Tablet Press Instrumentation

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Tablet Press Instrumentation Michael Levin Metropolitan Computing Corporation, East Hanover, New Jersey, U.S.A. INTRODUCTION This article is designed to facilitate the understanding of the general principles of tablet press instrumentation and the benefits thereof by the formulators, process engineers, validation specialists, and quality assurance personnel, as well as production floor supervisors who would like to understand the basic standards and techniques of getting information about their tableting process. HISTORY OF TABLET PRESS INSTRUMENTATION In 1952 – 1954 Higuchi and his group [1] have instrumented upper and lower compression, ejection, and punch displacement on an eccentric tablet press, and pioneered the modern study of compaction process. This work was followed by Nelson [2,3] who was the member of the original group. In 1966, a U.S. patent was granted to Knoechel and co- workers [4] for force measurement on a tablet press. This patent was followed by two seminal articles in Journal of Pharmaceutical Sciences on the practical applications of instrumented rotary tablet machines. [5,6] A number of other patents related to press instrumentation and control followed from 1973 on ward. [7 – 15] Despite the availability of published designs for instrumenting rotary presses, much of the early work on compaction properties of materials was done on instru- mented single punch eccentric presses primarily, due to the relative ease of sensor installation, as well as availability of punch displacement measurement. [16 – 18] In mid-1980s, custom-made press monitoring systems were described, [19,20] and the first commercial instrumen- tation packages became available, including both the systems for product development and press control. The first personal computer-based tablet press monitor was sold in 1987, and the first Microsoft Windows-based press instrumentation package in 1995. A new era of compaction research has begun with the introduction of an instrumented compaction simulator [21] in 1976, while a compaction simulator patent was issued as recently as 1996. [22] A new generation of “compaction simulators” was born when a mechanical press replicator was patented in the year 2000. [23] A good expose ´ of the early stages of press instrumentation and resulting research is presented in review articles by Schwartz, [24] Marshall, [25] and Jones. [26] A comprehensive review can be found in a relatively recent paper by C ¸ elik and Ruegger. [27] For other historical information on the press instru- mentation, the reader is encouraged to peruse Ridgeway Watt’s [28] volume. There have been a number of papers published on various disparate instrumentation topics, and in a recent volume by Mun ˜os-Ruiz and Vromans, [29] there are two good articles on the subject—but, unfortunately, they deal with marginal issues of single station press and instrumented punch only. DATA ACQUISITION PRINCIPLES: FROM TRANSDUCERS TO COMPUTERS To monitor and control a tablet press, certain sensors must be installed at specific locations on the machine. These sensors are called transducers. In general, a transducer is a device that converts energy from one form to another (e.g., force to voltage). Tablet press transducers typically measure applied force, turret speed, or punch position. Because the signals coming from such transducers are normally in millivolts, they need to be amplified and then converted to digital form in order to be processed by a data acquisition system. Piezoelectric Gages Historically, high impedance piezoelectric transducers that employ quartz crystals were used in early stages of press instrumentation. When subject to stress, the crystal accumulates electrostatic charge that is directly propor- tional to the applied force. Both low and (more modern) high impedance piezoelectric gages have high-frequency response, but may exhibit signal drifting due to charge Encyclopedia of Pharmaceutical Technology DOI: 10.1081/E-EPT 120012030 Copyright q 2002 by Marcel Dekker, Inc. All rights reserved. 1 ©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc. MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

description

Review of measurements that allow you to monitor and optimize the tableting process

Transcript of Tablet Press Instrumentation

Page 1: Tablet Press Instrumentation

Tablet Press Instrumentation

Michael Levin

Metropolitan Computing Corporation, East Hanover, New Jersey, U.S.A.

INTRODUCTION

This article is designed to facilitate the understanding of

the general principles of tablet press instrumentation and

the benefits thereof by the formulators, process engineers,

validation specialists, and quality assurance personnel, as

well as production floor supervisors who would like to

understand the basic standards and techniques of getting

information about their tableting process.

HISTORY OF TABLET PRESSINSTRUMENTATION

In 1952–1954 Higuchi and his group[1] have instrumented

upper and lower compression, ejection, and punch

displacement on an eccentric tablet press, and pioneered

the modern study of compaction process. This work was

followed by Nelson[2,3] who was the member of the

original group.

In 1966, a U.S. patent was granted to Knoechel and co-

workers[4] for force measurement on a tablet press. This

patent was followed by two seminal articles in Journal

of Pharmaceutical Sciences on the practical applications

of instrumented rotary tablet machines.[5,6] A number of

other patents related to press instrumentation and control

followed from 1973 on ward.[7 – 15]

Despite the availability of published designs for

instrumenting rotary presses, much of the early work on

compaction properties of materials was done on instru-

mented single punch eccentric presses primarily, due to

the relative ease of sensor installation, as well as

availability of punch displacement measurement.[16 – 18]

In mid-1980s, custom-made press monitoring systems

were described,[19,20] and the first commercial instrumen-

tation packages became available, including both the

systems for product development and press control. The

first personal computer-based tablet press monitor was

sold in 1987, and the first Microsoft Windows-based press

instrumentation package in 1995.

A new era of compaction research has begun with the

introduction of an instrumented compaction simulator[21]

in 1976, while a compaction simulator patent was issued

as recently as 1996.[22]

A new generation of “compaction simulators” was born

when a mechanical press replicator was patented in the

year 2000.[23]

A good expose of the early stages of press

instrumentation and resulting research is presented in

review articles by Schwartz,[24] Marshall,[25] and Jones.[26]

A comprehensive review can be found in a relatively

recent paper by Celik and Ruegger.[27]

For other historical information on the press instru-

mentation, the reader is encouraged to peruse Ridgeway

Watt’s[28] volume. There have been a number of papers

published on various disparate instrumentation topics, and

in a recent volume by Munos-Ruiz and Vromans,[29] there

are two good articles on the subject—but, unfortunately,

they deal with marginal issues of single station press and

instrumented punch only.

DATA ACQUISITION PRINCIPLES:FROM TRANSDUCERS TO COMPUTERS

To monitor and control a tablet press, certain sensors must

be installed at specific locations on the machine. These

sensors are called transducers. In general, a transducer is

a device that converts energy from one form to another

(e.g., force to voltage). Tablet press transducers typically

measure applied force, turret speed, or punch position.

Because the signals coming from such transducers are

normally in millivolts, they need to be amplified and then

converted to digital form in order to be processed by a data

acquisition system.

Piezoelectric Gages

Historically, high impedance piezoelectric transducers

that employ quartz crystals were used in early stages of

press instrumentation. When subject to stress, the crystal

accumulates electrostatic charge that is directly propor-

tional to the applied force. Both low and (more modern)

high impedance piezoelectric gages have high-frequency

response, but may exhibit signal drifting due to charge

Encyclopedia of Pharmaceutical Technology

DOI: 10.1081/E-EPT 120012030

Copyright q 2002 by Marcel Dekker, Inc. All rights reserved.

1

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Page 2: Tablet Press Instrumentation

leakage (approximately 0.04% decay per second can be

seen in modern piezoelectric transducers). Nowadays,

the preferred way of instrumenting tablet presses is with

strain gages.

