates, so does the compressive force.
This variation in force, in turn, can exacerbate the product’s
tendency to stick. That starts a downward trend, and
that’s why the sticking gets worse and worse.
Experienced tablet press operators know a trick about
compression: If sticking is a problem, they quickly overcompress
the product and make very hard tablets for a few
press revolutions. This quick action, known as “shocking
the press” can work very well. Why? The answer is fairly
simple: The stronger compaction forces cause the granules
to bind with the tablet and pull the stuck granules away
from the punch face. But be careful when using this method
to shock the press. If you overload the punches, you will
damage them or even break them.
Experienced operators can also “save” a sticking batch
when inexperienced operators don’t know where to start.
Experienced operators, for example, often hear changes
in the sound of the press and know that the product is
sticking. Their first action might be to change the compression
settings, such as by increasing the force, reducing
tablet thickness, or decreasing pre-compression thickness.
They may even slow the press. A good operator
always pays attention to the tablet and the tablet press.
The sooner you identify a sticking problem, the faster
you can resolve it.
The p’s and q’s of tooling
Sticking and picking are usually the result of many factors,
but because they happen on the face of the punch,
it’s easy to blame the tooling. And sometimes the blame is
placed there correctly, especially in the case of picking.
Picking occurs on the letters, logos, and other designs
of the punch face. Usually you’ll find the picking within
the “closed” numbers and letters that form “islands.”
These numbers are 0, 4, 6, 8, and 9. Some of the letters
are A, a, B, b, D, d, e, P, p, Q, q, and so on. See Figure 2.
Tooling manufacturers know about these problematic
numbers and letters and do a good job of making punch
faces that prevent picking. You can even order tooling
with a “pre-pick” feature. A pre-pick feature means that
the punch face has islands that are not as deep as the rest
of the embossing. Despite the shallower islands, the
punch still makes a clean, legible indentation. Another
strategy is to change the height and angle of the embossing.
Doing so produces a tablet with the same appearance
but without the picking problem.
Note that tablets destined to receive a coating will have
lettering that is less severely angled, wider, and shallower
than the lettering on non-coated tablets. Thus the design
of coated tablets helps reduce sticking and picking.
The choice of steel and the degree of polish on the
punch will also affect picking. Type D2 and Type 440C
steel contain more chromium than other steels, which
Figure 1
Product sticking to the face of an
upper punch
Figure 2
An example of picking
Lower punch
The “islands” formed
by “closed” letters
and numbers are
prone to picking.
reduces sticking and picking. High-chrome steels also
allow you to achieve a mirror-like polish. Another option
is to specify a chrome-plated finish for a hard-faced,
wear-resistant surface. However, if the product is abrasive,
the chrome-plated finish can wear away quickly. Ask
your tooling supplier about these options.
In some cases, changing the tool design and its surface
finish is enough to stop sticking and picking. But changing
designs could well be a waste of time and money,
because many products will stick and pick no matter what
changes are made to the punch design.
Air entrapment. The act of compression can trap air in
the concave cup of the punch face. The deeper the cup,
the more likely it is to trap air. This trapped air creates a
soft area on the very top of the tablet. In such cases, the
granules don’t know whether to stick to each other or to
stick within the punch cup. It is similar to making a tablet
that is too soft: The granules aren’t sure where or what to
stick to.
The solution here is to make certain the punch dwell
time is correct and that air evacuation is adequate. The
primary way to reduce entrapped air is to increase the
force of the pre-compression stage so that there is less air
to evacuate during final compression. You should also be
certain that the tablet is compressed as high in the die as
possible. This is referred to as the depth of upper punch
penetration. The higher it is within the die, the easier and
faster the air can escape during compression.
If those adjustments are not possible, consider using
tapered dies to help get the air out. Talk with your tooling
manufacturer. Tooling manufacturers are specialists
and they can probably help you solve the problem by
adding a taper.
Another possible solution is to specify a tablet shape
that uses a compound radius. Doing so “flattens” the very
top of the tablet, eliminating the air pocket. The change is
slight but effective. Furthermore, it will not cause a noticeable
change in the tablet shape
or design. See Figure 3.
