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					Reprinted From September 2004                                                                                www.tabletscapsules.com



                   tablet press operation
Preventing and fixing weight and                                                                 Michael D. Tousey
                                                                                                 DI Pharma Tech
hardness defects: Strategies for
production personnel




Tablet specifications are tight, and the list of possible defects is
long: Variable weight, sticking, picking, black spots, streaks,
capping, lamination, variable hardness, among others. This
article focuses on variations in tablet weight and tablet hard-
ness. It pinpoints the possible causes of these defects and offers
                                                                       E  very product behaves differently on a tablet press,
                                                                       even if it’s the same product run on a different day. The
                                                                       variation often stems from changes in the properties of
                                                                       the raw materials—active ingredients and excipients—
                                                                       from batch to batch. Naturally, the goal is to minimize
                                                                       these changes. Tablet press operators, however, don’t
advice on preventing and fixing the source of the problems. It         have any control over formulation and granulation. They
also discusses the problems of formulations with too many              have to work with what they’re given, and their employ-
                                                                       ers expect them to make good tablets day in, day out.
fines.
            Tablet weight: Sources of variation                                            Tablet press adjustments
   If you’re a tablet press operator, the exchange below               As the tablet press operator, your job is to make good
may have a familiar ring to it.                                     tablets, no matter how poorly the product works on the
   Tablet press operator: It says right here that if the operator   tablet press. Here are some things you can adjust on the
cannot maintain target weights within acceptable quality            tablet press to overcome weight variations. Refer to
limits that I must report to you, my supervisor. So what            Figure 1.
should I do?
   Supervisor: You’re the operator. How’d you do it last                                             Figure 1
time? It worked fine on the last batch, right?
   Operator: I didn’t do anything differently. It must be the                        An illustration of the compression cycle
product. So what do you want me do?                                                                   9                 10




                                                                                                                                    Courtesy of the American Pharmaceutical Association
   Supervisor: Let’s pull out the checklist and review the
options.
                                                                               6       7         8
   So the two of them scan the checklist on weight con-
trol, which tells them that tablet weights are mainly
affected by                                                              1                   2
   1. Product variation
   2. Machine condition
                                                                         3
   3. Tooling condition                                                                4
                                                                                                                                5

   4. Flow of powder on the machine
   Let’s look at each of these factors.                                      Direction of rotation
   Product variation. Sources of product variation
                                                                         1. Product in feeder
include inconsistent powder density and particle size dis-               2. Scraper
tribution. While you may think that density variations                   3. Fill cam (partial view)
originate with your colleagues in formulation and granu-                 4. Weight adjustment cam
lation, density can also change on the press, often                      5. Ejection cam
because of overfilling of the die and re-circulation of the              6. Fill position
powder on the tablet press. The particle size distribution               7. Weight adjustment position
                                                                         8. Pull-down position
can change when the product becomes “unblended” dur-
                                                                         9. Pre-compression
ing transfer or because of static electricity. It might also             10. Main compression
change because the product can’t withstand the handling
and the mechanical stress it undergoes before reaching
the tablet press.                                                       Head pressure. This factor is related to the amount of
   Machine condition. The problems caused by a tablet               product in the overhead feed system or hopper. The
press that is poorly prepared or operated are legion. Look          more product present, the greater the head pressure, and
at the die table. Have you inspected its runout? The up             vice versa. When the pressure varies, so does the weight
and down motion under load on a new die table should be             of the tablets.
within 0.003 inch of the setting. You must also ensure that             Hopper level. To keep the head pressure consistent,
the pressure rolls and cams are in very good condition.             you need to maintain the product in the hopper at a con-
   Tooling condition. There is quite a bit of information           sistent level. Maintaining the level within a narrow range
available on tooling, but in a discussion of weight varia-          will reduce the potential for weight changes. Every oper-
tion, the punch working length is the property that you             ator knows that tablets produced at the end of a run
must know. Working length is the key factor in how                  weigh less than those made at the start. That’s because
punches affect tablet weight. New tools are made to a               the hopper level (and thus head pressure) decreases dur-
tolerance of one-thousandth of an inch, which is equal to           ing the run. If you determine that variations in the hop-
the thickness of one page in this magazine. Make sure the           per level are linked to variations in tablet weight, you
length of each punch is correct and identical.                      must monitor the weights more often and adjust your
   Powder flow and feed-rates. Many of the defects                  equipment so the level is more consistent.
