Kuppuswamy R, Anderson SR, Augsburger LL and Hoag SW Estimation of Capping Incidence by Indentation Fracture Tests AAPS PharmSci 2001;
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article 5
(https://www.pharmsci.org/scientificjournals/pharmsci/journal/01_05.html).
Estimation of Capping Incidence by Indentation Fracture Tests
Submitted: September 7, 2000; Accepted: January 7, 2001; Published: January 18, 2001
R. Kuppuswamy1, S.R. Anderson2, L.L. Augsburger3 and S.W. Hoag3
1Pharmacia Corporation, Skokie, IL
2Dupont Pharmaceuticals, DE
3Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD
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Correspondence to:
L.L. Augsburger
Telephone: 410-706-7615
Facsimile: 410-706-0346
E-mail: laugsbur@rx.umaryland.edu
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Keywords:
Indentation Fracture
Capping
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Abstract
The purpose of this study was to predict the capping tendencies of
pharmaceutical powders by creating indentation fracture on compacts. Three sets
of binary mixtures containing different concentrations of each ingredient were
used in the study. The binary mixtures were chosen to represent plastic-plastic,
plastic-brittle, and brittle-brittle combination of materials. The mixtures were
tableted at different pressures and speeds on Prester®, a tablet press simulator.
These mixtures were also compacted on the Instron® Universal Testing Machine
4502. Static indentation tests were done on these compacts at different depths
until surface cracking and chipping were observed. The extent of surface
cracking and chipping was observed from light microscope and scanning electron
microscope images. A rank order correlation was observed between lamination
susceptibility and the depth at which indentation failure occurred. It was
concluded that indentation fracture tests could provide a useful estimate of
lamination properties of pharmaceutical powders.
Introduction
Lamination or capping of tablets as they emerge from the die or during
physical testing is one of the possible mechanical failures in tableting. The
problem can be alleviated in certain cases by altering the tableting conditions.
Reducing compression pressure and reducing decompression speed, within practical
limits, may help in overcoming capping or lamination; however, this is not a
universal solution. Increasing the binder or moisture content may be another
option. The dose may not allow the increase in binder content above a certain
level, and increasing the moisture content may cause stability problems. In most
cases, granulation of the drug substance may be the most viable option.
A few theories have been proposed to understand the causes for capping and
lamination. One such theory is that of air being trapped in the tablet under
pressure1,2 . After the upper punch starts receding, the entrapped air tries
to escape, thereby causing the tablet to cap. This theory is difficult to accept
as a universal explanation for capping or lamination because some formulations
cap or laminate even at low press speeds. At low speeds, there is sufficient
time for the air to escape during compression. In addition, micronized phenazone
compressed in a helium atmosphere has been shown to cap3 . Using helium
provides an atmosphere similar to air, with the difference being that the
smaller helium atoms escape after compression resulting in little entrapment
within the tablet. The inert nature of helium also ensures that there is no
adsorption on the solid particles. Mann et al4 suggested that the capping
pressure is related to the amount of air present in the granule bed prior to
compression. On removal of this entrapped air, capping was reduced but the
formulations still laminated. It was concluded that entrapped air may be
responsible for capping but it does not affect lamination. Other theories
attribute lamination and capping to the deformation characteristics of materials2, 5-8 . Train9 proposed that lamination was the result of radial elastic
recovery during ejection. The top of the compact recovers while the bottom is
still in the die, causing the top layer to laminate. The widely accepted theory
for lamination3, 10 attributes capping to the residual die-wall pressure,
which causes internal shear stresses in the tablet. The stresses cause
initiation and propagation of cracks, which result in lamination or capping. The
propagation of cracks could be prevented by plastic relaxation of shear
stresses. In other words, materials having sufficient plasticity may not be
susceptible to lamination.
