Optimal Tablet Press Operation
`Machine versus Granulation
`
`Mldnael D.Tousey
`
`Properly defining and
`understanding basic tablet
`press operations and
`functions can help solve
`common tablet
`
`" compression problems.
`‘ Successful tablet runs
`come from quality
`machine performance.
`granulation performance,
`and operator performance.
`
`Micllm,-I C T»:-use-y
`is the teclnicd service
`rirector and owner of
`Dorado International. Inc., a
`I
`.
`I
`.
`and training company, 152
`Wikerson Drive, Westninstet.
`SC 29693, tel. %4.647.5400.
`salesfldoradointernationalcom.
`
`52 h-rdultlg .uwmRv2oo2
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`Page 1 of 5
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`tablet press is one of the most complex machines used
`in the manufacturing enviromnent. Clearly defining the
`basic principles in tablet press operation is essential to
`having a successful nut. Learning key factors can help
`to avoid the many obstacles that can interrupt a successful run.
`Worldwide, more than I8 different companies make tablet
`presses. All tablet presses operate in the same basic way with only
`a few exceptions. This fact allowed the industry to define and
`create a standard for tablet press machines and tablet press tool-
`ing, which was published in the Tablet Specification Manual
`( TSM) by the American Pharmaceutical Asociation. The TSM
`can be acquired through any tooling or tablet pres supplier. This
`article discusses how tablet press perfomiance can be optimized
`by clearly distinguishing between granulation and machine
`issues; focusing on the importance of flow, compression, and
`ejection; and perfomiing the necessary maintenance and qual-
`ity control checks.
`
`Tablet press and ganulation
`Clearly defining the role of the operator is important in any
`endeavor, but it is especially critical in the successful manu-
`facture of a good tablet. An experienced tablet press operator
`can take a marginal granulation and make it work successfully
`and can differentiate between a machine-related issue and a
`
`granulation-related issue.
`Many granulation problems can be solved on the press, but
`they can be created on the press as well. A successful rim can be
`defined as an operation of the tablet press for a predetennined
`length of time without continued tablet problems such as pick-
`ing, capping. weight variations, and hardness variation. In
`addition, the tablet press and tooling must complete the run
`without being damaged. A successful tablet press run can be
`defined as one that produces excellent tablets with minimum
`downtime and little to no wear to the mechanical components
`of the press and press tooling. Supervisors may wonder, is this
`possible? Yes, it is very possible.
`The first step in obtaining a successful run is performing
`proper cleaning and setup. If cleaning and setup are conducted
`completely and correctly, two-thirds of that successful run is
`accomplished. However, one must remember to differentiate
`between the granulation and the machine.
`
`Machine function
`Again, the purpose is to be fundamental. Taking into account
`the tablet press in sections of function, the three main issues of
`wvm ml ‘Wm:-.‘-'.l: ‘um
`
`Grunenthal GmbH Exhibit 2040
`
`Rosellini v. Grunenthal GmbH
`
`IPR20l6-00471
`
`

`
`
`
`Figure 1: A depiction of a simple four-station rotary tablet press
`showing the basic key functions in the direction of rotation: (right to
`left) die fill, weight adjustment, compression, and ejection. (Figure
`provided by Thomas Engineering Inc.)
`
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`Figure 2: A tablet press does not weigh the granulation; weiyit is
`equal to the volume of till within the die cavity. (Figure provided by
`Thomas Engineering Inc)
`
`the product—granulation process are flow, compression, and
`ejection. Flow is the ability of the granulation to flow like granu-
`lated sugar as opposed to flour, for example. Compression is the
`formation of a tablet within the die, and, simply put, ejection is
`getting the finished tablet out of the die (see Figure l).
`Solving a problem on the machine must start with the fol-
`lowing thought process: flow, compress, and eject. The ques-
`tion then becomes whether the product issue is related to flow,
`compression, or ejection. The main sections of the press related
`to function are the press feed system, the compression station(s),
`and the ability to eject the tablet from the die and get the tablet
`safely off the tablet press.
`The order of action is important to understand when defin-
`ing problems. For example, the weight must be stable to com-
`press a tablet to a consistent final tablet hardness. Optimizing
`granulation flow and consistency must begin by evaluating
`machine speed. The average press speed of 3000 tablets/min
`means that one is manufacturing 50 tablets/s. Granulations
`that are developed on a laboratory tablet press otten will not
`work on a higher—speed machine without some change in the
`granulation’s ability to flow, compress, and eject. Some tablet
`presses have features that will help with these problems but
`will not always solve them.