related to powder flow and feed-rates stem from the for-                Feeder clearance. Generally speaking, you should set
mulation you’re given, not the operation of the tablet              the clearance between the feeder and the die table
press. Since the focus of this article is resolving problems        according to the product’s particle size. The smaller the
at the tablet press, I won’t go into the many problems              particle size, the smaller the clearance between the feeder
that may be related to the granulation process or the for-          base and the die table, and vice versa. That’s the general
mulation itself except to say that too many fines is bad. I         rule, but there’s a big “if” involved here: If the powder is
address fines in more detail at the end of the article and          waxy or very moist, a feeder that is incorrectly set may
in the sidebar on page 42.                                          compact, or “pack” the powder on the die table. In such
cases, the only way                                          Figure 2                                           replace it as needed.
to determine the                                                                                                When the blade is
best setting is to               Removing the feeder from this tablet press reveals segregated powder,          in bad condition or
experiment with dif-           which ultimately leads to weight fluctuations. Running the feeder too fast is    set up incorrectly, it
ferent clearances.                                       one cause of segregation.                              won’t scrape the die
    Feeder speed.                                                                                               table clean, and
The feeder delivers                                                                                             you’ll have problems
powder from the                                                                                                 with weight control.
hopper to the die                                                                                                   Re-circulation.
table, and the rotat-                                                                                           After the scraper
ing paddles in the                                                                                              blade levels the
feeder are intended                                                                                             powder in the die, it
to match the pow-                                                                                               guides the excess
der flow rate to the                                                                                            powder into a re-
rotational speed of                                                                                             circulation channel.
the press. The                                                                                                  This allows the
feeder can also un-                                                                                             powder to travel on
mix blended pow-                                                                                                the turret until it
ders, and the pad-                                                                                              returns to the feeder.
dles can break                                                                                                  If the fill cam is set
friable granules and                                                                                            too deep, there may
compact highly                                                                                                  be “an excess of
moist powders. The                                                                                              excess” powder in
best strategy is to                                                                                             the re-circulation
run the feeder as                                                                                               channel. When that
slowly as possible while maintaining proper tablet                       happens, the powder will not flow well. It may even back
weight. Running the feeder too fast can also cause the                   up, spill, compact, or leak, all of which can reduce yield
product to segregate. See Figure 2.                                      and alter the characteristics of the re-circulated powder.
    Fill cam. The fill cam allows the die cavity to be over-             Poor re-circulation produces a powder that is over-
filled. The excess is then pushed up and out of the die                  worked, compacted, unmixed, or otherwise damaged.
when it reaches the weight adjustment cam so that the                       To see what’s happening on the press, use a strobe
scraper blade can remove the excess as the die passes by.                light. It lets you see how well the product flows, how well
Most modern tablet presses include a “pull-down” posi-                   the scraper blade works, and how well the die and
tion after the weight adjustment step. I discuss this fea-               punches are functioning. See Figure 3.
ture later in the arti-
cle. Thin tablets                                            Figure 3                                              More on weight
require a shallow fill                                                                                                 variation
cam, and thick                A strobe light can reveal how well a product flows, how well the scraper blade        Those are some
tablets need a deep                      works, and how well the die and punches are functioning.               of the machine-
fill cam. It’s typically                                                                                        related variables
necessary to overfill                                                                                           that can affect tablet
the cam by 10 to 30                                                                                             weight. But what if
percent to maintain                                                                                             the weight problem
consistent tablet                                                                                               is related to the
weights.                                                                                                        product, not the
    Scraper blade                                                                                               machine? In some
condition and ad-                                                                                               cases, you’ll be
justment.          The                                                                                          tempted to return
scraper blade is a                                                                                              the problematic
wear part. It’s worn                                                                                            product to the gran-
by die table rotation                                                                                           ulating department.
and product abra-                                                                                               More likely, you’ll
sion. The more                                                                                                  be asked to consult
abrasive the prod-                                                                                              your supervisor.
uct, the faster the                                                                                                 Operator: So are
scraper’s edge will                                                                                             you going to answer
wear. So inspect the                                                                                            my question? What
blade frequently and                                                                                            do I do?
