Professional Documents
Culture Documents
Compression/Compaction
By Dr. Keith Marshall
Table of Contents
Compression/Compaction ..........................................................................................................1
Table of Contents ....................................................................................................................1
General Introduction................................................................................................................4
The Pros and Cons of Tablets.............................................................................................4
The Sophisticated Tablet.....................................................................................................4
Some Important Properties of Powders Intended for Tablets ................................................5
Deformation.........................................................................................................................5
Effect of Massive Extended Forces ....................................................................................7
Compression ...................................................................................................................7
Consolidation ..................................................................................................................8
Die Compaction (Tableting) .....................................................................................................8
Simple Tablet Press Cycle...................................................................................................8
System Geometry .........................................................................................................11
Force-Time Profiles .......................................................................................................11
Compressibility..................................................................................................................12
Heckel Plots ..................................................................................................................12
Density Distributions in Compacts................................................................................13
Frictional Effects............................................................................................................14
Load Removal and Tablet Ejection ...................................................................................15
Removal of Applied Load..............................................................................................15
Ejection..........................................................................................................................15
Consolidation Potential .....................................................................................................16
Compaction Force Versus Tablet Strength ...................................................................16
Energy Involved in Compaction ....................................................................................17
Work of Compaction .........................................................................................................18
Analysis of Force-Displacement Curves .......................................................................18
The Tableting Process ...........................................................................................................19
Introduction to Tablet Presses ..........................................................................................19
Tablet Machine Design ......................................................................................................20
Single-Station Presses ..................................................................................................20
Multi-Station Presses ....................................................................................................20
Contemporary Tableting Process..........................................................................................23
High Production Rates ......................................................................................................24
High Turret Speed .............................................................................................................24
Precompression ............................................................................................................25
Cams .............................................................................................................................25
1
Feeders..........................................................................................................................26
Lubrication.....................................................................................................................27
Increased Number of Stations ..........................................................................................27
Turret Web .....................................................................................................................28
Multi-Sequence Presses ...................................................................................................28
Multi-Tipped Tooling..........................................................................................................28
Ancillary Equipment ..........................................................................................................29
Tablet Tooling ....................................................................................................................30
Punches.........................................................................................................................30
The Hob.........................................................................................................................30
Matched Tooling............................................................................................................30
Inspection......................................................................................................................30
Tablet Problems.....................................................................................................................31
Release Profile...................................................................................................................31
Weight Variation.................................................................................................................31
Content Uniformity ............................................................................................................32
Mechanical Strength Problems .........................................................................................32
Capping and Lamination...............................................................................................33
Chipping ........................................................................................................................34
Stress Cracking .............................................................................................................34
Picking...........................................................................................................................34
Rate of Compaction (Press Speed)...................................................................................35
Effects of Compaction Rate..........................................................................................35
Problems of Scale-Up .......................................................................................................36
Tablet Press Selection ...........................................................................................................37
Some Recent Trends .............................................................................................................38
Instrumented Tablet Machines (ITM’s) ..................................................................................38
Contemporary Practice .....................................................................................................38
ITM’s in Research and Development ................................................................................39
Significance of Press Signals............................................................................................39
Ejection Forces..............................................................................................................39
Lower Punch Pulldown Forces .....................................................................................40
Upper Punch Pullup Forces ..........................................................................................40
Sweep-Off Forces .........................................................................................................40
Feeder Paddle Shaft Torque .........................................................................................40
Commercial Instrumentation Packages ............................................................................41
Weight Monitoring in Production Presses.........................................................................41
Special Tablet Types..............................................................................................................42
Layered Tablets .................................................................................................................42
Compression-Coated Tablets ...........................................................................................42
Effervescent Tablets ..........................................................................................................43
Chewable Tablets ..............................................................................................................44
Lozenges ...........................................................................................................................44
2
Tablet Strength ......................................................................................................................44
Tablet Failure Tests............................................................................................................44
Breaking Force ..............................................................................................................44
Tensile Strength.............................................................................................................45
Surface Abrasion...........................................................................................................46
References ............................................................................................................................46
Bibliography ..........................................................................................................................46
3
General Introduction
Tablets comprise the largest group of • High level of patient acceptability
delivery systems for all prescribed and and compliance
over-the-counter medications, and therefore,
warrant detailed consideration of their Among the few disadvantages of tablets
design, development and manufacture. as a dosage form is the possibility for
The main objective of this chapter is to bioavailability problems, due to the fact that
outline contemporary approaches to the dissolution must precede absorption of the
development and production of these active ingredient. This requires that tablets
important dosage forms. The underlying for immediate release of medicament
basic principles of tablet technology and should disintegrate rapidly after ingestion to
their pragmatic applications will be reviewed. facilitate solution of the active component.
Compressed tablets may be defined as drug In addition, there is the chance that GI
delivery systems intended to be taken by irritation could be caused by locally high
mouth and made up of a single solid body. concentrations of medicament. Also, from
a patient standpoint, a small proportion of
Some of the most common types include: people do have difficulty in swallowing
• Immediate release, coated or uncoated tablets, and so size and shape become
(swallowable) important considerations.
• Modified release, coated or uncoated
(swallowable) The Sophisticated Tablet
• Effervescent (dissolved/suspended in
water before drinking) It should be realized that tablets are rightly
• Chewable (chewed before swallowing) regarded as complex drug delivery systems,
• Lozenge (dissolved slowly in the mouth) and that to trivialize their design, develop-
ment and manufacture is certain to invite
The most popular of these is the immediate significant problems at some stage in
release tablet, intended to be swallowed development or during product life.
whole, and release the medicament rapidly
in the stomach. With this philosophy in mind, it is obvious
that it will be important to begin by
The Pros and Cons of Tablets considering the important and relevant
properties of the materials used to manufac-
Some of the reasons for the popularity ture a tablet. There is no doubt that many
of tablets include: tableting problems arise because of failure
to pay attention to the properties of the raw
• Ease of accurate dosage, patient materials, and/or appreciate how they are
takes one or more discrete units likely to behave when they are subjected
• Good physical/chemical stability, to the tablet machine cycle.