`
`54 Ptauerlidl.-clrdqy .IANuARv2oo2
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`Page 2 of5
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`Flow
`
`The press feed system. The main components of the press feed
`systems are the product hopper, the feeder, the till cam, the
`weight cam, the scrapper blade assembly, and the recirculation
`channel. On a tablet press, a volume of granulation filled con-
`sistently into the die cavity determines tablet weight (see Fig-
`ure 2). A tablet press does not preweigh the granulation. The
`weight is obtained by overfilling the die cavity and then push-
`ing excess granulation out of the die and guiding it into a chan-
`nel, thereby ensuring that the excess cannot spill back into the
`die cavity.
`The paddle feeder. The hopper and feeder are designed to de-
`liver product from a static position and get it moving with the
`rotational speed of the machine. The feeder does not push
`granulation into the die; it delivers granulation over the die cav-
`ity so that it can flow into the die cavity. The paddle speed can
`be adjusted to allow the granulation to accelerate until it matches
`the rotational speed of the turret.
`Selecting the proper till (am. The fill cam determines how
`much the die will overfill. Overfill is needed to get good, con-
`sistent tablet weight. Consistent flow of granulation into the
`die will provide the needed reproducibility and consistency,
`tablet to tablet. Too much overfill means that a high percent-
`age of powder in the die gets pushed out of the die and must
`travel back into the feeder. The granulation travels repeatedly
`into and out of the feeder and the die, a process called over-
`working the granulation. The more often the granulation re-
`circulates and travels through the feeder, the more likely the
`granulation will break down and cause increased weight fluc-
`tuation, particle—size reduction, density changes, and dust. To
`prevent this problem, select the proper fill cam to get a mini-
`mum overfill of no more than 20% by volume within the die
`cavity (see Figure 3).
`Fines control. Dust on a press usually is defined asfines. Fines
`are fine particles of granulation that easily become airborne. The
`higher the percentage of fines, the more likely that common
`tablet defects such as weight variations, hardness variations, cap-
`ping, picking, sticking, and content uniformity issues will occur.
`Fines can absorb the lubricating properties of oils and greases
`used to keep mechanical components moving freely on the press.
`The higher the percentage of fines, the more need to focus on
`dust collection, component lubrication, and final yields.
`Weight control. The weight cam and scrapper assembly are the
`heart and soul of making a good tablet Moving the adjustable
`weight cam during operation on a continual basis controls the
`final tablet weight. Moving the cam upward pushes excess granu-
`lation out of the die, resulting in a reduced final tablet weight.
`Increasing the fill into the die means moving the weight cam
`down to reduce the amount of granulation being pushed back
`up and out of the die. The scrapper assembly scrapes the excess
`granulation away from the die opening and directs it into the
`recirculation channel. The scrapper blade must be spring-loaded
`to follow the surface of the die table. The scrapper blade must
`have a straight and semisharp surface to ensure that the die sur-
`face is scraped cleanly. Particle-size variations are proportion-
`ate to proper die fill. A large particle scraped from the die will
`result in greater weight fluctuations.
`
`

`
`Figure 3: Selecting ttie proper till cam provides the correct overtill
`within the die cavity. Proper overfill is essential to achieving good
`weight control. (Figure provided by ‘lhomas Engineering Inc)
`
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`Figure 4: Precompression removes air from the granulation and
`extends the dwell time. (Figure provided try Thomas Engineering Inc)
`
`Granulation flow pattern. Recirculation of the granulation is
`part of the operation. When excess granulation is pushed out
`of the die cavity, that granulation must be fed back into the
`feeder. Controlling the amount of granulation that is recircu-
`lated is very important. Too much granulation in the recircu-
`lation channel may cause the granulation to compact and den-
`sify if the granulation is sensitive to compaction. Granulations
`that are friable can break up, thereby increasing the amount of
`fines. (A small percentage of fines is acceptable; they actually
`enhance the tablet appearance. Granulations that have a nar-
`row particle-size profile tend to look granular. Granulations
`with a wider particle-size profile, including a small percentage
`of fines, have a much more compacted and shiny appearance,
`which is more desirable to consumers.)
`Particle-size profiles. Generally speaking, the granulation
`particle-size profile increases as the size of the tablet increases.