You may discover that new
punches are more likely to
entrap air than used punches
simply because of their tighter
clearances. Tight clearances are
good, but they can cause air to
escape more slowly during
compression. With the old
tooling, air escapes more
quickly so particle-to-particle
bonding is more likely. When
customers tell me that brand
new tooling gives them more
hardness, sticking, and capping
problems than the old tooling,
I attribute the problems to the
tighter clearances of the new
tooling and a decrease in the
evacuation of air.
Lubricating the right way
The function of a lubricant in the product formulation
is to prevent powder from sticking to the punches, dies,
and other metal components of the tablet press. A lubricant
also facilitates the ejection of compacted tablets. It is
not a liquid or oil, but a light, fine powder. Typically,
lubricants account for a small percentage of the formula’s
content, from 0.25 percent to 2 percent. The most common
lubricant in pharmaceutical formulations is magnesium
Despite the small particle size and the small quantity
of the lubricants, they strongly affect your ability to make
a good tablet. If they are not blended correctly in the
mixture, they will not function as designed. There are
two common errors when processing lubricants. The first
error is neglecting to pre-screen the lubricants to remove
the lumpy, over-size particles. The second error is failing
to blend the lubricant evenly into the product formulation.
The lubricant must be able to contact the metal
parts to work correctly. However, it is better to underblend
the lubricant than to over-blend it. Over-blending
will hide the lubricant within the other particles, rendering
it useless.
If you run a press without lubricant, you may hear the
powder squeaking as it compresses. You will also notice
an increase in the force needed to eject the tablet. In fact,
the increase may be so great that it damages the punches
and the ejection cams. The absence of lubricant or the
presence of incorrectly blended lubricant will also lead to
If you don’t recognize that poor lubrication is causing
the sticking problem, you or your colleagues are likely to
blame the tooling. The next step in this misdiagnosis is to
stop the press, remove the stuck products, and polish the
punches before restarting the press. Because polishing the
punches can provide short-term relief from sticking, you
may repeat this cycle throughout the production campaign.
By the time you’re
done, you’ll have convinced
yourself and your team that
the tooling’s loss of polish is
the source of the problem.
But that is incorrect.
True, polishing the
punches can solve a sticking
or picking problem temporarily,
because many polishes act
as mold-release agents. So the
act of polishing did nothing
more than work this moldrelease
agent into the surface
of the punch. The satisfactory
—but temporary—result
is a successful production run.
Then the product begins to
stick again and you re-polish.
Sometimes polishing does no
Figure 3
Using a compound radius to “flatten” the tablet (B) can help
reduce sticking without noticeably changing the tablet shape.
good whatsoever. Other times you might go for an hour
or so before sticking resumes.
Some companies accept these short production runs as
part of doing business. They expect some products to
start OK, and then to stick eventually. They will remove
the punches and polish them throughout the run. But ask
your operator about the polishing routine. The secret
that every press operator knows is that some polishing
compound must remain on the punch tips for sticking to
stop. They know not to clean the punch tips with isopropyl
alcohol, as is standard. If they did, the sticking
would return immediately. So is polishing really solving
the problem? Not likely.
Even so, a combination of factors may convince you
that poorly polished punches are indeed the source of the
sticking. Recall that many sticking problems occur at
startup, when all the metal components are clean and free
of any lubricant. Thus, the punches are prone to sticking.
The reaction of most operators when they see sticking is
to stop the press, pull the punches, and polish again, even
though the punches were just polished.
While they polish the punches, operators might give
the press itself only a cursory cleaning. Excess powder is
removed, but a thin dusting of the product is left behind.
When the punches are re-installed, the press runs without
sticking. Thus the operators walk away believing that
polishing the punches solved the problem when the distribution
of the lubricant within the product was actually
the source of success.
To prevent sticking at startup, some companies routinely
distribute lubricant by hand before tabletting. This
puts a dusting on the press that prevents sticking at the
start. Excess lubricant is gone after the first few press revolutions.
Some people think this is unacceptable. But is it
any less acceptable than not cleaning the punches after
Process-related sticking
Some sticking and picking relates to upstream processing.
Improperly applying binders or poor drying of the
product, for example, can make polishing the punches an
hourly event at some companies.
Application of binder. During the granulation process,
a liquid binder is often added to a powder blend, thus
bonding (binding) the ingredients together to form granules.
Binders are often called pharmaceutical glue, and to
work as planned, the distribution must be even throughout
the batch of product and the binders must be uniformly
If binders are not distributed evenly and dried completely,
some portions of the blend will contain concentrations
of binder. In the drying process, these overly wet
granules become dry on the outside, but not on the
inside. This is called case-hardening.