Strain Gages

Strain gages are foil, wire, or semiconductor devices that

convert pressure or force into electrical voltage. When a

stress is applied to a thin wire, it becomes longer and

thinner. Both factors contribute to increased electrical

resistance. If an electrical current is sent through this wire,

it will be affected by the changes in the resistance of the

conduit. This principle is used in strain gage-based

transducers. Foil gages, known for robust application

range, useful nominal resistance, and reliable sensitivity

control, are most commonly used for instrumentation of

compression, precompression, and ejection forces. Semi-

conductor-based strain gages are inherently more sensitive

but suffer from high electrical noise and temperature

sensitivity. Such gages are not commonly used in tablet

press instrumentation except for measurement of die-wall

pressure and take-off forces.

Wheatstone Bridge

Wheatstone bridge (Fig. 1) is a special arrangement of

strain gages that is used to ensure signal balancing. The

“full” bridge is composed of two pairs of resistors in a

circle, with two parallel branches used for input and two

for signal output. By applying the so-called excitation

voltage (typically, 10 V DC) to the bridge input and

changing the resistance of different “legs” of the bridge by

adding special resistors, we can make sure that there is a

zero output voltage when no load is applied to the

transducer. This is called zero balance. Once the bridge is

balanced, a small perturbation in the resistance of any

“leg” of the bridge results in a nonzero signal output.

The output of the Wheatstone bridge is normally

expressed in millivolts per volt of excitation per unit of

applied force. For example, sensitivity of 0.2 mV/V/kN

means that applying, say, 10 kN force and 10 V excitation

will produce 20 mV output. To utilize such output, it

usually needs to be amplified several hundred times to

reach units of volts.

Another important function of the bridge is balancing

of temperature effects. Although individual strain gages

are sensitive to temperature fluctuations, Wheatstone

bridge arrangement provides for temperature sensitivity

compensation, so that the resulting transducer is no

longer changing its output to any significant degree when

it heats up.

Because the output of these bridges is in the range of

millivolts, the cables utilized to carry the signal are

normally shielded with a braided or foil-lined sheath

around individual wires. The shield, as a rule, is connected

to the amplifier, but never touches the actual instrumented

equipment (i.e., tablet press). If this rule is violated, a

ground loop may generate electrical noise and present a

dangerous electrical shock hazard.

Gage Factor

The gage factor is a specific characteristic of a strain gage.

It is calculated as the change in resistance relative to unit

strain that has caused this change. Strain gages that are

commonly used for tablet press instrumentation are made

from copper–nickel alloy and have a gage factor of about

2. In a typical bending beam application (such as

compression roll transducer), one side of the beam

experiences tension while the other side undergoes

compression. By mounting two gages on each side, the

sensitivity of the transducer can be doubled.

Strain gages have to be bonded to areas of machine

parts that are most sensitive to applied force. Such areas

can be identified with the use of polarized light technique

that “points out” the stress distribution.

Manufacturing a Force Transducer

Usually, instrumentation designs are proprietary and

specific detail drawings are held in fiducial capacity.

Each force transducer is custom designed for a particular

machine part. Overall specifications are taken from the

actual party and/or manufacturer approved drawings.

Duplicate steel members, such as pins and cams, are

normally made from A2 tool steel in a fully annealedFig. 1 A typical Wheatstone bridge arrangement of strain

gages.

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(softened) state. Original machine parts are first annealed,

if required. The member is then machined, hardened to

Rockwell 60–64, tested, and finally, ground to specified

dimensions.

It is highly advantageous to determine stress dis-

tribution using polarized light beams identifying the areas

of maximum strain yet avoiding areas of uneven strain.

A typical procedure of transducer manufacturing in a

professional gaging lab might be as follows. Foil type

strain gages are bonded to the steel member utilizing a

high-performance 100% solid epoxy system adhesive

under controlled heating rate conditions. After intrabridge

wiring is completed using solid conductor wiring (to

prevent electrical noise), multistrand wire cabling with a

combination of foil and braided insulation is connected to

the bridge. Wire anchoring is achieved utilizing epoxy

adhesive and protected with a combination of latex-based

adhesives and/or epoxy resins. Lead wire cabling is

protected by Teflon outer shield, as well as inner braided

wire shield. The Teflon to steel joint is sealed with epoxy

but should not be subject to stresses that would cause the

cable to kink or yield in such a way as to expose the inner

braided wire shield. Protective coatings are then applied

and final postcure heating is performed for at least 2 hr at

a temperature approximately 508C above the transducer

normal operating temperature (approximately 175 or

105 8C). A silicon-based adhesive, such as RTV, is used to

fill large cavities while maintaining a low modulus of

elasticity, preventing undue influence upon the actual

strain measurement. The coating is resilient to moderate

mechanical abrasion, as well as most solvents, oils,

cleaners, etc. It is not intended for protection against

penetrating sharp objects.

A high-quality connector is then attached to the cable.

The next step is to perform offset zeroing with fixed, 1%

precision, low-temperature coefficient resistors, followed

by NIST (National Institute for Standards and Technol-

ogy) traceable calibration.

It is worth noting that, in general, the duplicate members

are not made of corrosion-resistant steel, because high

tensile strength and ability to be easily machined are

required. Prior to storage, the surface should be treated

like any high-grade tablet press punch steel will be treated;

a thin coating of oil should be used after wiping with

alcohol.

Load Cells

In some cases, where appropriate, a load cell can be used

in place of bonded strain gages.

A load cell is a strain gage bridge in an enclosure

forming a complete transducer device.

Like any properly made transducer, it produces an

output signal proportional to the applied load. Unlike

custom-made transducers that require application of strain

gages directly to press parts, load cells are self-contained

and can be placed on a press in specially machined cavities

to be easily replaced or serviced. As a drawback, load cells

generally are less sensitive or less suited to measure the

absolute force than custom-made strain gage transducers.

Load cells can be used on punch holders in a single station

press. Another example of load cell use is a die assembly

for calibration of existing traducers on a press.

Linear Variable Differential Transformer

Linear variable differential transformer (LVDT, Fig. 2) is

a device that produces voltage proportional to the position

of a core rod inside a cylinder body. It measures

displacement or a position of an object relative to some

predefined zero location. On tablet presses, LVDTs are

used to measure punch displacement and in-die thickness.

They generally have very high precision and accuracy, but

there are numerous practical concerns regarding improper

mounting or maintenance of such transducers on tablet

presses.

Proximity Switch

Proximity switch (Fig. 3) is a noncontact electromagnetic

pickup device that senses the presence of metal. On tablet

presses, it is widely used to detect the beginning of a turret

Fig. 2 Linear variable differential transformer (LVDT).

Tablet Press Instrumentation 3

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Page 4: Tablet Press Instrumentation

revolution, to identify stations and to facilitate peak

detection in tablet force control applications.

Instrumentation Amplifier and Signal

Conditioning

Signal conditioning involves primarily an amplifier that

provides the excitation voltage, as well as gain (a factor

used in converting millivolt output of the strain gage

bridge to the volt-based range of the input of the data

acquisition device).

Instrumentation amplifier is different from other

types of amplifiers in that the signal from each side of

the transducer bridge is amplified separately and then

the difference between the two amplified signals is, in

turn, amplified. As a result, noise from both sides of the

sensors is reduced.

Some instrumentation amplifiers also offer filter

functionality. A filter circuit combines resistors and

capacitors that act to block the undesirable frequencies.

It is a fact, however, that a good transducer should

provide a clean signal. Use of analog or digital filters

may cause the loss of some important portions of the

signal that one is attempting to measure. Frequency

filters may cause the measured compression force peak,

for example, to be skewed toward the trailing edge of

the peak and can yield a lower than actual peak force.