because of low moisture content
• Competitive unit production costs
• Elegant distinctive appearance,
easily identifiable
4
Some Important Properties of Powder Intended for tablets
During the manufacture of tablets, bulk perhaps better expressed as the force
powders or granules will be subjected to per unit area over which it acts, i.e., a
significant, and in some cases, massive pressure. These latter forces are sometimes
applied mechanical loads. Their behavior considered at points in the system and are
under these circumstances may be the referred to as the stress on that particular
major factor controlling the success or region of the material. At least three types
failure of the manufacturing operation of stress may be distinguished, as shown
involved. in Figure 1. The relative change in geometry
is called strain. In the present context of
Deformation particular interest are the strains caused
by application of a compressive stress as
All solid materials change in shape/volume shown in Figure 2.
when subjected to mechanical forces,
Stress = Force
Area
Compressive
Strain
Stressed condition
= ho - h
ho
5
There are several ideal model behaviors At the other extreme, the strain caused by
that facilitate understanding of what may the applied stress may continue to increase
be occurring in the tableting materials when with time until the load is removed (see
under load. When force is first applied to the Figure 3). At this point, there is no tendency
material in the die of the tablet press, there to recover to the original geometry.
will be some degree of repacking of the Therefore, the amount of strain is time
particles, leading to a higher bulk density. dependent and is not spontaneously
This is usually limited to the initial low load reversible. This viscous response to
region and is quickly superceded by other loading is called plastic deformation.
phenomena.
In practice, most solids demonstrate
One possibility is that application of an properties which lie between these two
increasing compressive load results in extremes and are described by models
failure of the structure and the particle combining them, resulting in visco-elastic
breaks into two or more pieces. This behavior. The simplest combination of these
behavior, known as brittle fracture, is found models that might equate to a real powder
in such excipients as dicalcium phosphate, particle is illustrated in Figure 4. Note that in
some sugars, and in some active ingredi- this case there will be some degree of time
ents. Another possibility is that the material dependency to the deformation process,
behaves like a spring, and the application and if the solid material is not given time to
of an instantaneous stress causes a deform, then the solid will have to react in
matching instantaneous strain response, some other way. This could be a major
with immediate total recovery to the original problem as the process is scaled up to
geometry on removal of the load, as shown faster presses with less time available to
in Figure 3. make each individual tablet. Note also that
there will be some time dependent recovery
Figure 3: Elastic Versus Plastic Deformation after the load is removed. If a sufficiently
strong tablet has not been formed at the
Strain Elastic deformation point of maximum loading, then the recovery
may result in failure of the tablet structure,
or at least in localized regions of it.
n
io
at
rm
fo
de
tic
as
Pl
Stress on Time
6
Figure 4: Stress-Strain “Real” Particle
Strain
Elastic
Plastic plus
Visco-elastic Visco-elastic
Elastic
Stress On Time
7
Consolidation surfaces, which the applied force will ensure
are kept in close proximity. Of course, as
In tableting, consolidation is due mainly compaction proceeds, some of the bonds
to the close approach of particle surfaces that are formed will be broken to facilitate
to each other, facilitating intermolecular further compression. Nevertheless, the
bonding by van der Waals forces, for overall effect is usually an increasing
example. Alternatively, since the entire number of bonded areas.
applied load must be transmitted via
particle-particle point contacts, considerable It is also important to appreciate that having
pressures may develop at these points. This compacted the material, the load must be
can cause frictional heating with a possibility removed and the tablet has to be ejected
of localized melting, especially if a low from the die. This will introduce new stresses
melting point solid is present. The resultant into it. Therefore, at the point of maximum
relief of the local stress at the point contact applied load, a structure which is strong
would lead to resolidification, forming a enough to accommodate the new stresses
bridge between the particles. must be developed. In other words, the
mechanical strength of the tablet will be
It follows that the consolidation process a reflection of the number of surviving
will be influenced by: bonds after it leaves the press.
• The chemical nature of the surface On the other hand, plastic deformation is
• The extent of the available surface not spontaneously reversible, but is time-
• The presence of surface contaminants dependent, and therefore, tablet press
• The intersurface distances speed may be a major factor. However,
continuing plastic deformation during
It is easy to see how the last three of unloading and ejection may relieve the
these factors might affect the compaction induced stresses during these parts of
process, since if large, clean surfaces can the tableting cycle, and thus avoid
be brought into intimate contact, then structural failure of the tablet.
bonding should occur. Brittle fracture (and
plastic deformation) should generate clean
All tablet presses employ the same basic Simple Tablet Press Cycle
principle. They compact the granular or
powdered mixture of ingredients in a die It will be convenient to study the basic
between two punches; the die and its process by reference to this simplest
associated punches being called a station tableting cycle, i.e., that of a single-station
of tooling. The simplest arrangement is (eccentric) press. In such a system, the cycle
illustrated in Figure 5. of punch movements will be as illustrated in
Figure 6, and these will generate the typical
force profiles shown in Figure 7.
8
Figure 5: Simple Tableting System
Material
Lower punch
Lower punch
carrier
Lower
punch
Filling Compacting
Ejecting
9
Figure 7: Cycle of Punch Movements
0
0 40 80 120 160 200 240 280
Time [msec.]
It is important to appreciate what forces • That transmitted axially to the lower
are acting during tableting because punch, FL
changes in the applied forces may well • That transmitted axially to the die-wall,
swamp the effect of other variables. FD
Therefore, formulation development must • That transmitted radially to the die-wall,
be carried out under conditions where the FR
maximum load applied to the tablet mass
is accurately known. In a simple tableting and since there must be an axial balance
event, mechanical force is applied to the of forces, then:
upper punch, FU, which goes through the
cycle, and produces the reaction forces FU = FL + FD
shown in Figure 8:
10
Figure 8: Forces Acting in Simple System
Radial die
wall force Lower punch
force
11
Figure 9: Typical Force-Time Trace
Peak force
Dwell time [100%]
[90%]
Force
Time
More specifically, if the compaction event include a term for the initial porosity of
is carried out slowly, then the ratio of the the mass, just before load is applied. This
area to peak force, over the area from peak means that for a given applied force, the
force, gives an approximate indication of final porosity depends on the initial porosity.
the extent of the elastic recovery. The However, there is no universal equation that
two areas should be equal if the material describes the behavior of a wide range of
is perfectly elastic, and the ratio will be materials over the entire force profile.
larger the more brittle fracture or plastic
deformation dominates the behavior of Heckel Plots
the material.