The objective of this study was to provide a testing procedure or technique
that would predict the tendency of a powder or a mixture to laminate. The
technique used to predict lamination or capping of a material should be able to
measure its plasticity and relate it to its ability to prevent crack
propagation.
One of the techniques used to measure plasticity of materials or compacts is
indentation hardness measurement. Indentation hardness measurements have a wide
application in the pharmaceutical industry. Work hardening of materials has been
studied from indentation hardness measurements11 . Hardness measurement by the
impact method12 has been used to determine the physical integrity of tablets
by distinguishing between brittle and ductile failure13 . Tablet bonding has
been studied using hardness measurements14,15 . Indentation hardness measurement has been demonstrated to be a useful tool in predicting the shear
modulus of pharmaceutical materials16 ; however, it has not been an intention
in the pharmaceutical field to use the indentation test as a tool to create and
propagate cracks in a compact.
In a typical indentation hardness measurement done in our laboratory, the
indenter penetrates into the compact surface to a depth of 0.30 mm. What would
happen if the indenter were pushed further into the compact? How deep can the
indenter be pushed before the compact fails? When the compact does fail, is
there a specific pattern in which the compact surface breaks? Can any
information be obtained from such crack patterns? At what indentation depths do
these cracks originate?
The urge to investigate indentation hardness measurements beyond the normal
depths (0.30 mm) was the result of discontinuities seen in the displacement
versus time profiles of ibuprofen and naproxen17 . Visual inspection of
compacts after indentation revealed that the edges along the dent were not
smooth; cracks were seen on the surface of the compact. Generation and
propagation of cracks seem to be common features between indentation fracture
tests and lamination or capping during tableting; therefore, the hypothesis for
the present work is that indentation tests can be used to predict lamination or
capping tendencies of pharmaceutical materials.
Materials and Methods
Three families of binary mixtures were used in the study. The mixtures were
chosen to represent brittle-brittle, brittle-plastic, and plastic-plastic
combinations. Dicalcium phosphate dihydrate (DCP) (Encompress®) from Mendell
(Patterson, NY) and acetaminophen powder USP (APAP) from Mallinckrodt (Paris,
KY) were the model brittle materials used in this study. Microcrystalline
cellulose (MCC) (Avicel® PH 101) from FMC (Newark, DE) and magnesium stearate NF
(MS) from Mallinckrodt (Paris, KY) were the model plastic materials used in the
study. The mixture compositions are listed in Tables 1 through 3 . These
compositions were chosen because some of them capped at all tableting conditions
under which they were studied, some capped only at high pressure or speed, and
some did not cap at all. The powders were mixed in a 2-quart plexiglass
V-blender for 10 minutes (32 rpm, 300 g batch size). For mixtures with no
internal lubricant, a 2% wt/vol magnesium stearate suspension in acetone was
used to lubricate the die before tableting.
One portion of the mixtures was tableted on Prester® (East Hanover, NJ)18 (11 mm flat face
tooling, 350 mg, simulated Betapress® waveforms, 40 and 100 rpm, 150 and 300 MPa
peak compression pressure); 15-20 tablets were made at each tableting
condition.
The other portion of the mixtures was used for the indentation tests. Flat
cylindrical compacts were made on the Instron® Universal testing machine 4502
(IUTM)(Canton, MA). A schematic illustration of the IUTM
assembly is shown in Figure 1 . The die rests on a flat base and is held in
position by the die collar. A load cell of 10 kN capacity is mounted on the
IUTM. A flat punch, 11 mm in diameter, is attached to the load cell. The load
cell monitors the force during the compression cycle. The die used is vertically
split, which aids compact removal after compaction. The rate of compression and
decompression was 5 mm/min with a 10-second dwell time.
Compacts with minimum porosity were desired. Elastic recovery after
decompression increases the porosity of the compact. Also, there is a limitation
of 10 kN on the load the crosshead of the IUTM can support in the compression
mode. These factors, coupled with poor compressibility of certain mixtures used
in the study, resulted in a solid fraction of 78% to 79% being used in all the
studies. The compacts were not removed from the die before the indentation tests
were done; consequently, only axial relaxation of the compact was allowed. The
indentation tests were done in about 15 minutes (± 5) after the completion of the compression
cycle.