Because filters distort the signal, they must be

avoided unless absolutely necessary. In many cases,

better electronics may make filter use obsolete. For

example, the so-called antialiasing filter that is used to

condition a high-frequency signal for a slow sampling

rate is generally not required for tablet press

applications if modern fast speed data acquisition

devices are used for signal processing.

In addition to amplification, excitation, and filtering,

signal-conditioning devices may provide isolation, voltage

division, surge protection, and current-to-voltage

conversion.

Instrumentation Terms: Definitions

Several important terms may be now defined with respect

to transducers and signal conditioning:

. Full Scale (FS): The total interval over which a

transducer is intended to operate. Also, it can define

the output from transducer when the maximum load is

applied.

. Excitation: The voltage applied to the input terminals

of a strain gage bridge.

. Accuracy: The closeness with which a measurement

approaches the true value of a variable being

measured. It defines the error of reading. Good tablet

press transducers have at least 1% accuracy (with this

level of accuracy, for example, a compression force

transducer with 50 kN FS will produce at most an error

of 500 N).

. Precision: Reproducibility of a measurement, i.e., how

much successive readings of the same fixed value of a

variable differ from one another. If a person is shooting

darts, for example, the accuracy is determined by how

close to the bull’s eye the darts have landed, while the

precision will be indicated by how close the darts are

to each other.

. Resolution: The smallest change in measured value

that the instrument can detect.

. Dynamic range of a transducer: The difference

between the maximal FS level and the lowest

detectable signal. Measured in decibels (dB), it

indicates the ratio of signal maximum to minimum

levels:

dB ¼ 10 log10ðSmax=SminÞ

Some press sensors may have a rather narrow dynamic

range not necessarily correlated with accuracy. For

example, a very accurate compression roll pin designed

to measure 50 kN force may not detect 5 kN signal.

. Calibration: Comparison of transducer outputs at

standard test loads to output of a known standard at the

same load levels. A line representing the best fit to data

is called a calibration graph.

. Calibration factor: A load value in engineering units

that a transducer will indicate for each volt of output,

after amplifier gain and balance. Calibration factor is

usually expressed in relation to FS.

. Shunt calibration: A procedure of transducer testing

when a resistor with a known value is connected to one

leg of the bridge. The output should correspond to the

voltage specified in the calibration certificate. If it does

not, something is wrong and the transducer needs to be

inspected for possible damage or recalibrated.

Fig. 3 Proximity switch.

Tablet Press Instrumentation4

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Page 5: Tablet Press Instrumentation

. Sensitivity: The ratio of a change in measurement

value to a change in measured variable. For example, if

a person ate a 1 lb steak and the bathroom scale shows

2 lb increase in the body weight, then the scale can be

called as insensitive (ratio is far from unity).

. Traceability: The step-by-step transfer process by

which the transducer calibration can be related to

primary standards. During any calibration process,

transducer is compared to a known standard. National

or international institutions usually prescribe the

standards. In the United States, such governing body

is the NIST.

. Measurement errors: Any discrepancies between the

measured values and the reported results over the

entire FS. Such errors include, but are not limited to:

. Nonlinearity: The maximum deviation of the

calibration points from a regression line (best fit

to the data), expressed as a percentage of the rated

FS output and measured on increasing load only.

. Repeatability: The maximum difference between

transducer output readings for repeated applied

loads under identical loading and environmental

conditions. It indicates the ability of an instru-

ment to give identical results in successive

readings.

. Hysteresis: The maximum difference between

transducer output readings for the same applied

load. One reading is obtained by increasing the

load from zero and the other reading is obtained

by decreasing the load from the rated FS load.

Measurements should be taken as rapidly as

possible to minimize creep.

. Return to zero: The difference in two readings:

one, at no load, and the second one, after the FS

load was applied and removed.

A good transducer is one with the combined (or

maximum) error of less than 1% of the FS.

Analog-to-Digital Converters

In order to convey analog output (in volts) from a

transducer to a computer, it has to be converted into a

sequence of binary digital numbers. Modern analog-to-

digital converter (ADC) boards are sophisticated high-

speed electronic devices that are classified by the input

resolution, as well as the range of input voltages and

sampling rates.

Resolution of an ADC board is measured in bits.

Bit (abbreviation for binary unit) is a unit of information

equal to one binary decision (such as “yes or no,” “on or

off”). A 12-bit system provides a resolution of one part in

212 ¼ 4096; or approximately 0.025% of FS. Likewise, 16

bits correspond to one part in 216 ¼ 65; 536; or

approximately 0.0015% of FS (for tablet press appli-

cations, such resolution is usually excessive).

Thus, resolution of ADC board limits not only the

dynamic range but also the overall system accuracy.

Alternatively, a higher resolution may be required to retain

a certain level of accuracy within a given dynamic range.

For example, a 0.5% accurate transducer with 80 dB

dynamic range requires at least 12-bit ADC resolution.

Amplifying a low-level signal by 10 or 100 times

increases the effective resolution by more than 3 and 6 bits,

respectively. On the other hand, increasing an ADC

resolution cannot benefit the overall system accuracy if

other components, such as amplifier or transducer, have a

lower resolution.

When an input signal change is smaller than the

system’s minimum resolution, then that event will go

undetected. For example, for an FS of 10 V (corresponding

to, say, a compression transducer output of 50 kN), using a

12-bit ADC, any signal that does not exceed 2.44 mV

(12.2 N) will not be seen by the system.

The ADC boards also differ by the effective sampling

rate range. Sampling rate speed is measured in Hertz

(times per second). The signals coming from a tablet press

have a frequency of not more that 100 Hz (compression

events per second). To avoid aliasing (losing resolution of

the incoming signal due to slow sampling rate), the

sampling rate should be at least twice the highest

frequency of the signal. Most ADC boards used for data

collection in tableting applications have a sampling rate of

5–20 times larger than signal frequency. That is why

antialiasing filters are not required.

Computers and Data Acquisition Software

Overall accuracy of a data acquisition system is

determined by the worst-case error of all its components.

One should be aware of the fact that most system errors

come neither from transducers (0.5%–1% accuracy) nor

from A/D converters (0.025% accuracy) but from the

software analyzing the data (round-off errors, improper

sampling rate, or algorithms).

The speed and capacity of a data acquisition system

depend on the computer’s processor and hard drive

specifications. The real-time data from transducers is

streamlined to both the screen (for monitoring) and the

disk (for replay and analysis). Generally speaking, “real-

time” processing means reporting any change in the

phenomena under study as it happens. Interestingly, but

Tablet Press Instrumentation 5

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Page 6: Tablet Press Instrumentation

a high-speed data collection from a tablet press and a

bookkeeping home finance program used on a monthly

basis to balance the checkbook can both be related to as

“real-time” software. The difference is in the time frames.

For a tablet press, we are collecting data that need to be

sampled and processed in milliseconds (a typical

compression event may take 25 msec), while for home

bookkeeping once a month will do.

Most vendors supplying transducers, signal condition-

ing, and computer hardware adhere to practical standards,

e.g., there are some accepted norms for strain gage factors,

combined errors, sensitivity, ADC resolution, and

sampling rate. The difference between vendors is apparent

when we compare software because there are no

universally established standards of user interface. Yet

the hardware is “transparent” (i.e., invisible) to the end

user—day in and day out the user is facing the screen,

keyboard, and mouse. The ease of software use, bug-free

analysis of signals coming from transducers, reliability of

statistical computations, quality of graphs and reports, and

validatability of the system—all of the above contribute to

the quality of the data acquisition software.