    Supervisor: Hmm. Isn’t the next shift going to be here     to exhaust the other options. Changing the powder den-
soon? Just joking!                                             sity is likely impossible, unless it’s a machine-induced
    In the real world, we have to solve the problems, not      density problem, as described earlier.
pass them along to the next shift. The first point to             You can increase dwell time to increase hardness, but
remember: Change one (and only one!) variable at a             longer dwell times typically require you to slow the
time. The next step is to define the extent of the prob-       machine, and that’s not usually an option. Instead, I rec-
lem by checking the tablets closely. Is there a pattern to     ommend that you first decrease tablet thickness by adjust-
the weight variation among individual tablets? Is the          ing main compression. Or, if you are already at the target
variation consistent? Does it come and go? Is the trend        weight, then decrease the thickness and increase the pres-
toward overweight or underweight tablets or does it go         sure at pre-compression. If you make that change and
both ways?                                                     you’re still achieving your target weight—that is, the
    At some point you might think, “But I’ve got auto-         tablet hardness increases and decreases rapidly but the
matic weight control on my tablet press! Why is this           weights are consistent—then you have what is known as a
happening in the first place?” Well, you have to under-        dwell-sensitive granulation. Finally, as mentioned earlier,
stand that “automatic weight control” works by allowing        you must know that the tooling is in good condition. If
the tablet press to make weight adjustments based on           the diameter of the tooling head flat is inconsistent within
variations in compression force. When the compression          the set of punches, then hardness will be inconsistent.
force is below the limit, an electronic signal tells the          To summarize: If you have trouble controlling hard-
tablet press to fine-tune the weight adjustment cam to         ness, first check for consistent weights. If the weights are
increase the fill volume. When the compression force           consistent, then check the thickness. If the thickness is
increases, another signal tells the tablet press to fine-      consistent and on target, then reduce the thickness at
tune the weight cam to reduce the volume of fill. That’s       pre-compression. Only increase the weight or reduce
all weight control is, nothing more. In short, you must        machine speed when you have determined that there are
make incremental adjustments to the weight cam to              no other options.
attain accurate volumetric change, which—given a
known and fixed product density—relates precisely to                             A word on particle size
gravimetric change.                                                I’m often asked to define the optimum particle size
    If you’ve gotten this far and the tablet weights still     distribution for making the perfect tablet. That’s a tough
vary too much, look closely at how well the machine            question. A particle size distribution within the right
keeps the product in the die before it’s compressed into a     range produces a good-looking tablet, but the nature of
tablet. Light, fluffy powders may “splash” out of the die,     that distribution depends on the tablet size. If the pow-
or the centrifugal force of the rotating turret may cause      der contained only large particles, like granular sugar,
the powder to come out. Either way, the tablet will be         you’d be making a porous sugar cube. Conversely, if all
underweight. The best defense against splashing is to use      the particles were superfine, you’d have other problems
the “pull-down” feature offered on most tablet presses         with compression. We need a range of particle sizes that
nowadays. This feature pulls the lower cam down, allow-        is in harmony with the tablet size.
ing the column of powder to drop into the die after fill-          Generally speaking, the smaller the tablet, the smaller
ing , thus preventing under-filling. It can also prevent the   the particle size. Likewise, the bigger the tablet, the big-
powder from splashing.                                         ger the particle size. Particles smaller than 200 mesh (74
    Reducing machine speed is another good strategy.           microns) are generally a problem for compression.
Naturally, you’d prefer to move the powder through the         Particles larger than 18 mesh (1,000 microns) can cause
tablet press as fast as possible, but the formulation dic-     weight fluctuations and create a textured appearance.
tates the speed of the press. I know companies that pur-       This is true for the most common sizes of pharmaceutical
chased a new press hoping to make their tablets faster,        and health-supplement tablets. Tablet shape is also a con-
only to find that the formulation couldn’t match the per-      sideration. If the tablet has small sharp corners, then the
formance of the press. If you want good tablets instead        particles must be small enough to flow and fit into those
of just fast tablets, you can only run the press as fast as    tight corners. However, if you’re making a round or
the product will allow. I’ve never seen a formulation that     caplet-shaped tablet, larger particles work better.