Among these many equations relating
Compressibility porosity to applied load is that usually
credited to Heckel1 which has been widely
A finite end to the compressional process used in tableting studies, producing data
occurs when the air spaces are completely similar to that shown in Figure 10. It is based
eliminated. There is frequently an inverse upon an equation involving the assumption
relationship between the residual porosity that the material behaves in an analogous
and the strength of the compact. This way to a first order reaction, where the
changing porosity of the tablet mass pores are the reactant, i.e.:
during the tableting cycle is a convenient
and valuable means of following the degree Ln E-1 = KyP + Ko
of compression achieved as a result of
the applied force. Several workers have where Ko is related to the initial repacking
attempted to analyze the porosity versus stage, or function of Eo, and Ky is a
force plots, and many equations have been material-dependent constant inversely
proposed for the force region in which most proportional to its yield strength Py, by
tablets are produced. All of these equations the following;
12
Py 1 / Ky Figure 10: Examples of Heckel Plots
13
Figure 11: Density Distribution Within a Tablet
? less dense
region
14
Experimental results demonstrate that in maximum penetration into the die, the
unlubricated systems the exact relationship tablet may expand due to elastic recovery
is widely variable, but there is a definite and visco-elastic recovery. The former is a
trend for die-wall lubrication to result in very rapid process, while the latter may even
constant FL/FU ratios. Indeed the ratio has continue after the tablet is ejected from the
been termed the coefficient of lubricant die.
efficiency, the so-called R value, but is
dependent on the H/D ratio and is not Ejection
always linearly related to FU.
The process of ejecting tablets (from the die)
Some materials also tend to adhere to introduces a new set of stresses into them
punch faces, and thus a third group of and the tablet structure must be able to
additives is recognized that minimize this withstand them. The practice of including
phenomena and are called anti-adhesives. a lubricant in tablet formulations to reduce
Talc is a common example. friction at the die wall plays a major role in
minimizing the potential for failure of the
Load Removal and Tablet Ejection tablet structure during ejection.
15
Figure 12: Typical Ejection Force Trace
Ejection force*
Initial or Static Breaking of die wall
ejection force adhesions
Compact moving
up the die
Dynamic
ejection force
Compact
emerging
from die
*[best presented as
ejection force per
unit area of die wall Time
contact]
16
Figure 13: Compaction Force versus Tablet Strength
16
14
Tensile Strength [MPa]
12
10
0
0 5 10 15 20 25
Force of Compaction [kN]
17
Work of Compaction Analysis of Force-Displacement Curves
30
25
20
Force [kN]
Lower punch
15
Upper punch
Wf
10
We
5
Wn
0
5 5.5 6 6.5 7 7.5 8
Punch Displacement [mm]
18
The Tableting Process
19
monitoring and control of the press maximum tablet diameters around 80 mm
operation. These additional features and capable of loads up to 200 kN or
become a necessity when it is no longer greater.
possible for an operator to react quickly
enough to ensure that the press is In a few cases, tablets can only be made on
operating in the validated mode, or the single-station type of machine, probably
to detect a problem early enough to because their way of operating gives the
avoid a major failure. material a longer dwell time under load,
and indeed, this is their main advantage.
Tablet Machine Design The output rate from single-station presses
can be increased by the use of multi-tip
Single-Station Presses tooling, but the rotary machine remains the
method of choice for large scale production.
The simple cycle of this type of press only Therefore, although a single-station press
offers the operator a limited opportunity may be used in the early stages of tablet
to make adjustments, as summarized in formulation development, it is imperative
Figure 15. that as soon as sufficient material is
available, the technology should then
It is, therefore, important that the press be transferred to a multi-station press
is not required to compensate for poor with dwell times as close to those in
formulations. Sizes of machines in this production as possible.
group vary widely from small ones, capable
of making tablets up to 12 mm in diameter, Multi-Station Presses
at rates of about 80 tablets per minute
(t.p.m.). These can exert maximum forces Multi-station presses involve the same
of the order of 20 kN. At the other end of three steps in the tableting cycle, but
the spectrum are large machines with these take place simultaneously in
different stations of the rotating turret
carrying the tooling (Figure 16 and Figure 17)
Figure 15: Operator Adjustments and generate a punch movement pattern as
Single-Station Press seen in Figure 18. However, the operator
only has a limited number of options in ad-
justing the running of the press (Figure 19).
Tablet thickness
[top punch penetration]
Press speed
[ejection]
[highest
position]
[fill volume]
[lowest
position]
20
The number of stations was commonly
around 16 in early machines, giving outputs
between 500 to 1000 t.p.m. with diameters
up to 15 mm, while high-speed contempo-
rary presses have closer to 80 stations and
outputs in excess of 12,000 t.p.m.
Upper punch
guide section
Filling Compaction Ejection
Die table
Lower punch
guide section
Weight Ejection
adjustment cam
cam
Feeder
Tablets exit
Ejection region
21
Figure 18: Rotary Press Punch Movements
Upper 8
[mm]
4
Level of top
of die cavity 0
-4
Lower
8 [mm]
-12
-16
0 6 12 18 24 30 36
Time [msec.]
22
Table 1: Differences Between Types of Presses
Single-Station Multi-Station
Filling
Exact weight Overfills, rejects excess
Compaction
Material at top of die cavity Material below top of die cavity
Punch Movement
Only upper punch moves Both punches move during
during compaction compaction
Dwell Time
100 to 300 msec. Can be less than 5 msec.
Ejection
Tablet brought just to surface Tablet brought clear of the die
of the die
23
at least continuously monitor the process (iv) Noise created by the higher speeds can
and the need for improved hygiene during increase to a level that is uncomfortable
operation to satisfy regulatory agencies. to the operator and even above that
permitted by regulatory authorities
High Production Rates (v) Capital costs for equipment may increase
beyond the reach of smaller manufactur-
Having briefly reviewed some of the more ers, or those with limited profit margins
basic aspects of tableting equipment, the
most popular innovative trends of this Other than following press operation
technology will now be discussed. One instructions, probably the six key factors
of the more important characteristics of involved in producing satisfactory tablets
a tablet machine is the rate at which the at high speed are:
machine can produce a product.