Proper validation tests of a data acquisition system

should include calculation of an overall system error when

the input is known and controlled (e.g., an NIST traceable

signal generator providing a sinusoidal signal with a

known amplitude and frequency, to simulate compression

events on a press). Comparing the output (for example,

peak heights as reported by the software) to the known

input, the overall system error can be reliably established.

TABLET PRESS INSTRUMENTATION FORPRODUCT AND PROCESS DEVELOPMENT

R&D Grade Instrumentation

In a production environment, typical tablet weight control

mechanism is driven by signals that are coming from a

compression force transducer. Strain gages may be

installed on a column connecting the upper and lower

compression wheel assemblies. This transducer measures

what is generally known as “main compression,” i.e., a

diluted average of the forces acting on the upper and lower

punches. Alternatively, a load cell may be positioned in

some convenient location to register a transmitted

compression force. It is measured away from the force

application axis, and some force is lost in the transmission.

The resulting measurement may be adequate for tablet

weight control, but, even if properly calibrated, it does not

represent the absolute value of the compression force.

The R&D grade instrumentation, in contrast, requires

placing the strain gages as close to the punch tips as

possible in a vertical alignment with the direction of force

application.[30] In practice, it means placing the gages in a

compression roll pin, so that the resulting measurement

would reflect the absolute force. Thus, we can differentiate

between the force on the upper and lower punch, and

moreover, we can compare readings of the compression

force from different tablet presses.

Compression Force Measurement

On a typical R&D grade compression transducer, a

compression roll pin is machined with incisions made for

placing strain gages (Fig. 4). The actual form of these

cavities constitutes the very art of the transducer design

that is usually proprietary and is based on the know-how of

instrumentation vendor.

It hast to be noted that there could be an upper or lower

instrumented compression roll pin.

The resulting measurement of a compression force is

highly correlated with a variety of tablet properties. As

compression increases, so does tablet hardness and weight

(at constant thickness and true density), along with a force

required to eject a tablet. Many variables affect the force

of compression: press settings, press speed, punch length

variation, punch wear, and damage, formulation and

excipient properties.

Precompression Force Measurement

Similar to instrumented compression pin, there is a way

to instrument an upper or lower instrumented precom-

pression roll pin. Precompression, if it exists on a press,

is used for de-aerating and initial tamping of the powder

mass in the die and usually helps to achieve the desired

hardness without capping or lamination.[30,31] The force

Fig. 4 Compression force transducer.

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of precompression is normally a fraction of the

compression force.

Ejection Force Measurement

There are many ways to instrument an ejection cam.

A preferred arrangement of strain gages (the so-called

“shear force” design) does not require any discontinuities

in the cam surface, and, most importantly, it provides for a

very good linearity of the resulting signal (Fig. 5).

Larger ejection forces may lead to an increased wear on

tooling and eject cam surface. Ejection force may also be

used to evaluate the effectiveness of lubrication (of both

the press and the product) and punch sticking. Sensitivity

and linearity of an ejection transducer are design

dependent: shear force designs are always preferable

over split cam or cantilevered beam designs.

Take-Off Force Measurement

Take-off force is monitored by mounting a strain gage to a

cantilever beam on a press feed frame (in front of the take-

off blade, Fig. 6). It is done to measure adhesion of tablets

to lower punch face. Such adhesion is indicative of

underlubricated granulation, poor tooling face design, die-

wall binding, and tablet capping.[32,33]

Speed Measurement and Station IDDetermination

Station identification and press speed are usually obtained

by means of a revolution counter (proximity switch). It is

installed on the press in order to mark the beginning of

a turret revolution and thus enable station identification

and speed calculations by system software.

In addition, a linear arrangement of proximity switches

can mark the beginning and end of a compression event

(information that is vital for tablet weight controllers) and

also indicate missing punches.

Other points of instrumentation on a tablet press are as

follows:

. A rotary press pull-up cam can be instrumented to

measure the upper punch pull-up force (the force

required to pull up the upper punch from the die).

Likewise, the lower punch pull-down force is

measured on a bolt holding the pull-down cam.[34] It

is useful in determining the smoothness of press

operation (extent of lubrication, cleanliness of the

machine, and long batch fatigue buildup).

. Punch displacement measurements are easily done on

a single station press by attaching LVDT to the punch.

On a rotary press, such measurements can be done by

means of slip ring, telemetry, or instrumented punch.

Punch displacement profiles may be used in conj-

unction with compression force to estimate work of

compression and work of expansion (measure of

elasticity). Because capping tendency increases with

the punch penetration depth, it may be desirable to

monitor actual punch movement into the die. The

shape of a force–displacement curve is an indication

of the relative elasticity or plasticity of the material;

whereas plastic deformation is desirable for stronger

tablets, excess plasticity usually results in tablets that

tend to cap and laminate.[35 – 37]

. Radial and axial die-wall force measurements also

provide an insight into the compaction mechanism of

the material and may indicate a die-wall binding

(sticking) that is, in effect, a negative pull on lower

punch. The radial die-wall pressure due to friction is

material-specific and is more evenly distributed inside

the die with an addition of a lubricant.[38 – 44]

Instrumentation of the die presents a technological

challenge because pressure is distributed nonlinearlyFig. 5 Instrumented ejection cam.

Fig. 6 Instrumented take-off bar.

Tablet Press Instrumentation 7

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Page 8: Tablet Press Instrumentation

with respect to tablet position inside the die and

depends on tablet thickness.[45,46]

. In-die temperature can be monitored for heat-sensitive

formulation, such as ibuprofen.[47,48]

Instrumented Punch

Several vendors offer instrumented punch, i.e., a punch

that has strain gages and other instrumentation built-in.

The data are then accumulated or transmitted via telemetry

to a stationary computer. Such devices are versatile

enough to report compression forces and either punch

displacement or acceleration, and, at least in theory, they

can be easily moved from press to press.[49,50] However,

one should keep in mind that each instrumented punch is

limited to one size and shape of the tooling, and is limited

to one station, compared to roll pin instrumentation that

reports data for all stations and any tooling. In addition,

instrumented punches are either rather cumbersome to

install, or else they report a useless measurement of punch

acceleration instead of punch displacement. Attempts to

calculate displacement from acceleration so far could not

be validated.

Single Punch Press for R&D

Single punch eccentric presses are often used in early

stages of formulation development because they do not

require a large amount of powder. Another benefit is that

they allow relatively inexpensive measurements of die

forces and punch displacement (there is no rotation of die

table and therefore no need to use expensive telemetry

methods). This is the primary reason why so much basic

research and product development were done on eccentric

machines.[51] Negative considerations are that a special

tooling is required (usually, F tooling), and also that speed

of compaction is too slow compared to rotary presses. As it

will be seen later, the speed is a crucial factor in tableting

process and therefore the results obtained on single punch

presses do not directly correlate with tablets made on

rotary machines.

Benefits of Press Instrumentation

Among many benefits of press instrumentation, formu-

lation fingerprinting is perhaps the most obvious. Com-

pressibility and ejection profiles, as well as dissolution and

disintegration curves related to compression force, are

unique for each formulation and can be used as a batch

record. For process optimization, one can include com-

pression or precompression force and speed factors in

experimental design. Compactibility and ejection profiles

can be used for excipient and lubricant evaluation. Other

useful product development and optimization tools include

response surface, Heckel, and force–thickness plots.

Scientifically reliable process scale-up cannot be

achieved without instrumentation data providing scale-up

parameters such as dwell time, density, and energy of a

tablet.