could outrun the machine.                                          Disintegration and dissolution times are generally better
                                                               for tablets made with a fine dust-like powder than they are
              Variations in tablet hardness                    for tablets made with large-particle powders. Finding a
   Hardness variation is a defect, and hardness varies         happy medium—a formulation that disintegrates and dis-
according to how well you control tablet weight, pow-          solves well and that also compresses well—requires some
der density, dwell time, tablet thickness, and the working     true formulating skills. I think that formulators too often err
length of the tooling.                                         on the fine-particle side of the issue and don’t consider all
   Increasing the tablet weight can increase the tablet        the issues of tablet making. In short, fines affect yields,
hardness, but your supervisor may forbid that because it       punch lubrication, compressibility, and can cause the tablets
“just gives product away.” Instead, you’ll be encouraged       to cap, laminate, or show other defects. Fines also increase
My gripe with formulators and granulation staff: fines!
   I wonder if any formulators out               that you must press so hard that it                  But back to my to my real beef:
there have ever run a tablet press,              could be used as ammo in your                     There are too many fines every-
really run a press. And I’m not talk-            shotgun. Hey, now there’s an idea.                where. Why do companies spend so
ing about a wimpy run that lasts 5               Maybe these formulators could go                  much time working powders and
minutes, either. In fact, I know that            into making artillery rounds, and                 granulating them when they end up
no formulators have ever run a                   maybe they could hire some of                     on the press as a pile of dust?
tablet press under production con-               their buddies from the granulation                   I’d like you formulator and granu-
ditions. If they had, I doubt                    department to go with them.                       lator guys to get out there and look
whether they’d be formulators.                      By the way, while I’m at it, I’ve              at the issues. The fines are every-
   Having run a press for years, I               never, ever met a supervisor who                  where, and it’s really a problem.
think the only folks more mis-                   knows anything more than how to                   Think about it: You guys cannot be
guided than formulators are people               deliver a stack of paperwork.                     making a good product when 30 to
who think they know how to gran-                 When it comes time to fix a prob-                 50 percent of it is dust. I know, the
ulate. Maybe we could put these                  lem, they become politicians:                     formulators will say that the fines
would-be formulators in a room                   “Well what do you think the prob-                 help disintegration. And I’ll reply,
with the mill operators, throw in a              lem is?” they ask. It’s never said, but           “Baloney!” The fines are killing the
few supervisors, and lock the door.              the press operators must be think-                press run, they don’t compress well,
Then I’d gather the people who                   ing: “You have got to be kidding!                 and there is no benefit to fines. You
run the tablet press and make some               Why does the handbook say I                       call yourself a formulator, but any-
real products. There won’t be any                must consult you, the boss, when                  one—you don’t need an advanced
of this superfine stuff that doesn’t             you don’t have a clue about what                  degree—can grind powders into a
disintegrate for 3 weeks, the stuff              to do?”                                           pile of dust.                   M.T.




tabletting run times                                              Table 1                                                Michael D. Tousey is
and cleaning fre-                                                                                                        owner and technical
quency. Table 1 re-       Excessive fines can
                                                                                                                         services director of DI
peats these points.
   If I were allowed
                          • Remove the oil from punches, leading to tight punches that leave black specks in the tablets Pharma Tech, 152
                          • Reduce the effectiveness of the formulation’s powdered lubricant, increasing the required
just one statement          ejection force
                                                                                                                         Wilkinson Drive,
on particle size dis-     • Decrease yields while increasing the amount of dust collected and the frequency of cleaning  Westminster, SC
tribution, it would       • Cause capping and lamination                                                                 29693. Tel. 864 657
be this: Most formu-      • Decrease content uniformity and impede product flow
lations contain too
                                                                                                                         5400, fax 864 647
many fines, and by                                                                                                       1155.         Website:
“most,” I mean about 95 percent of them. If the people                        www.dipharmatech.com. Tousey has been involved in the
responsible for formulation understood compression,                           pharmaceutical industry since 1973, including work at
they would never make a product’s particle smaller than                       Thomas Engineering, Shaklee, Pennwalt Stokes-Merrill,
what’s necessary to achieve the target dissolution rate. If
more products had better particle size distribution (fewer                    and Lakso. He founded his company in 1989. Tousey is a
fines), the press would run better and longer with less                       member of the Editorial Advisory Board of Tablets &
cleaning and fewer defects.                                     T&C           Capsules.