(i) Satisfactory robust and flowable
The ways in which individual manufacturers granulation
of equipment have sought to achieve higher (ii) Optimized press operating conditions
outputs fall into four groups: for that specific product
(iii) Variable speed feeders, optimally set-up
(i) By increasing the rate of compression, (iv) Satisfactory tail-over dies (seals the die
i.e., turret speed cavities between filling and compession
(ii) By increasing the number of stations steps) and lower punch flight controls
(iii) By increasing the number of points (prevents vertical movement of the dies)
of compression (v) Efficient dust extraction system
(iv) By increasing the effective number (vi) Electronic self-adjusting controls to
of punches, i.e., multi-tipped types monitor and control uniformity of
tablet weight and other key press
Each of these approaches has its own functions
particular advantages and disadvantages,
and in addition, all make demands on other High Turret Speed
aspects of press design and certain general
inherent characteristics of tableting have It is important to realize that in the fastest
had to be taken into account. running presses, horizontal punch velocities
may exceed 4 m/sec, and vertical punch
For example: velocities may exceed 2 m/sec. These
conditions require the most careful attention
(i) Formulations developed for slower to press design, construction and operation,
presses may not run satisfactorily on if acceptable levels of wear and trouble-free
higher speed machines production are to be achieved.
(ii) Some granulations may not flow fast
enough to fill the dies satisfactorily, so The press designer must always bear in
that weight variation from tablet to tablet mind the inherent relationship between the
increases centrifugal force, G, the pitch circle radius, r,
(iii) Need for a higher level of competency and the speed, n, (rpm) of the revolving
of the set-up personnel and machine turret, i.e.:
operators
24
G = k r n2 Many of the more recent models have two
identical compression stations, and have
where G is in multiples of the gravitational been shown to produce stronger tablets.
force and, in high-speed presses, may be In fact, in some cases, a higher first
as much as 10 times that of first generation compression force than the second can
multi-station machines. even be beneficial. It has been suggested
that one of the reasons for this observation
This leads to possible movement of is that higher first compressions result in
material in the die, which can be minimized higher temperatures of the material at the
by introducing a precompression stage, second point of applying load. The fill,
unless material is actually being lost from therefore, would be more ductile with
the die cavity. In this eventuality, it may be increased plastic deformation which may
necessary to take advantage of variable increase tablet strength, due to greater inter-
punch penetration to carry the particle bonding with fewer bond ruptures.
uncompressed material lower in the die,
or virtually seal off the cavities between Several press manufacturers now provide
filling and compression points with spring for operating their machines under these
loaded tail over dies. conditions. It is important to use large
diameter rolls at both stages, since small
A further problem associated with the rolls and high forces can lead to tableting
increased turret speeds is the chance problems due to a higher loading rate. A
of punch velocities along the camming, further refinement, which extends the time
particularly the weight adjustment cam, under load, is the addition of a spring-
exceeding some critical value leading to loaded section called a dwell bar between
a phenomenon known as punch flight. the first and second compression stages,
The machine modification of fitting which is said to facilitate even higher
springloaded plungers, which pressed production speeds.
against the punch body, originally developed
as anti-turning devices, is some help in this Cams
respect, but generated cams are now the
design of choice. For high-speed machines it has been
necesssary to ensure that punch heads
Precompression remain in contact with cam tracks by
installing so called generated cams, so
Most high-speed presses have a two-step as to avoid punch flutter. In these, the
compaction cycle, to facilitate removal of punches are forced to follow a specific
air from the feed, minimize loss of material path by being held firmly in a cam track
from the die cavity, and reduce the work of which controls all their vertical movements
the main compression rolls. This is achieved precisely.
by introducing a second set of smaller
compression rolls which can apply variable Many of the cams in newer presses are
but lower forces before the material reaches of special plastic construction to facilitate
the main rolls. high-speed operation, prolong cam and
tool life, and to produce less heat and noise.
It is also essential to keep the angle of the
25
weight adjustment cam track something surface. More sophisticated types are
less than 8°. This has involved the provision needed for high-speed machines which
of interchangeable cams which reduce the do not rely on gravity alone, but provide
excess of material originally filled into the a mechanism which assists material flow.
die. It should be noted that higher press
speeds may require more die overfill Contrary to some of the literature references,
because of greater density variations in the highest speed presses there are no
in the feeder. longer force feeders, but devices which
also partially fluidize the material and
The gradients on ejection cams also facilitate its transport into the die cavities
vary widely between vendors of presses, under the partial vacuum created by descent
and the debate continues as to whether of the lower punches. For this reason, it is
rapid or slow ejection is preferable. advantageous to control the rate of flow
Therefore, when switching products of material into the feeder chamber so that
between machines, this factor should there is space for expansion, i.e., it is not
not be ignored. choke fed. Also for this reason, many recent
designs incorporate three paddles (Figure
Feeders 20), by having an upper one which meters
material from the hopper to the twin paddles
The original method of feeding the dies was of the feeder. In earlier models, the speed of
from a stationary feed frame, material falling these paddle feeders was linked directly to
under the influence of gravity into the die turret speed, but it is now recognized that
cavities, the feed frame being designed to a variable speed, independent of the turret
pass material to and fro across the die speed, is preferable.
Die
26
It is important to appreciate that modern appropriate amount of a lubricant must be
feeders have a multi-functional role. In present at these surfaces at all times. It is
addition to feeding the dies, they also carry no longer possible to expect an operator to
on their leading edge, the device which achieve this requirement, and so presses
sweeps the ejected tablets from the press. are now fitted with ancillary equipment that
The trailing edge of the feeder incorporates provides individually measured amounts of
the blade which sweeps the ejected overfill lubricant on an optimized schedule, directly
material from the die cavities just before to all critical locations requiring lubrication.
they emerge from underneath the feeder. In many cases, transducers on the press are
constantly monitoring regions where failure
Adjustments of these two additional of the automated lubrication system would
controls, as well as an optimum clearance lead to increasing frictional forces, and they
between feeder and rotating die table, is can stop the press or activate some alarm
critical, and so the attachment and rigid system.
locking of the feeder onto the press is a vital
factor in successful operation. Even Increased Number of Stations
so, modern feeder designs provide rapid
release for removal and are easy to strip The best compromise between strength
down for thorough cleaning and inspection. of turret and maximum number of stations
which can be accommodated at a given
Lubrication diameter, involves three variables:
In the modern tablet press, the contacting (i) The diameter of the dies
surfaces of some individual components (ii) The distance between dies (known as
are under load and are moving relative to the web; see Figure 21)
one another at high speeds. It is obvious (iii) The size and geometry of the die locking
that to maintain successful operation, an mechanism
27
Turret Web for the above reasons, separate outlets are
to be preferred.