In a pilot plant and on the production floor, proper

instrumentation can be used for press troubleshooting, to

warn about tooling irregularities, worn-out cams, sticking

punches, underlubricated dies, and so on. Finally,

instrumentation is widely used for tablet weight control.

Instrumentation for Formulation Development

Much of the current body of knowledge about

compaction properties of pharmaceutical materials

came from instrumented tablet presses.[52 – 56] Many

tablet properties, such as tensile strength (hardness) and

porosity can be predicted from force profiles.[57 – 59]

Work of compaction (a scale-up parameter) can be

obtained with proper instrumentation.[60,61] Information

about the plasticity of materials can be derived from

force–time curves.[62 – 64]

The phenomenon studied with the help of instrumenta-

tion is the so-called “lag time” (the time difference

between peak of compression and maximum punch

penetration). The extent of this lag is indicative of

compaction mechanisms of the powder being com-

pressed.[65,66]

Typical waveform

Let us have a look at the actual waveforms that one may

obtain from an instrumented tablet press (Fig. 7). The

black proximity switch trace that marks the beginning of a

revolution should be noticed. On this press, precompres-

sion and compression events coincide in time (they relate

to different punches, of course). They are followed by the

ejection and take-off.

Compactibility profile

When the average tablet hardness is plotted against the

average compression peak force, we get the so-called

compactibility profile that allows us to compare different

formulations or different processing speeds. Referring to

Fig. 8, which formulation is better? Well, formulation

No. 2 makes harder tablets for the same compression force,

and this would mean less wear and tear on the production

press is required to achieve desired hardness. On the other

Tablet Press Instrumentation8

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Page 9: Tablet Press Instrumentation

hand, if the hardness tolerance limits are exceptionally

narrow, the steeper slope of formulation No. 2 may be a

detriment.

Lubricant profile

A certain quantity of lubricant must be present in the

granulation to reduce the friction that occurs at the die wall

as the tablet is being ejected, as well as to prevent sticking

of the tablet to the face of the punches. Without

instrumented ejection cam and take-off bar, no objective

estimate of an optimal lubricant level is possible, and the

“best” formulation is usually the last one prepared.

The plot shown in Fig. 9 will help a formulator to

determine the optimal amount of lubricant. Obviously, one

would try to minimize the ejection force (again, to reduce

wear and tear on the ejection cam of the production press),

and yet to avoid the pitfalls of having too much lubricant in

the formulation.

Because of the natural association of lubricant proper-

ties with lipophilic materials, formulations containing high

levels of lubricant can show retarded dissolution of the

active ingredient and the slow dissolution rate could

adversely affect the in vivo bioavailability of the drug.

Lubricant study

Another important use of ejection force transducer is the

evaluation of lubricants (either different chemically, or

similar lubricants coming from different vendors).

As shown in Fig. 10, the preferred lubricant is No. 1 as

it results in a smaller ejection force. Early lubricant studies

are a must. When lubricant problems occur later on in the

scale-up process, corrective measures not only require

additional materials and development time, but may also

require a supplement of an approved new drug application

(NDA).

Response surface plot

Formulation and process optimization can be done

statistically with the use of experimental design for

estimates of the best processing parameters and excipient

Fig. 7 Typical compression, precompression, and ejection waveforms.

Tablet Press Instrumentation 9

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Page 10: Tablet Press Instrumentation

and lubricant levels. Controllable variables in tableting are

mainly the precompression and compression forces and

tablet press speed, as well as the formulation component

levels. Response variables include the ejection force,

tablet hardness and friability, dissolution rate, and drug

stability. The purpose of an experimental design is to

perform a series of experiments in order to determine some

levels of factors that will allow us to achieve an optimal

level of dependent variables. The experiments should be

designed so as to minimize effort and maximize statistical

reliability of the results. Published work in this area deals

mostly with response surface designs that produce a

predictor polynomial equation for each response variable

under consideration. A multidimensional surface is then

searched for the best ranges of factor variables that, when

plugged in the equations, result in the optimal value of the

Fig. 8 Compactibility profile.

Fig. 9 Lubricant profile.

Tablet Press Instrumentation10

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Page 11: Tablet Press Instrumentation

responses. In this plot (Fig. 11), the optimal (highest)

hardness is obtained when the compression force is in the

range 3000–4000 lb with as much MCC in the formulation

as possible.[67]

Compactibility study—elastic recovery

Many powders, especially with viscoelastic compaction

mechanism, such as starch or avicel, exhibit large degree

of stress relaxation (with time-dependent deformation).

If you monitor punch displacement and compression

force, you can make pretty accurate assessment of the

compactibility of your material. If LVDTs are attached to

both upper and lower punches, it is possible to actually

measure in-die thickness of the tablet at various

compression levels. In Fig. 12, one can see how the tablet

thickness rapidly decreases in the compression stage and

then gains some thickness during the decompression stage

of the tableting cycle. The degree of this increase in

Fig. 10 Lubricant study.

Fig. 11 Response surface plot.

Tablet Press Instrumentation 11

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Page 12: Tablet Press Instrumentation

thickness is indicative of the elastic recovery as the

pressure is removed from the tablet.

Elastic recovery and work of compaction were studied

extensively using instrumented tablet presses.[68]

Compactibility study—Heckel plot

In 1961 Heckel[69,70] postulated a linear relationship be-

tween the relative porosity (inverse density) of a powder

and the applied pressure. The slope of the linear regression

is the Heckel constant, a material-dependent parameter

inversely proportional to the mean yield pressure (the

minimum pressure required to cause deformation of

the material undergoing compression). Large values of the

Heckel constant indicate susceptibility to plastic defor-

mation at low pressures, when the tablet strength depends

on the particle size of the original powder. The intercept of

the line indicates the degree of densification by particle

rearrangement (Fig. 13).

TABLET PRESS INSTRUMENTATION FORPROCESS TROUBLESHOOTING

Typical problems in tableting include weight variation,

capping, lamination, tooling irregularities, die binding,

picking, and sticking. Most of such problems can be

detected and/or resolved using proper instrumentation.

Upper and Lower Compression

Fig. 14 shows a typical set of upper and lower compression

profiles. One can see that the lower trace is smaller than the

upper. On a single station press, only the upper punch is

usually moving, and the difference is caused, mainly, by

the friction of the compressed powder inside the die.

On a rotary press, both punches are moving and

therefore the friction of the punches inside the turret and

the die causes the difference. The lower punch fits the

turret with a larger standard clearance compared to the

upper punch. In addition, the lower punch is never leaving

the die, while the upper punch leaves and enters the die

with each stroke. This results in a comparatively better

alignment and lower friction. The close fit of the upper

punch does not allow it to penetrate the die smoothly and

this can cause the increase in friction. Thus, an excessive

difference between the two peaks may indicate an

underlubricated die or some punch misalignment problem.

Histogram of Punch Performance

Similar irregularities in punch tolerances become even

more visible on a bar histogram where each bar

corresponds to peak force produced by each punch

(Fig. 15). As the new revolution arrives, the bar lengths

Fig. 12 Compactibility study—elastic recovery.

Fig. 13 Heckel plot. Fig. 14 Upper and lower compression force vs. time.

Tablet Press Instrumentation12

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Page 13: Tablet Press Instrumentation

are adjusted. If a particular bar persists in being taller or

smaller than the rest, it means the presence of a long or

short punch.