Indentation tests were carried out under a quasistatic condition. The IUTM
was used with a few modifications from the setting for compact formation. The
punch used in this case was the indenter, which has a diameter of 1.76 mm. A 500
N load cell was used for improved sensitivity. The minimum indentation depth was
0.30 mm and the maximum indentation depth was 0.90 mm or until there was
chipping on the tablet surface, whichever occurred first. The rate of
indentation was 0.05 mm/min. A 10-minute dwell time was employed at the maximum
indentation depth.
Scanning electron microscope (SEM) and light microscope (LM) images of the
compacts around the indentation were taken to observe surface cracks and
chipping, respectively. Compacts made of DCP-APAP mixtures could not be removed
from the die; therefore, the indentation depths at which surface cracks begin to
appear could not be recorded. However, the indentation depths at which the
surface began to chip off have been recorded.
Results
In this study, capping was categorized as a binary event; a mixture was
characterized to have a capping tendency when at least 1 of the tablets capped.
The tableting conditions under which capping was observed for the different
mixtures are shown in Tables 4 through 6 .
LM and SEM of compacts with the indentation are shown in Figures 2 through
14 . LM can detect tablet failure only when there is chipping of a surface layer.
On the other hand, SEMs can detect failure at an earlier stage, when cracks
begin to originate. As noted earlier, the DCP-APAP tablets could not be studied
under a microscope because they could not be removed from the die
successfully.
The minimum indentation depth for all tablets was 0.30 mm. For MCC-APAP
mixtures, compacts containing 25% wt/wt MCC chip at 0.30 mm indentation;
therefore, its SEM was not taken. For other mixtures, SEMs at various
indentation depths were taken. The SEMs shown include the depth at which cracks
originate and the more pronounced cracks at further depths. The depths at which
cracks begin to appear and the depths at which the tablet surface chips off are
recorded in Tables 7-9 . There is a rank order relation between the depth at
which cracks begin to originate and incidence of capping.
Discussion
There are 2 different theories proposed in the literature explaining the
origin of cracks and their propagation in brittle materials.
According to the "elastic failure model"19 , radial and lateral cracks and permanent impressions can be generated by elastic failure. Plastic deformation
is not necessary to explain the indentation damage of elastic, brittle
materials; however, for 2 reasons, this model may not truly represent the stress
states within the compacts studied here.
The strain rate of the indenter in the elastic failure model was as high as
231 m/s. This is an extremely dynamic event when compared to the strain rate
used in the static indentation hardness tests (5 mm/min). Whereas brittle
failure may be the primary or only mechanism of deformation at high strain
rates, plastic deformation is more likely at lower strain rates.
The elastic failure model was proposed for brittle materials like ceramics;
however, most pharmaceutical materials are plastic or viscoelastic. APAP is a
brittle material but its plasticity is more than that of ceramic or glass;
therefore, a model that explains indentation damage without plastic deformation
may not be appropriate for all pharmaceutical materials.
The "elastic-plastic model"20 explains the entire process in a manner that is more convincing for pharmaceutical materials. The assumptions and theories
underlying this model are described here briefly. During the indentation
process, it is not possible to visually examine the stress patterns as they
develop within the compact; therefore, the explanation given in this section is
the most likely one to describe the indentation event. The following explanation
for the origin and propagation of cracks is valid only where Poisson's ratio,
ν , is below 0.5. When
ν is above 0.5, the test
material is highly ductile. For highly ductile materials, tensile components of
the principal stresses disappear, thereby precluding the possibility of
initiating a brittle crack.
