The document discusses the significance of tensile strength over tablet hardness in comparing various tablet formulations, emphasizing that tensile strength is a more valid metric for tablet quality. It details how factors like tablet size, shape, and compression pressure significantly impact tablet properties, thereby complicating direct hardness comparisons. The text further elaborates on the process of normalizing data to facilitate accurate comparisons across different tablet characteristics and formulations.

1. Delivery and Formulation
Tablets Under Pressure
By Michael Gamlen
The hardness of a tablet has traditionally been used as a measure of
and Dipankar Dey at quality; however, tensile strength is more appropriate when comparing
Gamlen Tableting Ltd
tablets of different composition, shape and size, and compressed on
different pieces of equipment.
The modern tablet is a complex – preventing a priori prediction unable to measure compression
drug delivery system in which of quality. force. It is a very important control
the drug substance is combined parameter because compression
with a number of excipients to aid This causes manufacturers affects every tablet property,
formulation of the desired product; particular problems in developing including disintegration, dissolution
these include bulking agents, and producing the ideal tablet and friability. In some cases stability
binders, disintegrants and coatings, that fulfils its therapeutic purpose, is also affected. However, tablet
all of which have some function and can be manufactured both hardness (or breaking force)
to aid processing of the drug efficiently and economically. comparisons are applicable to
substance into the end-product. The Even small variations in material one tablet size and shape only. If
excipients and drug substance are properties or process parameters the size, shape or thickness of a
processed through a number of unit can have profound effects on final tablet is materially changed, then
operations such as mixing, blending, tablet quality. all tablet hardness comparisons
granulation, tableting and often will become incorrect. It is obvious
coating to form the final product. Measuring the Correct that it is more difficult for a small
Tablet Properties tablet to withstand a given fracture
The final tablet has to fulfil a load than a larger tablet. Simple
number of characteristics, including To assess the impact of hardness measurements are thus
the ability to deliver the correct starting material properties and not a valid basis for comparison in
amount of drug substance into the manufacturing conditions on this situation.
patient’s system at the required tablet properties, it is important
rate, as well as physicochemical to ensure that the correct In fact, there are two factors at work
properties that make it easy to characteristics are used when here. One is the area across which a
handle, administer and store. For making comparisons between tablet breaking force is applied, as
dispensable products, these include tablets comprising different clearly the strength of the tablet will
a suitable size, hardness, texture and formulations or made on different be proportional to the area across
stability, as well as taste and smell. pieces of equipment. In fact, it which the force is distributed.
Innovations in Pharmaceutical Technology issue 42. © Samedan Ltd. 2012
is actually very difficult to make
Process and formulation scientifically robust comparisons The second factor is that, if the
development of the desired tablet between formulations and same compaction force is applied
form is time- processes for a number of reasons. to (say) a 6mm circular tablet and
Keywords consuming and a 3mm circular tablet, the force
complex because Tablet hardness, or breaking per unit area on the small tablet
knowledge of strength, is an important and will be four times that on the large
Tableting excipient/drug widely used parameter to control tablet (because area is proportional
Tablet hardness substance material the tablet manufacturing process. to the square of the diameter of a
Compression force properties and In many cases, it is used as a circle). So the material in the 3mm
Compaction pressure their relationship surrogate measure for compression tablet will experience a compaction
to processing force during manufacture – often pressure four times that of the 6mm
Tensile fracture stress
parameters is limited because the tablet machine is tablet at the same load.

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Figure 1:
Hardness of 3mm and 6mm diameter Avicel PH-102 tablets thickness of the tablet and
200
Comparison of compression force must also
a 3mm and 180 6mm tablets be taken into account so that a
6mm tablet
160 3mm tablets graph of TFS versus compaction
140 pressure can be prepared.
Tablet hardness (N)
120 The differences in tablet thickness,
diameter and compression
100
force for circular tablets can
80
then easily be accounted
60
for by calculating the tablet
40 tensile fracture strength
20 and tablet compaction
0 pressure.
0 1 2 3 4
Compression force (kN) Tablet Tensile Fracture Stress
For cylindrical tablets, TFS can be
It is essential that these factors (measured by breaking force); calculated from the breaking force
are taken into account when making however, this takes no account of according to the following equation,
comparisons between tablets. the differences in tablet thickness, first used by Fell and Newton in
or the effect of differences in 1970 (1):
Instead of comparing breaking compaction pressure (see Figure 2).
loads (measured in Newtons or Only the applied compression force 2P
kg), tablets should be compared is quoted, which does not take σt = —
using breaking stress (‘pressure’), into account the punch diameter, Dt
which in engineering terms is and hence the area over which the
called the tensile fracture stress compaction force is applied. where σt is the tensile fracture
(TFS) (1). Rather than comparing strength of the tablet, P is the
compaction force, we should Making Valid Comparisons fracture force (N), D is the tablet
compare fracture stress based on diameter and t is the overall
the work of Newton et al (2). When Comparing formulations using thickness. The equation takes
we do this, the results make much only compression force and account of the breaking load,
more sense. hardness does not reveal all of the thickness and diameter of the
information available in the data. tablet, and effectively divides the
In Figure 1, 3mm and 6mm tablets To make the proper comparison, breaking load by the area of the
appear to have a similar hardness the tablet punch diameter, fracture surface.
Figure 2: Thickness and diameter need to be
accounted for in any tablet hardness quote
6mm
3mm
Thickness
Thickness