Press Monitor—Real-Time Screen

On this real-time screen (Fig. 16), one can clearly see

that there is an abnormal ejection event in the first station

after the proximity switch. This is a clear indication of a

sticking punch or a similar problem. In addition, the first

compression peak is somewhat taller than others. This

may be caused by a long punch.

TABLET PRESS INSTRUMENTATIONFOR PROCESS SCALE-UP

Scale-Up Factors

One of the main practical questions facing formulators

during development and scale-up is: Will a particular

formulation sustain the required high rate of compression

force application in a production press without lamination

or capping? Usually, such questions are never answered

with sufficient credibility, especially when only a small

amount of material is available and any trial and error

approach may result in costly mistakes along the scale-up

path.[71]

Fig. 15 Histogram of compression force per punch.

Fig. 16 Real-time screen.

Tablet Press Instrumentation 13

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Page 14: Tablet Press Instrumentation

As formulations are moved from small-scale research

presses to high-speed machines, potential scale-up

problems can be eliminated by simulation of production

conditions in the formulation development lab. One way to

eliminate potential scale-up problems is to develop

formulations that are very robust with respect to

processing conditions. A comprehensive database of

excipients detailing their material properties may be

indispensable for this purpose. However, in practical

terms, this cannot be achieved without some means of

testing in production environment and, because the initial

drug substance is usually available in small quantities,

some form of simulation is required on a small scale.

Studies of tableting process on a class of equipment,

generally known as compaction simulators, are designed

to facilitate the development of robust formulations.

However, simulators are rarely used to simulate tablet

presses for reasons that will be explained later.

In any process transfer from one tablet press to another,

one may aim to preserve mechanical properties of a tablet

(density, and, by extension, energy used to obtain it) as

well as its bioavailability (e.g., dissolution that may be

affected by porosity). However, a formulation that was

successfully developed on a single station or small rotary

press may not stand up to the challenges of scale-up

because tablets that were meeting all specifications in the

lab or clinical studies may exhibit capping or lamination at

higher speeds.[72,73]

Compression force magnitude and the rate of force

application are the most important variables in tableting

scale-up.

Force factor

The compression force is the dominant factor of the

tableting process. It is directly related to tablet hardness

and friability, and is correlated with the phenomena of

lamination and capping.

It was also shown to have effect on disintegration times

and dissolution profile.

Speed factor

As the punch speed increases, so does the porosity of

tablets and their propensity to capping and lamination. The

tensile strength of compacts tends to decrease with faster

speeds, especially for plastic and viscoelastic materials,

such as starch, lactose, avicel, ibuprofen, or paracetamol.

Such materials have the tendency to cap or laminate at

higher speeds.[74 – 88]

The notions of dwell time and contact time, to be

discussed in detail later, are the common indicators of

press speed and the rate of force application.

Force profile factor

In addition to the level of force and the rate of force

application, the shape of the compression force vs. time

curve is of a paramount importance because it directly

affects tablet properties such as hardness and friability.

It is a known fact that the compression part of the

compression cycle (during the “rise time” of the force–

time profile) is 6–15 times more important than the

decompression part as a factor contributing to capping and

lamination. On the other hand, reducing the decompres-

sion part of the cycle results in the increase of tablet

hardness by reducing the extent of elastic recovery.[89]

Alternatively, reducing the compression part of the cycle

results in no change of tablet strength for viscoelastic

materials and increased hardness for brittle materials.

Other Considerations

Numerous other factors may affect the scale-up process.

The quality of the measurements, variation in tooling,

powder properties, and tablet weight are some of those

factors.

. Instrumentation grade.

. Measurement of speed.

. Measurements of mechanical strength.

. Tooling variation.

. Powder flow variation.

. Excipient/raw material variation.

. Tablet weight variation.

Dwell Time and Contact Time

Matching tablet press speed (rpm) of the research and

production presses has, of course, no meaning, because of

different number of stations and pitch circle diameter. It is

vital, therefore, to translate the rpm into dwell time or

contact time.

Many investigators have reported the effect of dwell

times and strain rate sensitivity on the compaction of

various excipients, especially viscoelastic materials.[90 – 94]

There are at least two definitions of dwell time in practice

today.

Functional definitions

Functionally, the effective dwell time (EDT) at 90% level

can be defined as the time it taken by the force–time curve

Tablet Press Instrumentation14

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to traverse the 90% of the peak height. Likewise, the

effective contact time (ECT) is the time between points at

10% of the peak height. The shape of the force curve

depends, as we know, on the deformation mechanisms of

the powder and therefore, all other variables being equal,

EDT and ECT will be different for brittle and plastic

materials. Although somewhat useful for material

characterization, such variables should not be confused

with the universally accepted definitions of contact time

(time of contact) and dwell time (time of immobility).

Mechanical definitions

Mechanical Definitions of dwell and contact times

disregard material properties and concentrate on press

and punch geometry (Fig. 17). Contact time can be defined

as the time the punch is in contact with the compression

wheel. Dwell time is defined as the time the flat portion of

punch head is in contact with the compression wheel (time

at maximum punch displacement, or time when the punch

does not move in vertical direction). In dwell time

calculations, the length of the punch head flat and

horizontal component of punch speed (as determined by

RPM and pitch circle diameter) are used. In case of a round

head tooling, the dwell time, as defined here, is zero. But it

should be kept in mind that mechanical definition is given

here as a convention, a yardstick, or a common measure, to

compare press speeds for different presses, and its absolute

value is meaningless. A proposed convention to quantify

linear speed of a press is to use an Industrial Pharmaceu-

tical Technology (IPT) Type B tooling with a known punch

head flat as a standard for press speed comparisons.

In what follows, we will use the mechanical, rather than

functional, definitions because they serve as an objective

material-independent measure of compaction speed.

Dwell time comparison for different presses

Comparing the dwell time ranges for a number of presses

can be a gratifying experience. Here one can see that even

for the same brand name, there is a wide distribution of

ranges. It has to be noted that proper scale-up will be

possible only when the ranges overlap. Dwell time range

may also be used to classify or identify tableting equipment.

The dwell time ranges vary considerably in various tablet

presses. As shown in Fig. 18, Manesty Betapress is

positioned well within the range of production speeds of the

high-speed presses. That is, probably, why this press is

often used for R&D work. On the other hand, small presses

such as Korsch PH106 or Piccola do not even come close to

benchmark production speeds of 6 msec–15 msec in terms

of dwell time. The MCC Presstere can reach the

production dwell times while making one tablet at a time.

Dwell time vs. production rate

For a benchmark production speed of 100,000 tablets per

hour (Fig. 19), dwell time distribution follows an inverse

power relationship, which is expected because dwell time

is a reciprocal function of the press speed. In general, all

production presses should be qualified with respect to

dwell and contact times per benchmark output. Ideally,

product development must be done on a laboratory press

that can match (in terms of the dwell time) the target

production output.

Dimensional Analysis of Tableting Process

Dimensional analysis is a method for producing dimen-

sionless numbers that completely characterize the process.

It is widely used in many areas, including chemical

engineering and pharmaceutical industry.[71] Because all

Fig. 17 Dwell time and contact time—mechanical definitions.

Tablet Press Instrumentation 15

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the dimensionless numbers necessary to describe the

process in similar systems must have the same numerical

value,[95] matching such values on different scales is a sure

way to success in any scale-up operation. This dimension-

less space in which the measurements are presented or

measured will make the process scale invariant.