As more stations are fitted into the turret
so the metal web between the dies becomes This concept of multi-sequencing has now
thinner, retaining sufficient strength and been taken a stage further in a four-sided
providing adequate locking becomes a press in which the entire compression cycle
design problem. Die-locking nuts should is restricted to one quarter of the cycle and
only be tightened when the entire die set repeated to give a total of four tablets from
is fitted; torques not exceeding 15 foot- each station every revolution. This Magna
pounds should be used and a torque Press (Vector Corp.) has a rated output of
wrench employed. As little as 8 foot-pounds almost a million tablets per hour, achieved
may be adequate with new tooling. by using a large turret (90 stations), but a
low turret speed of 45 rpm.
Multi-Sequence Presses
Multi-Tipped Tooling
Reducing the entire sequence of the
compressional cycle into half the turret The ability to compress a particular product
periphery, as a means of virtually doubling on presses with different output rates,
output, was realized in the first double-rotary without affecting the time for the actual
presses just after the turn of the century. compaction cycle, is especially attractive,
By this means, two tablets are produced by for at least three reasons. The first is the
each station during each turret revolution. circumvention of difficulties associated
with some minimum compaction and
One of the more critical factors in operating recovery time, related to the deformation
these presses is to ensure that both sides characteristics of the major components.
of the machine are producing tablets Second is the need to allow a finite time
with closely similar characteristics. This for the displacement of the air inevitably
requirement is not as easy to achieve as present in the feed material, and finally,
might be expected, and some of the the flexibility offered by being able to run
differences encountered include: a single formulation on different machines.
(i) Feed to each side of the press is not In view of these factors, it is perhaps
the same, due to differences in level surprising that the use of multi-tip tooling
of material in the hoppers and/or has not been more popular. Typical multi-tip
segregation in them or the bulk container tools are shown in Figure 22 and up to six
(ii) The feeders are behaving differently tips per stem are now offered by some
(iii) Dust extraction not the same on both manufacturers. The most likely explanation
sides for any reticence to use this approach is
(iv) Punch penetration settings and/or overfill the increased restrictions on tablet diameter,
cams are different the need for keying of such tooling and
the higher initial and maintenance costs. For
In some machines, the tablets produced on the latter reason, the introduction of tooling
one side of the press are carried round to where the individual tips on a particular
the opposite side, so that there is a single punch stem are readily replaceable has
product outlet from the machine. However, immediate appeal, although matching and
28
maintaining constant overall length of each • Weight check device which samples
punch and tip demands an excellent tool press output
maintenance facility. • Tablet strength check on samples from
press output
A further disadvantage to this approach • Thickness and diameter check on
to increased output is the difficulty in samples from press output
instrumenting the press to measure the
compaction forces being generated at Multi-purpose control units, which
each punch tip. accomplish most of these functions and
others, are available from many vendors.
Ancillary Equipment
In addition, lights out operation may
The modern tableting process requires necessitate devices which monitor the level
several additional pieces of ancillary of the feed in the hopper and automatically
equipment to the press itself. The trend add more on demand. Similarly, a full
towards more automation and product container can be detected and
instrumentation, and in some cases to automatically substituted with an empty
introduce total automatic control of the one. These trends require provision of larger
process, the so-called lights out operating cubicles for each tablet machine, and it is
conditions, has increased the need for such important to consider this when planning
peripherals. new, or refurbished, tableting facilities.
Among the more common are: All the above peripherals are in addition to
the now commonly installed instrumentation
• Deduster attached to press outlet
• Metal check attached to deduster outlet
29
package available with virtually all high- can be reproduced exactly, only by the
speed presses. These packages facilitate possession of the template, thus
continuous automatic monitoring of machine counterfeiting is very difficult, yet any
performance, and can be coupled to the vendor can be asked to make the tooling.
various devices reviewed here.
Matched Tooling
Tablet Tooling
One of the most critical specifications
The punches and dies of modern tablet for tooling in contemporary multi-station
machines fall into the category of precision machines is uniformity of overall geometry,
tooling and, as such, should be treated with and, therefore, all tooling must be matched.
the proper respect. They are manufactured This is necessary because such machines
by special techniques to very close are now usually equipped with transducers
specifications, such as those defined to monitor the forces being exerted on the
in the IPT2 and Euronorm (Eurotooling) material in the die, and use this information
standards. A brief description of the steps to record and even control uniformity of
in this process will serve to emphasize the tablet weight. Applied force can only be
respect that should be given to tooling. correlated to tablet weight if tooling is
matched.
Punches
Inspection
Upper punches typically have more
clearance in the die than the lower ones, Full inspection of all punches and dies in
since only the former are required to move the set should be carried out before and
in and out of the die cavity. This greater immediately after use. If excessive or
clearance also serves to facilitate escape unusual wear is seen, the source must be
of entrained air. The barrels of shaped and identified and any problem rectified. Any
embossed upper punches are keyed to such occurrence is added to an on-going
prevent any rotation in the press guides. history of this particular set of tooling, and
Sculptured tooling, i.e., three-dimensional means that each set of tooling, whether off
profiles, can now be made (which are costly) or on the press in individual stations, must
or even different shapes within a single set, be identifiable. Some of the most critical
while retaining the same tablet volume. points to check for wear include:
30
manufacturing and advising on tablet tools. wishes, but pay very close attention to their
Probably, the best advice to give to a would- response. This is an area where taking
be purchaser of new tablet tooling is to sit expert advice can really be an extremely
down with the tool vendor, tell them your rewarding exercise.
Tablet Problems
31
Content Uniformity common measurement (crushing strength
is a misnomer). Resistance to surface
All the above factors contribute to content abrasion is also a popular test and is
uniformity, but in addition, this problem may expressed in terms of a friability value.
also be caused by non-uniform distribution
of active in the feed and/or segregation, Among the problems with the mechanical
and by preferential loss of active as fines integrity of tablets encountered during
during tableting. It is important to appreciate manufacture are capping, lamination,
that even the most sophisticated tablet chipping, stress cracking and sticking
machine may not be able to compensate (picking) of material to the punch faces,
for an essentially bad feed material, and it as illustrated in Figure 23.
is the responsibility of the formulators
to ensure that machines are fed with The strength of a tablet may be influenced
formulations of robust character. by the following parameters:
Capping Lamination
Picking
Chipping
Stress Cracking
Also poor friability
32
Capping and Lamination factors may contribute to this problem. In
addition, relaxation of various regions of the
Capping is the phenomenon where the tablet, as they emerge from the die during
upper part of the tablet horizontally ejection (Figure 24), may be a factor if
separates caps from the remainder bonding is weak and visco-elastic recovery
during ejection, or during subsequent is pronounced. The problem can sometimes
handling. Some of the factors that may be circumvented by the use of tapered dies,
contribute to this defect are listed in Table 2. i.e., the upper part of the die bore has an
The failure of tablets along several horizontal outward taper of 3° to 5°.