There exist compressive, shear, hydrostatic, and tensile stresses in the
compact undergoing indentation. The tensile component of the stress is
responsible for the initiation of a brittle crack. Once a crack is initiated, it
will tend to propagate in a direction perpendicular to the major tensile stress
components21 ; therefore, a crack developed beneath the indenter during
loading will progress further down axially. This direction is perpendicular to
the tensile stresses, which act radially. The progression of cracks sideways is
restricted by the compressive components of the principal stresses. The
propagation of the lateral cracks during decompression relieves die wall
stresses.
Initial loading produces a zone of irreversible plastic deformation about the
contact point. At some critical indenter load, a crack suddenly initiates below
the contact point. This is called a median vent. It is possible that several
median vents could originate at the same time. Increasing the load further by
pushing the indenter deeper into the compact causes stable extension of the
median vent. The median vents close but they do not heal completely when the
indenter unloads. Just before the unloading phase, the compact is under residual
tensile stresses, in addition to the compressive stress. This causes cracks to
develop sideways and lateral vents to appear. As the indenter unloads, lateral
vents continue to extend. The rate of growth of lateral vents depends on the
rate of unloading. If the material does not have sufficient plasticity, the
lateral vents grow fast enough to reach the tablet surface. This causes chipping
on the tablet surface.
The indentation depths at which median vents begin to appear depend on the
strength of the material. It is a flaw in the compact induced by deformation by
the indenter that causes the development of the median vents. The extents to
which the lateral vents develop and spread are a function of the deformation
nature of the material. Plastic materials have the ability to curb the growth of
lateral cracks; therefore, materials with higher strength and plasticity have a
better chance of preventing the initiation and propagation of cracks. This
criterion is the same as that required for prevention of capping or lamination;
therefore it is not surprising to see a correlation between the failure of a
compact in an indentation test and susceptibility of the same material to cap or
laminate in a tablet press.
The critical concentrations of APAP in DCP+APAP and MCC+APAP mixtures at
which capping begins to occur may correspond to the percolation threshold of
APAP. As explained by the percolation theory22 , at low concentrations of
APAP, capping may occur as finite clusters in the infinite clusters of DCP and
MCC, respectively. The critical concentration of APAP at which capping is
observed in each of these 2 systems of binary mixtures may be the point where
APAP may begin to percolate throughout the system. However, percolation theory
may not be able to explain the critical capping concentration MS in MCC+MS
mixtures. There is no evidence in the literature wherein a material could cross
the percolation threshold at a concentration as low as 3%. MS has a low shear
strength and is a laminar lubricant; therefore, it may be able to spread
throughout the system and interfere with MCC-MCC bonding.
Conclusion
Static indentation tests that create cracks on the tablet surface at 0.50 mm
indentation depth or lower indicate susceptibility of the material to laminate.
If there are no cracks up to 0.70 mm indentation depth, there is little risk of
capping. If cracks begin to develop between 0.50 and 0.70 mm indentation depth,
the material has to be treated with caution. The material may cap under extreme
tableting conditions, which may be at either high pressure or high speed.
The susceptibility or tendency of a new material or mixture to cap can be
predicted from the SEMs and LM after the indentation tests. This study could be
extended beyond binary mixtures with the inclusion of formulations that have
been known to cap or laminate. The crack patterns of these formulations after
indentation tests could serve as standards for capping and laminating
materials.
When a new chemical entity is to be evaluated, indentation tests could be
carried out on the materials at different indentation depths (depending upon the
quantity of material available). A visual observation of the surface cracks and
their comparison with established standards may provide a useful estimate of the
capping or lamination propensity of the new chemical entity.
Acknowledgements
The authors wish to thank the following: Rajen Shah, PhD, for his technical
expertise; Paul Grosenstein and Greg Argentieri of Novartis Pharmaceuticals for
the micrographs; Metropolitan Computing Corporation for use of Prester®; and
Novartis Pharmaceuticals for providing the funding and laboratory facilities for
the research.
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