In tableting applications, the process scale-up involves

different speeds of production in what is essentially the

same unit volume (die cavity in which the compaction

takes place). Thus, one of the conditions of the theory of

models (similar geometric space) is met. However, there

are still kinematic and dynamic parameters that need to be

investigated and matched for any process transfer.

Scientifically sound approach would be to use the

results of the dimensional analysis to model a particular

production environment to facilitate the scale-up of

tableting process, by matching several major factors,

such as compression force and rate of its application

(punch velocity and displacement) in their dimensionless

equivalent form.[96]

TABLET PRESS AND COMPACTIONSIMULATORS

It can be seen that, as a rule, tablets are formulated at

speeds that are very slow compared to production. If

Fig. 18 Dwell time comparison for different presses.

Fig. 19 Dwell time vs. production rate.

Tablet Press Instrumentation16

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simulation of a production press is required to minimize

the scale-up effort, some way of speeding up the tableting

process in development is required. Once the linear speed

of the punch is attained, the rate of force application (i.e.,

the instantaneous change in compression) should also be

matched. This is, of course, an infinitely more difficult task.

Hydraulic Compaction Simulator

A small number of devices known as compaction

simulators exist in the world. Invented more than 20 years

ago, they become popular in basic compaction research.

A wealth of studies have been generated in the last

20 years.[97 – 117]

Compaction simulators (Fig. 20) were designed to

mimic the compression cycle of any prescribed shape by

using hydraulic control mechanisms that are driving a set

of two punches (upper and lower) in and out of the die. All

hydraulic compaction simulators are similar in design and

construction. A compaction simulator consists of several

main units: the load frame (column supports and cros-

sheads with punches), the hydraulic unit (pumps and

actuators that move the crossheads), and the control unit

(electronic console and computer). Usually, a simulator

accepts F tooling only, but can be retrofitted to use

standard IPT B tooling. Under computer control, the

hydraulic actuators maintain load, position, and strain

associated with each punch.

The simulation can be achieved by one of the two

procedures: matching either the force (load control) or the

movement of punches (position control) at any given

moment of time. Thus, when running a simulator, one has

a choice: to mimic the force/time path (compression

profile) or the motion of the punches (punch displacement

curves). It is impossible to mimic both at the same time on

any hydraulic compaction simulator.

Load control profile

Matching the force–time profile of a production tablet

press is the primary goal of any tablet press simulation.

However, the rate of force application and the shape of

the resulting signal are not usually known in advance.

The compression profile (force vs. time) is impossible to

calculate theoretically because it has a different shape for

different materials and tooling.

Using an instrumented punch to collect force data is

cumbersome because it is limited to a particular punch size

and shape. Recalculation to pressure values is not always

adequate. One can, however, monitor and record force

waveform from a properly calibrated R&D grade

compression transducer. Once the production press

brand, model, speed, and tooling are specified, a waveform

can be recorded and then fed into hydraulic simulator.

This approach is impractical for formulation develop-

ment work because one would need to record force

waveform on a rotary press using formulation similar to

the one being developed. Usually, there is no such powder

available and the actual formulation being developed is

available in limited quantities.

Position control profile

Because load control profiles are not practical, users of

hydraulic compaction simulators overwhelmingly prefer to

utilize punch displacement profiles in hope that, once the

punches are forced to move in the same pattern as in the

production press, the force–time curve will follow. For

example, a recently built laboratory compaction simulator

does not have a force control functionality at all.[118]

There are three possible sources of the punch position

trace:

. Prerecorded data.

. Artificial profiles.

. Theoretical profiles.Fig. 20 Schematic depiction of a compaction simulator.

Tablet Press Instrumentation 17

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To obtain a position control profile from any tablet

press, one has to record the movement of the punches

using LVDT. Besides the technological challenge that this

objective may present, the punch movements on a press

depend on many factors, including brand name and model

of the press, speed of the turret, shape of punches and die,

size and shape of the tablet, and most importantly,

compaction properties of the powder. The problem with

this is that data from production presses are inevitably

obtained using material other than the one being

developed. It is a vicious circle: the profiles before

developing a formulation and the formulation before

obtaining punch displacement profiles are needed.

Many compaction studies were done on compaction

simulators using artificial punch displacement profiles, for

example, the so-called “single-ended” profile, i.e. when

the lower punch is stationary (like in a single station

press). Other studies were using a “saw tooth” profile, i.e.,

a constant speed profile where punch displacement speed

is constant at any given time interval under load. It is

obvious that such profiles have nothing to do with

simulation, although they provide a degree of uniformity

for basic compaction studies. The very name “compaction

simulator” is a misnomer as is acknowledged by a number

of researchers in the field. The machine is best described as

a compaction research system because it is well suited for

the basic compaction studies (densification and bonding

properties of materials).

To simulate tablet presses, compaction simulator users

most frequently employ the theoretical position control

profiles. Theoretical path is calculated from the geometry

of the press and punches, using the radius of the com-

pression roll, the radius of the curvature of the punch head

rim, the radius of the “pitch circle” (distance between

turret and punch axes), and the turret angular velocity.[119]

The resulting sinusoidal equation is used in order to

“simulate” punch movement in a tablet press.

In practice, theoretical and actual punch displacement

profiles on a rotary press have very little in common because

the theoretical profile does not account for several mecha-

nical factors, such as punch head flat. Moreover, the punch

movement equation was derived for a punch moving in and

out of an empty die. The effect of material resistance to

pressure and elastic recovery is not accounted for in the

equation. The discrepancies between the calculated and

real punch movements are rather striking.[120 – 122]

In addition, it was shown that the lower and upper

punches may not move synchronously. Moreover,

maximum force does not coincide in time with the

minimum punch gap.[123] These and other considerations

(press deformation, contact time, etc.) make the effort of

simulating a production press on a hydraulic compaction

simulator rather impractical. That is why, to quote from a

paper by Muller and Augsburger,[124] “Although compac-

tion simulator have been designed to mimic the

displacement time behavior of any tablet press, they

rarely have been used in that fashion.”

Literature sources reporting the use of compaction

simulators in simulating actual tablet presses are rather

scarce. Some studies suggest that, for whatever reason,

tablets made on a Manesty Betapress were significantly

softer than those made on a compaction simulator using the

theoretical Betapress punch displacement profiles.[120,125]

To summarize, one can say that hydraulic compaction

simulators are ideally suited for basic compaction research

but are not very practical for simulation of production

presses.

Tablet Press Replicator: The Presstere

Recently, a new type of machine was introduced to mimic

production presses on a small scale. Known under a brand

name of “Presster”—kind of an agglomeration of the

words “press,” “presto,” and “tester”—this machine can be

classified as a mechanical compaction simulator.

The Presstere is a high-speed single station press that

is also a tablet press simulator (Fig. 21). It was designed to

simulate production presses without any use of hydraulic

controls, and, consequently, there is no need to feed in any

artificial, theoretical, or prerecorded punch displacement

profiles. Built around a linear carriage that moves a set of

punches and a die between two compression rolls, it can

mimic press geometry by matching the compression

wheels match press speed using a variable speed motor

drive match tablet weight and thickness by adjusting depth

of fill and the distance between the rolls match tooling by

installing standard IPT or any special tooling.

Thus, using mechanical similarity, all of the scale-up

fact are matched, namely, the compression force, the

speed, and the shape of the force profile. To use Presster,

first a production press to be simulate should be selected,

and the compression wheels with a matching diameter

should be installed. Then, production speed should be

selected in terms of tablets per hour, RPM, or dwell time.