`A very small tablet such as an oral contraceptive tends to have
`a very fine particle profile — from 240 to 100 mesh. A larger
`capsule—shaped tablet, such as a common 0.330 X 0.850 in.
`tablet, will have a larger particle—size target with a profile more
`in the 180-60 mesh range. The bigger the tablet, the better it
`is to have a larger particle-size profile. The particle-size pro-
`file must fall in line with the final tablet size.
`
`56
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`h3Ifli.'8IitIlTuIIlIfl.IANuARY2ooz
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`Page 3 of 5
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`Compression
`The main components of compression consist of the precom-
`pression rolls, the main compression rolls, and the punch head
`configuration.
`Compression cycle. Compression of the granulation is accom-
`plished by pressing the punches together between pressure rolls.
`Most presses now have two compression stations: precompres-
`sion and final compression.
`Precompression can be used in two ways. The main purpose
`is to remove the air trapped within the granulation. Precom—
`pression also helps eliminate the air that is pushed into the
`granulation by the upper punch tip — the deeper the cup depth
`of the upper punch tip, the more air that gets pushed into the
`granulation. The other main purpose for precompression is to
`increase dwell time, which results in more consistent tablet-to-
`tablet hardness (see Figure 4). Again, most granulations must
`be pressed lightly or air will become trapped. Trapped air con-
`gregates along the top of the tablet band where the cup of the
`upper punch meets the band. This is called capping.
`Capping. First, it is important to understand that the diaine—
`ter of the upper punch tip is slightly smaller than the diameter
`of the lower punch tip. The lower punch tip stays in the die at
`all times — down for fill and up for weight control and through
`ejection. The lower punch tip stays in the die tightly to keep
`granulation from leaking between the tip and the die wall (see
`Figure 5).
`The upper punch tip is smaller because this is where the air
`leaves the die during compression. lfthe upper punch tips were
`the same size as the lower punch tips, then the air would be en-
`trapped. The tablet caps on the top of the tablet because that is
`where the air is pushed out. When the air is pushed out, it is
`also pushing the lighter, finer particles with it. Hence, if the
`tablet is not given time to compress fully, capping occurs. Also,
`these fines are pushed to the same location, and they have a ten-
`dency to not adhere to one another (see Figure 6).
`Punch-head configuration. The punches are pressed together
`between pressure rolls to form the tablet. The length of time the
`punches are under pressure is called dwell time. There are three
`commonly used head profiles: US standard TSM, domed head
`TSM, and European head. The head flat on the domed head and
`the European head profiles is slightly larger than that of the US
`standard profile. This larger diameter provides for greater dwell
`time during compression. Many dwell—sensitive granulations
`will have increased hardness with longer dwell times. To deter-
`mine whether a product is dwell sensitive, establish good weights
`and hardnesses, then increase press speed while maintaining
`good weight control. If tablet hardness drops off quickly with
`increased speed, then the product is dwell sensitive.
`The other advantages of the domed head and the European
`head profiles allow for a smoother transition and less-abrupt
`transfer onto the pressure rolls because the head profile has a
`larger radius than that of the standard TSM angular head
`design. This smoother transition relates to improved tool life
`because wear is reduced with the domed design. The other crit-
`ical issue to be aware of is that the European head profile is a
`narrower head profile with a 30° inside-head angle as opposed
`to the standard and domed inside-head angle of 37°. The sig-
`
`

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`
`
`Figure 5: The top of this tablet is coming off the rest of the tablet This
`is called capping.
`
`Figure 6: Air release on the press is controlled by the punch tip design
`and the point of compression within the die — the deeper the upper
`punch entry. the farther the air must travel to be released. (Figure
`provided by Thomas Engineering, Inc.)
`
`nificant difference is that a machine configured with European
`cams must be used with a European head profile. They are not
`interchangeable with machines that use US and domed head
`profiles and matching cams. Machines used in North America
`typically are supplied with US cams.
`A basic compression example. An example of a basic compres-
`sion process is the making of a snowball. Kids (in cold climates
`— sorry to my friends in Puerto Rico) know that when
`snowflakes are large and wet, they can pick up a handful of snow,
`compact it quickly, and throw it at their buddy successfully. On
`days when the snow is very fine and light (low bulk density)
`and dry (low moisture content), if I compact it in the same way
`as the wet snow and throw it at my buddies, the snowball will
`never reach its intended target. When the snow is fight and dry
`and fine it must be compressed for a longer period of time (dwell
`time).