planes is called lamination and the same
33
Chipping inspection. It may be noted that the remedy
for stress cracking may involve significant
Sometimes tablets leaving the press, or changes to the formulation or process,
during subsequent handling and coating including the geometry of the tooling.
operations, are found to have small chips
missing from their edges. This fault is Picking
described as chipping and, in addition to
the obvious formulation deficiencies, may In some instances, a small amount of the
be caused by compaction conditions which tablet material may stick to the active punch
make too soft or too brittle tablets. Incorrect faces, and this is referred to as picking. As
machine settings, especially the ejection tablets are repeatedly made in this station
take-off plate and excessively harsh of tooling, the problem gets worse as
handling of bulk tablets after they leave more and more material gets added to
the press, may be additional factors. that already stuck to the punch face. The
Friability testing is a good indicator of an problem tends to be more prevalent on
inherent tendency for a given batch of upper punches. Among the remedies for
product to chip and should be a routine this phenomenon are those listed in Table 3.
in-process check.
One of the more useful procedures for
Stress Cracking determining the cause of this particular
problem involves recovering a small amount
Sometimes small, fine cracks can be of the material from the punches to which
observed on the upper and lower surface it is sticking. This material is then analyzed
of tablets, or more rarely on the side wall to find out whether it is rich in any compo-
(Figure 23). These are referred to as stress nent of the mixture, including the level of
cracks and in some cases it may be an moisture. This procedure is now perfectly
incipient problem which is not detected feasible with the sophisticated analytical
until attempts are made to coat the tablets, tools available today.
during packaging, or on final visual
34
Rate of Compaction (Press Speed) to values at least one order of magnitude
greater in machines often found in research
Due to the fact that some solid deformation and development facilities.
mechanisms are time-dependent, the
duration for which appreciable load is Switching from one press to another may
applied and the rate at which load is involve a change in:
applied may be highly significant. In other
words, sensitivity to strain-rate may be an • Compression roll diameter, which in turn
important property of materials subjected affects the loading profile on the material
to compaction. In terms of tableting, these • Change in turret size and, more
variables are often expressed in terms of specifically, the pitch circle, may also
the dwell time and rise time, respectively lead to a different loading pattern
(see Figure 9).
One example of a way to at least determine
Effects of Compaction Rate a rank order of loading rates is to calculate
a quantity called the constant strain period
The significance of this sensitivity to or CSP. This is the time during which the
compaction rate lies in the scale-up or punch head flat L (a fixed size in standard
transfer of formulations from slower research tooling) moves under the lowest point of the
and development tablet presses to the high- upper compression roll, or uppermost part of
speed machines commonly used in the pro- the lower roll, as illustrated in Figure 25. In
duction environment. In the latter case, dwell other words, the time during which the
times may be less than 5 msec. compared punch tips are closest to each other.
Head flat L
Pitch circle r
[cms]
Plan view
35
From a knowledge of only the pitch circle between slower/smaller presses and the
radius, r, and rotational speed of the turret, common high-speed presses found in
R (in rpm), the angular velocity, , and hence production. However, three key factors
the CSP can be calculated from the must be taken into account when scaling
following equations: up a tableting process.
36
Table 5 lists some common ranges of values specifications which must be maintained
of machine forces which are routinely through the various stages of development
monitored and will form the basis of to full-scale production.
• Ejection - 0 to 500 N
• Sweepoff - 0 to 10 N
• Pulldown - 0 to 100 N
• Pullup - 0 to 25 N
The cost of a new high-speed tablet press • Likely noise levels under normal
may exceed one million dollars and the operation
selection process is, therefore, a major • Capital cost of machine
exercise. The first decisions will be based
on what types of tablet production the There are many major decisions about
press is to be used for, including: the extent to which press-monitoring and
automation are required. In this context, it
• Desired range of tablet output must be remembered that, although very
• Maximum compaction forces sophisticated systems are now available,
• Types of tooling, i.e., tablet sizes and they do add substantial amounts to capital
shapes, keyed costs. The major items include the following:
• Need for two equal main compression
stations • Desired mode of operator-press
• Desirable type of feeder interaction
• Degree of automation anticipated • Method and degree of any weight control
• Monitoring and rejection of tablets which
Decisions concerning additional press are out of specification
characteristics usually follow logically, • Periodic sampling and testing of critical
including the following considerations: tablet parameters
• Recording of batch record information
• Ease of change-over of product • Storage of master product specifications
• Design and construction of critical cams
• Type and efficiency of dust extraction It can also be extremely valuable to conduct
system a thorough comparison of vendor profiles
• Details of the lubrication system before committing to a particular make of
37
press. Important factors (not in order of • Provision of comprehensive operator
importance) include: training
• History of company viability and stability
• Ease of access to a machine trial facility
• Reputation for meeting delivery Because added instrumentation may
agreements double the cost of the press alone, potential
• Local availability and extent of inventory purchasers should be encouraged to insist
of spare parts that vendors provide them with the level of
• Help with the development of the instrumentation they desire, by means of
validation package modular construction. This avoids being
• Service capabilities from local engineers forced to purchase unwanted features.
The last few years have seen a significant rather than purchased from a machine
increase in the number and variety of vendor.
instrumentation/automation packages
available from tablet machine manufacturers. Comtemporary Practice
Most are concerned with monitoring and,
to some extent, controlling production The common contemporary practice is to
presses, in particular, the minimization of purchase the necessary transducers and
tablet weight/hardness variation. Paralleling their associated electronics, together with
these have been some instrumentation a software package either from the tablet
systems designed more as an adjunct to machine vendor or a company specializing
the research and development function. in instrumentation. In some cases, special
Although, until recently, many of them have replacement parts, such as compression roll
been built by the researchers themselves, pins, punch holders and ejection cams, can
38
be purchased from the vendor as part of an More recently, sophisticated systems have
instrumentation package. been introduced (Compaction Simulators)
which are capable of mimicking (in real time)
It is common practice to take the analog the compaction cycle of any press and so
data from the above transducers, digitize have all the advantages of using a single
it, and transfer it either to a main frame station of tooling while still following rotary
computer, or more usually to a PC which press action, to a large extent.
is integral to most commercial packages.