The Presstere will mimic the selected production press

speed and compression force profile and will allow us to

make one tablet at a time.

As a high-speed single station press, mechanical

compaction simulator will be able to plot compressibility

profiles, Heckel graphs, calculate work of compaction, and

virtually any other imaginable variable that is of interest to

formulators. Tensile strength of tablets made on a

Betapress and The Presstere was similar.[126]

Tablet Press Instrumentation18

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Page 19: Tablet Press Instrumentation

Precompression and ejection steps of the tableting cycle

can be included in simulation. Some current limitations of

Presster should be pointed out: It will neither follow any

artificial punch movement profile, nor will it address, at

least in its present implementation, the issues of feeding

and die fill at high speeds, or speed-related temperature

fluctuations.

PRESS INSTRUMENTATION AND CONTROLON THE PRODUCTION FLOOR

Tablet Weight Control and Tablet ForceControl

To keep tablet weight within the prescribed tolerance

limits, the required instrumentation includes compression

transducer and several proximity switches for station

identification and pinpointing the compression event.

Tablet weight controller can be just one, albeit a major,

unit of a larger press automation system. Press automation

system may include:

. Tablet weight control.

. Material handling interface.

. Feeding system.

. Collection system.

. Packaging system.

. Supervisory control (SCADA) station.

The latter can be a computer positioned on the

supervisor’s desk that monitors the performance of each

press on the production floor, with timely status report for

each batch.

There are many reasons why it is imperative to control

tablet weight variation:

. Production costs are lowered because there is less

waste.

. Productivity is increased because there is a better

equipment utilization.

. Batch-to-batch variability is minimized for obvious

reasons.

When the cost of each out-of-spec wasted tablet is

significant, the savings produced by weight control

quickly add up. Product quality is improved when there

is less of a chance to get an out-of-spec tablet into the

acceptable batch. Last, but not least, is the improved safety

because the automated process requires less human

intervention.

Fig. 21 Tablet press replicator: The Presstere.

Tablet Press Instrumentation 19

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Page 20: Tablet Press Instrumentation

Control mechanisms

For constant tablet thickness, in a small target area of

tablet weight, compression force is directly proportional to

tablet weight. Force control systems maintain compression

force within prescribed limits by adjusting the depth of fill

cam. The limits are established empirically for each

formulation recipe.

Alternatively, a weight control system would require

an expressed correlation between force and tablet weight.

A few tablets at different force levels can be made to

correlate the resulting tablet weights with the force values.

Next, one can express tablet weight tolerance limits in

terms of the compression force. The weight control system

can adjust the dosing to keep the tablet weight within the

desired limits. For this control theory to work consistently,

one needs to recalibrate force–weight relationship

periodically, as the powder properties and tablet

mechanical condition can vary in time.

Control functions include alarm and shutdown (when

any individual force peak or revolution average exceeds

preset limits), force or weight control (usually done on

revolution average only), and rejection of out-of-spec

tablets. With a mechanical gate, usually several tablets are

rejected at a time, with the bad tablet being rejected along

with the adjacent good tablets. With a fast pneumatic–air

stream rejection mechanism, the control system can

pinpoint and reject one bad tablet only.

Control criteria

Control decisions are usually done as follows:

1. Adjust depth of fill cam if revolution average is

outside some redefined acceptable limits.

2. Reject each tablet that exceeds individual limits or

if the press speed slows down beyond some level.

3. Sound an alarm if the same station repeatedly

produces bad tablets or if revolution average

exceeds alarm limits.

4. Shut down the press if any tablet is made with a

force exceeding the shutdown limits, or if

revolution average is outside the shutdown limits.

Control algorithms

One-point control is a description of a control when any

deviation of the compression force from a preset target

level results in a corrective action of the dosing cam. This

action can be proportional (P) to the deviation from the

target, or it could be correlated with the integral (I) of

the deviation over some time, or it could be tied in with the

rate of change (D, for derivative) of the compression force.

This would correspond to proportional, integral, or

derivative control types, respectively. There also can be

a combination of the control types. Thus, one can have P, I,

P þ I, P þ D, and P þ I þ D control algorithms.

Alternatively, a two-point control is enacted when the

compression force is outside an acceptable band outlined

by the upper and lower tolerance limits. Thus, there are

separate control limits, rejection limits, alarm limits, and

shutdown limits, and no respective action is taken when

the signal is inside these limits.

Strictly speaking, one-point control can be viewed as a

special case of the two-point control when the bandwidth

of the control limits is tightened to approach zero.

Control Systems

Original equipment manufacturer (OEM) controlsystems

Almost each tablet press manufacturer offers a system that

is designed to control the press. Some of these systems are

very sophisticated devices that monitor and control a vast

array of tableting functions. If, however, there are several

brand names on the production floor, any standards in the

control system implementation for different manufacturers

should not be expected. Likewise, software interfaces

exhibit quite a range of user-friendliness.

In one brand name press, tablet weight control is

achieved by regulating the dosing cam based on powder bed

thickness in the precompression cycle. This clever approach

is possible because precompression force is kept relatively

constant by means of pneumatic compensating mechanism.

Under these conditions, tablet weight is directly pro-

portional to thickness. The subsequent compression cycle

can be done to constant thickness, like on any other press.

Generic control systems

Analternative toOEM control systems isgeneric controllers

that may offer plug-in compatibility with the brand name

controllers and may provide a degree of standardization.

However, such generic controllers may lack the

degree of sophistication and versatility of the controllers

that are made by the press manufacturers. One thing to

keep in mind is that not all control systems are created

equal, but all control systems use the same principles.

A decent tablet weight control system should be based

on product recipes, provide instant display of compression

force distribution, control charts and batch reports on

Tablet Press Instrumentation20

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Page 21: Tablet Press Instrumentation

demand, archiving data for subsequent analysis or

documentation, give some measure of standardization,

be fully compliant with current validation requirements,

and provide a multilevel security, e.g., password

protection for operator and supervisor when they need to

change recipes, etc. Some examples of displays, available

to operators of instrumented production presses equipped

with controllers, follow.

Recipe example

In Fig. 22, an example of a typical control recipe with

dosing cam adjustment, rejection, alarm, and shutdown

limits expressed as a percent deviation from the target

tablet weight is shown. The software then converts all

values into the corresponding compression force levels for

control purposes.

Bar histogram

This chart is similar to one used in tablet press monitoring

for press troubleshooting (Fig. 15). It is vital for any

production press operator.

Control chart

Control chart is a simple graph of peak compression force

vs. time. Each point on the chart corresponds to the

Fig. 22 Recipe example.

Fig. 23 Statistical process control X-bar chart.

Tablet Press Instrumentation 21

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Page 22: Tablet Press Instrumentation

average of N tablets made, with N ranging from 1 to

several revolutions. The horizontal lines would indicate

the control limits.

Statistical process control chart

Statistical process control (SPC) chart (Fig. 23) of the

averages is another “must have” real-time display. Each

point on the chart represents a revolution average of the

compression forces or corresponding tablet weights.

The limit lines are calculated at one standard deviation

of the mean, and there are certain rules that are used to

determine when and if the process gets out of control.

These rules are available in any textbook on the SPC.

ACKNOWLEDGEMENT

Selected excerpts and figures from M. Levin, “Tablet Press

Instrumentation for Product Development, Process Scale-

Up and Production Quality Control, Education Anytime,

CD-ROM Short Course, AAPS 1999” are reprinted with

permission.

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Tablet Press Instrumentation24

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Tablet Press Instrumentation26

©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016