`Light, fine, and dry particles also are more sensitive to over-
`compression. Overcompressed particles laminate because they
`no longer lock together. The key is to understand the nature of
`a granulation. Operators who are lucky enough to produce one
`and only one product day after day know that the granulation
`does have variations like snow has. Some granulations can have
`
`58 HIIt8Il'tlITe¢I0hflJANuARY2oo2
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`Page 4 of 5
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`overly wet areas and dry areas in the same batch. Recognizing
`this is important; otherwise, one may conclude that there is a
`machine problem. View the machine as a tool to make the granu-
`lation perform. Monitoring press speed and controlling dwell
`times are essential functions of operating the press to match
`the granulation. (By the way, be sure to feed this information
`to your buddies in granulation — they think you still don‘t
`know how to operate the press.)
`
`Ejection
`The main function of ejection is to get the tablet out of the die.
`The ejection cam, lower punch length, lower punch tip condi-
`tion, take-off blade, machine speed, and proper mix of lubri-
`cant into the granulation all contribute to proper tablet ejection.
`Ejection height should be set so that the lower punch tip is
`even with or slightly above the die. This ensures that the tablet
`is pushed completely out of the die. If the lower punches are
`worn and have different lengths, then the ejection height will
`not be consistent. Because punches tend to wear down, he sure
`the punch tip is kept smooth. A dented or rough punch tip often
`indicates poor handling. The punch cup also must be polished
`to keep the granules from sticking to the surface of the punch
`to eliminate the tendency of the granulation to pull away from
`the surface of the tablet. This is commonly referred to as stick-
`ing and picking. Sticking and picking also can be a result of gran-
`ules that are not dry inside. When compressed, case-hardened
`granules will not be protected by the dry lubricant that is mixed
`in to help prevent sticking and picking. A wet granule will stick
`to the punch surfaces.
`Once the tablet is pushed out of the die, it is guided ofi the
`machine by the take-off blade. The take-off blade guides the
`tablet off the surface of the lower punch and die table and
`directs it down the tablet ejection chute. The blade must be
`clean and level. If the take—ofi° blade is set too high, the tablet
`might chip or even break, and densified tablet pieces will get
`into the flow of granulation causing weight, hardness, and most
`likely dissolution issues.
`
`A good tablet
`The main issues in making a tablet are tablet weight, hardness,
`thickness, friability, content uniformity, and appearance.
`Weiglt control. Weight control was discussed previously. Tablet
`weight is determined by a volume of granulation filled consis-
`tently into the die cavity. A tablet press does not preweigh the
`granulation. The weight is a result of overfilling the die cavity,
`then pushing excess granulation out of the die and guiding the
`excess granulation into a channel, making certain that it can-
`not spill back into the die cavity. Good weight control is the
`essence of making a good tablet. Always check weights first. then
`thickness and hardness.
`
`Tablet-hardness control. The main factors are weight, thick-
`ness, punch length, press speed, upper-punch penetration, and
`die condition. Don‘t try to solve hardness issues without hav-
`ing consistent weights first.
`thickness and punch length. Ptmches should be checked in—house
`regularly after each cleaning to ensure that they are maintained.
`New punches are made to be :0.00l in. Worn dimensions
`
`

`
`depend completely on the end product. Some companies allow
`for a length variation of ⫾0.004 in., which is extreme.
`Dwell time. As discussed previously, dwell time is time under
`pressure, which relates to punch-head flat and press speed.
`Punch penetration. Upper-punch penetration is how far the upper
`punch enters the die. Old presses have a nonadjustable upper-
`punch penetration set at 6 mm. New and more modern ma-
`chines have adjustable punch penetration. If the upper punch
`enters the die at 6 mm, then the air has a long way to travel to
`escape. Making the tablet higher in the die allows the air to evac-
`uate sooner and allows for more consistent hardness control
`and higher press speed.
`Die condition. Die condition can influence tablet hardness and
`appearance. As a tablet is compressed, radial forces will create
`compression rings within the die. Over time, these wear rings
`will become exaggerated. Compressing a tablet in a worn die
`can give the appearance that the tablet is capping. Hardness
`cannot be controlled, and the tablet band (sides) will not be
`hard, smooth, and shiny.