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Figure 3: The Tensile fracture stress for 3mm and 6mm diameter Avicel PH-102 tablets For tablets that are not flat-faced,
tablet tensile 14 the cross-sectional area of the die
strength
6mm tablets is still normally used.
comparison for 12
a 3mm and 3mm tablets
Tensile fracture stress (MPa)
6mm tablet
10 TFS/Compaction Pressure
Comparisons
8
6 When TFS and compaction pressure
are reviewed, the data reveals
4 its full value. By using the tensile
strength for tablets and normalising
2
the applied force with the punch
0 diameter to give the compaction
0 100 200 300 400 500 600 pressure, we can see the impact of
Compaction pressure (MPa) tablet size and compaction pressure
on TFS, and the effect of tablet size
appropriate formula must be used to on compressibility.
calculate the TFS for the comparison
to be valid. The effect of increasing compaction
pressure on tablet tensile strength
Compaction Pressure is shown in Figure 3. There is an
For a flat-faced tablet, compaction area of overlap of around 150MPa
pressure is calculated simply by of compaction pressure where
dividing the force applied by the the tensile strength of a 6mm
die area: tablet is similar to that of a 3mm
tablet. Normalising the data in this
P way provides an objective way to
Figure 4: The Gamlen This formula is only correct for Cp = — measure tablet physical properties
Tablet Press GTP-1 flat-faced cylindrical tablets; for A over a wide range of compaction
Images: Gamlen convex-faced round tablets, the pressures and using a small amount
Tableting Limited
formula becomes: where Cp is the compaction of material. The data shows that the
pressure and A is the area of the die. behaviour of Avicel PH-102, when
compressed into a 30mg tablet
10P
σt = As mentioned earlier, at the same of 3mm diameter, is completely
t t W compression force, punch diameter scalable to the behaviour of a
(2.84 — – 0.126 — + 3.15 — + 0.01) has an exponential effect on 100mg tablet of 6mm diameter.
D W D compaction pressure. For example, Similar results have been obtained
400kg of compression force on a for other materials (2).
where σt is the tensile strength, P 3mm punch produces four times the
is the fracture load, D is the tablet pressure as 400kg on a 6mm punch.
diameter, t is the overall thickness
and W is the wall height of
the tablet.
Both of these
equations are also
listed in monograph
1217 of the United
States Pharmacopeia.
Similarly, an equation
for a wide range of
elongated tablets has
been derived by Pitt et
al (3). Hence if tablets
of different shape are
to be compared, the

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Figure 5: Compaction (top), ejection purpose as it is both a tablet press
(middle) and fracture (bottom) profiles and a tablet fracture tester. For the
for an Avicel PH-102 tablet
measurement of tablet breaking
load, the press records both force
TFS Measurement and displacement during both
in Formulation compression and fracture, and also
Development provides the ejection force profile
associated with tablet ejection
Tensile fracture stress (see Figure 5).
measurement is an
important material property In the scale-up of tablet
independent of tablet size. production, the press can be used
Any statement requiring a to determine the relationship
specific hardness to pass between tablets developed at
a friability test or survive the bench-top scale using a few
a coating operation is not grams of material (often at the
universally applicable as it early development stage) and the
would apply to one specific final tablet manufactured on a
size only. Normalising the rotary tablet press. The latter uses
data would remove that hundreds of kilograms of material,
barrier and help in comparing making process development
formulations of different difficult because of practical
tablet sizes and shapes, or difficulties in experimentation;
compressed on different smaller and different shaped
equipment. tablets can, however, be scaled
to the final desired tablet
Comparison of tablet TFS is design if TFS is used as the
relatively straightforward basis for comparison.
if tablets are made at a
controlled compaction Conclusion
pressure. At Gamlen, we
have developed a bench-top, While tablet development
computer-controlled tablet has traditionally used tablet
press (the GTP-1, Figure 4) hardness as a measure of the
that is well-suited for this physical attribute of a tablet,
tensile strength is in fact more
appropriate when comparing
Michael Gamlen is Managing Director of Gamlen Tableting Limited (Nottingham,
UK), a leading provider of expertise, equipment and services in the design, different formulations and tablets
development and manufacturing of pharmaceutical tablet dosage forms. compressed on different pieces of
Awarded a first class honours degree in pharmacy, specialising in pharmaceutical equipment and at different scales.
engineering, he studied for a PhD at Nottingham University (UK). He was Head of
Tablet Development at the The Wellcome Foundation for 15 years, and has since References
worked for Vanguard Medica Limited and as a consultant. Michael has over 30 years’ experience 1. Fell JT and Newton JM,
of tablet development and specialises in managing product development, formulation, tablet Determination of tablet
and process development studies. He has been teaching professional tableting courses for strength by the diametral
many years and his courses are highly rated, often exceeding the expectation of participants.
compression test, J Pharm Sci
Email: michael@gamlen.co.uk
59, pp688-691, 1970
2. Newton JM, Rowley G, Fell JT,
Dipankar Dey is an Oxford-educated doctoral graduate with extensive senior
et al, J Pharm Pharmacol 23
management experience in the pharmaceutical and medical diagnostics industries.
Dipankar joined Gamlen Tableting Ltd from Oystar Manesty (Liverpool, UK) where Suppl 195S-201S, 1971
he was Head of Process Development. He has particular expertise in manufacturing 3. Pitt KG and Heasley MG,
solid dose and biopharmaceuticals, and has worked in a number of different Determination of the tensile
functions including technology transfer, new product development, training and strength of elongated tablets,
manufacturing. He also has experience in film coating and the implementation of Process Analytical Powder Technol, in press,
Technology (PAT). Email: dip@gamlen.co.uk http://dx.doi.org/10.1016/j.
powtec.2011.12.060