Another recent important general
ITM’s in Research and Development development has been an increasing
interest in functionality testing and
The basic principles of the compaction evaluating tablet ingredients for consistent
process and their importance in the quality in terms of their role in the product.
technology of pharmaceutical tablets Among the important parameters which are
have already been reviewed. The need relevant to tableting materials are:
to establish the compaction behavior of
individual components and the total • Degree of Compressibility
tableting formulation, in order to optimize • Consolidation Potential
functionality, is a logical corollary. More • Compaction Rate Sensitivity
specifically, there is a need to quantify, • Lubrication Effectiveness
or at least rank-order, the intrinsic
compressibility and the consolidation Significance of Press Signals
potential of the materials. Sensitivity to the
rate of compaction and optimization of the Highly sophisticated instrumentation
lubrication level are two additional important packages capable of monitoring many
factors that should be studied. Measurement critical press functions are available on
of punch and die forces plus the relative most contemporary high-speed tablet
displacement of the punches can provide machines. In particular, the forces being
raw data, which when suitably processed exerted at each step of the press cycle,
and interpreted, facilitates evaluation of together with feeder torque and temperature
many of these compaction parameters. measurements, are proving invaluable in
detecting developing problems at an early
In spite of their historical use, it can be stage.
argued that the value of using a single-
station press for development work on Ejection Forces
formulations for preparing production
batches on multi-station presses is strictly It is now possible to purchase a press with a
limited. Where material factors, rather than special ejection cam capable of monitoring
process factors, are the most important, ejection forces from individual stations. If the
this is less true, unless the rate of loading is formulation has been adequately lubricated,
critical. Because of this latter factor, many these forces should remain small, i.e., a
workers have resorted to the use of fraction of 1 kN. Such instrumentation
instrumented, specially designed, small provides a powerful tool for ensuring
rotary presses as a preliminary step to optimum lubrication levels during formulation
transferring to a production type press. development, as well as a vital monitoring
39
function during production runs. out of the dies after tablet compaction, the
upper punch pullup force, UPPF, can also
If the ejection force monitor indicates be monitored. The most likely cause of
increasing values of these forces, then increasing pullup forces is penetration of
among the possibilities which may be fine material into the space between the
causing this are: barrel of the upper punch and the punch
guide. Another major cause is damaged
• Inadequate die-wall lubrication, usually tooling, but in such cases, the changes
seen at each and every station in pullup forces are usually much more
• Material between lower punch tip and variable from station to station.
the die-wall
• Material between lower punch barrel Sweep-Off Forces
and the punch guide
• Damaged tooling Possibly the smallest of the measured
forces at the present time is that necessary
Where the presence of material between to knock the tablet off the lower punch tip
the lower punch and the die wall and/or and out of the press (sweep-off). Values of
between the lower punch and its guide around 10 Newtons have been recorded.
is suspected, it indicates either wear on Unless the tablet size or shape is unusual,
these working surfaces or an excess of fine a significant increase beyond this level of
powder. As with the other likely reasons for force is indicative of tablet adhesion to the
this problem, the remedial steps are obvious. punch face and may even indicate filming
or picking. These necessitate immediate
Lower Punch Pulldown Forces and appropriate remedial action.
40
to sense such problems before they become can then be interpreted in terms of changes
serious and facilitates the trend towards in tablet weight. However, the translation
automation. of compressional force into an equivalent
tablet weight is not a simple process.
Commercial Instrumentation Packages Many factors have to be taken into
account, and there is a limit to the
The most recent developments in accuracy of the procedure.
instrumentation are the very sophisticated
micro-computer controlled systems, which Compressional force will only be a direct
in addition to all the features discussed function of tablet weight providing:
above, virtually take over setting up and
in-process monitoring from the operator. (i) The formulation is homogeneous, i.e.,
All the necessary information concerning of uniform density
each of the company’s tablets is stored (ii) The compressional force/tablet weight
in memory and is called up via a unique function is constant
product code. (iii) The volume of the die cavities at the
point of maximum compression is
Dialogue between the operator and the constant
computer-controlled press is via a terminal,
using menus. All machine settings and The latter supposition will only be absolutely
controls are effected by the microproces- valid when:
sors. Additionally, these computers usually
have provision for display and when • The overall length of the punches and
requested, a hard copy of the progress of tip geometry is constant
the batch being run. All in-process checks • The die bores are uniform
are done automatically at programmed • The pressure rolls are perfectly cylindrical
timings and any necessary adjustments and mounted centrally
made and logged. Finished tablets are
periodically removed from the immediate Although reaction due to tablet weight
press vicinity to a secure storage area. variation is usually greater, the resolution
All these aspects of the process, including of the instrumentation may well depend
every adjustment and important event, are on these factors.
noted by the computer and made available
as a hard copy manufacturing batch record
at the end of the process. It is very
important to involve the vendor in the
complex process-validation exercise
that must accompany commissioning
such a plant.
41
Special Tablet Types
Most of this section has been devoted to force to ensure that a good bond is obtained
conventional tablets, but there are some between it and the second layer. The same
more novel types such as layered tablets would apply to the latter if a third layer was
and those that are compression-coated. to be introduced.
In addition, there are those which are
not intended to be swallowed, such as The changes needed to modify the press
effervescent, chewable and lozenge forms, action to facilitate layering require removal of
although the latter may be prepared by one ejection cam from a double rotary
alternative techniques to tableting. The machine. It is usually not possible to run
properties, ingredients and processing of a press making layered tablets quite as
these special types of tablet may be quite fast as in the conventional mode. Other
different to those of the major group and manufacturing points include:
will be briefly referred to in this section.
• Better to use only simple tablet shapes
Layered Tablets • Must use a low first compression force
• Must ensure no cross-contamination
It is now possible to produce tablets of layers
composed of two or three distinct layers
of material of different composition. Compression-Coated Tablets
Some of the advantages associated with Tablet presses can also be modified to
this type of tablet are: compress a coating around a so-called
core tablet, also known as a tablet within
• Co-presentation of incompatible a tablet. In fact, it is possible to make a
medicaments tablet within a tablet, within a tablet!