`
`The role of supervisors and operators
`Supervisors and operators should do the following:
`● When the press is apart with no tooling, visually inspect all
`of the working areas of the machine (a flashlight is very help-
`ful). Good or normal metal wear means that the metal is pol-
`ished and shiny. Bad metal wear means that the metal has be-
`come dull, abraded, rough, and discolored.
`● Visually inspect the punches and dies. Become familiar with
`the wear patterns and determine what is causing them. Look
`into the punch sockets and use a flashlight and a mirror if
`needed for the lower punches. As granulations cake in the
`socket they become shiny and look like steel. Buildup in the
`socket will cause the punches to run tight, resulting in short-
`ened punch life. Inspect punch sockets closely.
`● Never dry run a machine. Some machine manufacturers may
`claim that the machines have various safeties and that con-
`ducting a dry run is OK. It’s not OK. Make sure that there is
`powder between the dies.
`● Rotate the machines slowly and listen for metal-to-metal
`scraping sounds. The sounds will eventually go away but not
`before causing some damage. Don’t run the machine until
`you solve this problem. One trick is to rotate the machine after
`each subassembly is complete (i.e., after installing the upper
`punches, the feeder, and the dust nozzles).
`● Check weights often and routinely.
`● Listen to the machine. Changes in the moisture content of the
`granulation will make the machine sound differently. A tough
`and abrasive granulation makes the press sound harder and
`rougher compared with the sounds produced when using a
`softer granulation.
`Inspect the tablets. Look for gray and black specks. These dis-
`colorations come from granulation packing in the feeder or
`on the die table, from a lack of lubrication in the upper punch
`sockets, misaligned punches and dies, and metal-to-metal
`contact.
`
`Summary
`Good operators are professionals. They can differentiate between
`the machine and granulation. They know how to adjust the
`machine within existing parameters to get the maximum
`performance from the machine and the granulation. Good
`operators know that the presence of fine airborne particles means
`that more frequent cleaning and higher frequency of punch
`lubrication are required. Granulations vary within each batch
`and from batch to batch. The operator must recognize this and
`adjust the machine accordingly. Don’t leave the problem for the
`next shift. Proper monitoring and frequent checking will pro-
`vide more-continuous operation. Sometimes a machine can run
`for days and other times, only for a few hours — it all depends
`on the initial cleaning, proper setup, and keeping the dust and
`fines to a minimum.
`In the tablet press room, you know you’re in trouble if you
`hear
`● “The mechanics do that.”
`● “It’s set at the factory.”
`● “We’re not allowed to touch that.”
`● “We don’t need to know what that does.”
`● “We don’t use that feature.”
`● “Tablet presses are meant to run dirty.”
`Operators should know their tablet press because they are
`the experts. Under the umbrella of the SOP/batch record, they
`use all available press machinery options to optimize each batch.
`Mechanics assist operators with higher level problems. Machine
`setup, fundamental operation, tool–die installation, cam changes,
`and press cleanup are operator functions. Supervisors address
`productivity improvement and employee motivation. They drive
`positive change with a questioning attitude.
`Constant feedback from the coating and packaging depart-
`ment should be viewed as a positive improvement strategy. The
`challenge of implementing positive changes in the tablet press
`room is important. It is one thing to learn the basics; it is quite
`another to effect positive change. Constant daily reinforcement
`of basic tablet manufacturing principles is absolutely required
`for ultimate success. Recognize that to effect true change,
`obtaining a broader agreement with support departments may
`require both education and diligence. We must understand, rec-
`ognize, and track machine performance, granulation perform-
`ance, and operator performance. All three are interrelated. PT
`
`FYI
`On-line toxicological database
`Chemical Abstracts Service (CAS),a division of the American Chemical
`Society,has introduced its on-line toxicological database,Toxcenter, which is
`available now through the Scientific & Technical Information Network at
`www.fiz-karlsruhe.de/stn.html.
`The database,updated weekly,includes more than 5 million records derived
`from pharmacological,biomedical,and chemical literature.The database also
`contains bibliographic information about methodology,industrial hygiene,
`legal issues and standards,and the toxicological,pharmacological,biomedical,
`and biochemical effects of drugs,chemicals,and food.
`For more information,contact CAS,PO Box 3012,Columbus,OH 43210-0012,
`tel.614.447.3600,fax 614.447.3713,www.cas.org.
`
`60 Pharmaceutical Technology JANUARY 2002
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`www.pharmtech.com
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