Case-hardening can occur even when binder is added
correctly but drying was too rapid. Removing the moisture
too quickly causes some binder to move to the granule’s
exterior. This migration of binder to the granule surface
creates a hard shell around other material that may
not be completely or evenly dry. This phenomenon leads
to two possible causes of sticking: entrapped moisture
and concentrated binder on the granules’ surfaces.
Slowing the drying process will sometimes eliminate both
Changing the way you add binders or dry a granulation
is easier said than done. Nonetheless, scrutinize all the
steps of your methods to find and prevent problems. After
all, proper granulating is a fundamental issue when sticking
is the problem. Some of you may opt to polish the
punches again and again instead of addressing the true
cause. Or, sometimes a company buys new punches. The
new punches may work better than the old ones, but often
only because the new punches are very polished. As discussed
earlier, new punches may create a bigger problem
because their tighter clearances lead to air entrapment.
Milling. Many times mills are viewed as ancillary
pieces of equipment that you just roll into a vacant room
to perform a quick task. That attitude raises questions: Is
this milling step controlled and predictable? Will the
operators mill a batch on Monday at 8 a.m. the same way
they do on Friday at 4 p.m.?
Overly fine particles, known as fines, often exhibit
poor compression characteristics and may cause sticking.
The fines are usually the result of milling friable powders
incorrectly or at inconsistent feed rates. With too many
of these dust-like particles in the product formulation, it
won’t flow or compress well. The fines also create a dusty
atmosphere and cause tablet-to-tablet weight fluctuations.
Furthermore, fines can get trapped within the logos
and lettering on the punch face, especially if the punch
design was made to handle a different particle size range.
Non-friable powders can also cause problems.
Especially problematic are the powders that are readily
compressible, because they can compact during the
milling step. Furthermore, some products may re-agglomerate
if they are stored too long. In that case, they will
need to be de-agglomerated in a low-shear mill before
going any further in the process. Products that have reagglomerated
flow poorly and cause weight fluctuations
which, in turn, create hardness variations that increase
the potential for sticking and picking.
Pinning the problem on R&D
Why do products compress into a tablet well in the
lab but not on the production floor? We have all had this
question at some time. More accurately, you might think
that if only the product development team and the R&D
people had developed the product correctly, we wouldn’t
have sticking, picking, or other problems on the production
There may be some truth to such thinking, but you
should understand that identifying operational differences
between lab and production equipment is difficult,
especially when the product is still under development.
Because of scale-up problems, many companies use production-
capacity machines when developing products.
The substitution of critical ingredients during product
development can also hamper scale-up success.
Scale-up. Some machines scale up better than others,
and changing the batch size or a machine’s capacity may
or may not give your product its intended attributes.
Scale-up guidelines are general, and they don’t always
work. I’ve seen plants that use identical or comparable
processing machinery to make the same product, but the
properties of the products at each plant differ. You can
attribute these differences to environmental factors, the
skill of the people who work at the plant, or both. There
is still a lot of art in the science of tablet making.
Ingredient substitution. Many of the ingredients in
tablet formulations are expensive, especially in the pharmaceutical
industry. Therefore, sometimes a company
substitutes a cheap ingredient for an expensive one during
product development. Or the company may not have
enough of the active pharmaceutical ingredient to make
tablets and to perform all the developmental tests. In that
case, the company will again use a substitute.
If the substitute doesn’t have the exact attributes of the
true ingredient, then test results can lead you in the
wrong direction. Time and storage conditions may also
cause the ingredient to behave one way in the lab and
another way on the plant floor. This may include more
fines, de-mixing at the tablet press, and heat sensitivity,
all of which may cause sticking.
The one conclusion you should draw from this article
is that a sticking or picking problem can have one or several
causes. Polishing the punches during a production
run is a temporary fix, not a long-term solution.
Environmental factors can affect how well a tablet will
form. Some products are so sensitive to temperature and
humidity that they may compress differently or not at all
with the slightest change in the environment.
If you’re the troubleshooter in charge of solving a
sticking problem, evaluate the problem at the press and
work upstream from there. Study all the process variables
and record as much data as possible. Finally, if you make
a change, try to make just one change at a time. This will
help you link each change to a result. T&C

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