• Facilitates repeat or prolonged action The advantages for this tablet form are:
properties
• Renders more difficult to copy or • Co-presentation of incompatible
counterfeit medicaments
• Gives a distinctive appearance • Facilitates repeat or prolonged action
properties
It is probably true to say that the latter • Permits coating without use of liquids
factor, if different colored layers are used, or heat
is just as frequent a reason to use the
method as any other. Perhaps the most important of these advan-
tages is the ability to coat without the use of
Among the main major manufacturing liquids. However, the finish on compression-
points that distinguish them from the coated products is not as good as that
types reviewed above is the need to pay obtained by conventional coating methods.
particular attention to dust extraction to
prevent cross contamination of the various Two general modified press types are
layers. Compression of the first layer must available. In one, the Manesty Drycoater,
be carried out at a fairly low compaction there are essentially two conventional
42
presses mounted on a single base plate monitor the final compaction force. In
and linked via a transfer mechanism. older machines a mechanical device in
the transfer arm was used.
Cores are manufactured on one press and
transferred to the dies of the second press, Effervescent Tablets
which already contain a proportion of the
coating material. The core is centralized Two distinct types of compressed tablets
and the remaining coating material added may be distinguished that possess an
just prior to the second compaction event. effervescent-base system: those intended
to be dissolved and the resultant liquid
The second type, the Kilian Prescoter, taken orally, versus those intended for
involves preparing the cores first on the external use only. The effervesence-
press or on a separate machine. The bulk producing medium is usually a mixture
cores are then fed by a special mechanism of organic acids and carbonates or
into the dies of the coating press, which bicarbonates, that release carbon dioxide
again contain a portion of the coating in the presence of moisture. Less frequently,
material. Similarly, the core should be as with systems intended only for external
soft as possible without failure during the use, peroxide mixtures are used to release
transfer process, and the second part of oxygen.
the coating material is added on top of
the centralized core. Undoubtedly, the major difficulty with
these special tablet forms is the need to
In both machines there are several important strictly control the humidity to which the
manufacturing constraints, including: ingredients are exposed. It is also important
to remember that the effervescent process,
• Better to use only simple tablet shapes once initiated, generates water which
• Must use a low core compression force serves to defeat the process of humidity
• Must ensure no cross contamination control.
of layers
• Specially modified press required Among the other unique requirements of
• Must ensure accurate positioning of these systems is the need to eliminate or
core tablet strictly minimize any water insoluble
• Usually operated at a slower speed component. In tableting, this presents a
than normal problem with respect to die wall lubrication.
Although there are several soluble lubricant
The two most critical of these are the possibilities, they all require higher concen-
centralization of the core in the coating trations than conventional ones such as
mass, and the need to ensure that each magnesium stearate.
coated tablet has one whole core inside it.
This latter requirement necessitates the use It is highly desirable that all processing
of a fail safe core detection system, with and packaging of effervescent systems
the capability to reject individual tablets not be carried out under carefully controlled
containing a whole core. The best method conditions, including:
with contemporary presses is to use the
sensitive force detection mechanisms to • Manufacture and storage in a controlled
43
temperature of 25° C From a manufacturing standpoint, many
• Manufacture and storage at a relative chewable tablets contain a high dose of
humidity below 25% RH drug and are consequently quite large. For
• Package in foil or plastic as soon as this reason, they are often compressed on
possible after manufacture machines using the larger D tooling and
capable of exerting higher compaction
Chewable Tablets forces.
Tablet Strength
The mechanical strength of compacts can compact to determine its strength, and
be interpreted in several ways including: there are many names given to the results;
e.g., hardness, crushing strength, fracture
• The force necessary to cause the resistance, tensile strength, etc. For this
structure to fail in some way reason, it is important to define the test
• The resistance to surface abrasion conditions precisely when reporting data.
• Surface hardness as measured by
resistance to indentation Breaking Force
44
The most correct name for this test is are capable of detecting the initial break in
breaking force. This parameter may be the tablet and recording the force that
defined as the compressional force, FC, caused it. Unlike earlier models, they
which, when applied across a specific plane do not continue to apply load that essentially
of the compact, just causes it to fracture demolishes the tablet structure and record
and is, therefore, a function of the compact that force.
geometry. The most popular version for
pharmaceutical tablets is to cause them to Tensile Strength
fail by applying a load across the tablet
diameter, or other fixed orientation, by When electronic-based testers are used,
means of a moving plunger, while the tablet the compact frequently has a clean break
rests against a fixed anvil, across its diameter, and it is then possible
as shown in Figure 26. to calculate a tensile strength ST from:
Fc
Instrument
must stop
instantly at
this point
This type of
failure needed
to measure
tensile strength
Fixed anvil
45
were manually operated. As a result, there References
were multiple sources of error, often caused
by aged instrumentation. In contemporary 1. Heckel RW, Trans AIME: 221, 671,1961.
models, plunger movement is motorized,
and the load on the compact is automatical- 2. Tableting Specification Manual, 3rd.
ly measured by means of an anvil or plunger Edition, APhA, Washington, DC, 1990.
electronically instrumented to measure the
load directly. Such instruments are prefer- 3. USP/NF, US Pharmacopeial Convention,
able for the reasons referred to above and Rockville, MD, 1995.
because of their superior accuracy.
Bibliography
Surface Abrasion
Solid Pharmaceutics: Mechanical Properties
The resistance of the surface of the compact and Rate Phenomena, J.T. Carstensen.
to attrition during subsequent processing Academic Press 1980.
(e.g., coating), handling and transport is of
general importance. There are several tests The Theory and Practice of Industrial
for assessing this property, but many involve Pharmacy, 3rd Edition, Lachman L.,
weighing the compacts before and after Lieberman H.A. and Kanig J.L., eds.,
subjecting them to a standardized period Lea & Febiger 1986.
of controlled agitation.
Principles of Powder Technology, Rhodes
For example, in the pharmaceutical industry M., ed., Wiley, 1990
a popular test is measurement of what is
termed friability. This involves subjecting Modern Pharmaceutics, Banker G.S. &
approximately 6 g. (wo) of dedusted tablets Rhodes C.T., eds.Dekker, 1990.
to a free fall of 6 inches for 100 times in
a rotating drum. The tablets are then Physical Characterization of Pharmaceutical
reweighed (w) and the friability, f, is Solids in Drugs and the Pharmaceutical
calculated from: Sciences, v. 70, Brittain H.G., ed. Dekker
1995.
f (in %) = 100 [ 1- (w/wo) ]
Pharmaceutical Powder Compaction
Values of f from 0.8 to 1.0 percent are Technology in Drugs and the Pharmaceutical
usually regarded as the upper limit of Sciences, v. 71, Alderborn G. & Nystrom C.,
acceptability. Similar procedures have eds., Dekker, 1995.
been used, but less frequently, to
determine the abrasion resistance of
pellets and even granular powders. 8/10/99-RS
46