T2205

Tablets Strength Measurement by Next-Generation Tablet Strength Tester (NGTST)

Frank Cheng and Mike Markham, Adare Pharmaceuticals
Adare Pharmaceuticals, Princeton Pike Corporate Center, 1200 Lenox Drive, Lawrenceville, NJ 08648

RESULTS:
Some Adare ODT tablets with different APIs having different dosage strengths, tablet
dimensions and various excipients were tested by the device. The relationship between tablet
dosage strengths, excipient contents, tablet dimensions, and manufacturing processes, etc.
with the tablet crushing strengths were checked. The tablet hardness of the same samples was
also measured by using conventional tablet hardness tester. By comparing the data between
the crushing energies and hardness, it was demonstrated that while the two sets of data have
some correlation, the data generated by the new device are with a higher degree of
consistency then those obtained by the hardness tester. The results demonstrated that the
new device can be used to distinguish fracture properties of tablets even when they are
compressed to the same hardness.

A sample holder was constructed of two clear acrylic resin plates, 50X50 mm, with center
hole of 20 mm in diameter on each plate. Two steel rods, 60 mm long with 2.54 mm
diameter, are held in between the plates by four screws. The sample holder can be used
to hold the test tablets in either diametral or three-point bending testing position.

Figure 2. Photo Picture of the

Next Generation Tablet Strength
Tester (NGTST)

Objective
To assure its quality commitment and in compliance of quality by design (QbD) principle,
Adare had previously developed a method and device to measure the pharmaceutical
tablet strength (fracture energy) which can better quantify the tablet intrinsic strength
than the currently available USP tablet hardness tester.1 The objective of this research is
to further enhance the previous design in hope that the concept and design of the
instrument can be used to replace or to supplement the current USP tablet breaking
force method <1217> in order to manufacture the best possible ODT tablets.

3-point bending

12
10

Several Adare ODT tablets were used to compare the tablet strength data generated
by NGTST and a conventional hardness tester under different sample orientations.
Table 3 lists the data comparison between fracture energies (mJ) and hardness (N)
when the samples were placed in diametral and three-point bending impact positions.

8
6
4
y = 0.0363x - 4.5243
R2 = 0.96002

2
0

100

200

400

300

500

600

Method
An Up-and-Down method2 was used to establish the drop height required to break
a tablet. A preselected mass is dropped from different heights and the heights which
cause the tablets to break are recorded. This is repeated until 6 reversals (change of
failure/no failure, usually by using 20 fresh samples) are obtained.

Where:

E is the impact fracture energy, in erg (g-cm2/sec2, or 10-4 milli-Joule, mJ)

m is the mass of the impactor, in grams
g is the gravitational law constant, 980.7 cm/sec2
H is the drop distance in cm

Results

10.2

9.58

ADA101 250 mg

6.74

7.13

ADA103 25 mg

11.2

12

ADA104 100 mg

12.4

13.1

Figure 10. Fracture Energy Comparison between Old and Next

Generation Tester

250

Average tablet weight (mg/Tablet)

1410

1060

705

Tablet Thickness (mm)

6.20

5.50

4.94

Tablet Diameter (mm)

17.4

15.4

13.2

Axial

16.07

13.99

9.58

3-point bending

14.15

8.01

5.08

Fracture Energy (mJ)*

*Data from 20 tablets using NGTST

47.1

ADA101 250 mg

4.38

14.14

9.58

33.7

ADA103 25 mg

6.52

22.6

11.9

27.7

A second ODT tablet, ADA 102, with four different dosage strengths were tested for
their fracture energy (mJ) along with the tablet breaking force (N), obtained by a
Dr. Schleuniger Model 6D Tablet Hardness Tester. Table 2 lists the results and Figure 7
compares the data. The data indicates a good correlation (R2>0.95) between dosage
strength and tablet fracture strength (mJ) obtained by NGTST, while the tablet
hardness data (N) did not show a significant correlation (R2=0.75).

ADA104-A 100 mg

9.64

26.7

13.1

47.3

ADA104-B 100 mg

10.32

30.8

9.91

38.3

ADA 102 200mg

7.33

26.7

6.91

36.6

ADA 102 100 mg

6.25

20.3

5.18

27.8

ADA 102 50mg

3.26

17.2

6.26

24.3

ADA 102 Dosage Strength (mg)

200

100

50

25

Average tablet weight (mg)

810

405

203

101

Tablet thickness (mm)

5.36

4.33

3.02

2.44

Tablet Diameter (mm)

14.2

11.2

9.25

7.11

Axial fracture energy (mJ)*

9.28

5.73

5.15

4.61

Diametral fracture energy (mJ)*

5.56

3.63

2.86

2.10

Tablet breaking force (N)**

35.4

23.7

27.5

20.8

35

Figure 7. Correlation between ADA 102 Dosage Strength and Tablet

Fracture Energy

y = 0.071x + 20.191
R2 = 0.75508
Axial fracture energy (mJ)*
Diametral fracture energy (mJ)*
Tablet breaking force (N)**

35
30

30

50

15

30
20

10

0
0

25

40

10

6
NGTST (mJ)

10

12

y = 2.2362x + 14.762
R2 = 0.57179

10

15

NGTST (mJ)

y = 0.0191x + 1.743
R2 = 0.99378

0
0

50

100

150

Dosage (mg)

10

12

14

Conclusions
A new generation tablet strength tester (NGTST) was developed by Adare
Pharmaceuticals. The portable device offers many advantages over the old version
by incorporating some new parts, such as: a clear Delrin tubing which can be seen
through to better focus on the impact point; a small steel ball impactor, which can
improve the dropping distance measurements for better accuracy and resolution; an
external magnetic handle to raise the impactor to minimize the frictional energy loss.

Through forward thinking, Adare Pharmaceuticals, a leader in patient-centric

products, successfully developed a device which can be used to design and test ODT
tablets, in compliance with FDAs QbD initiative in pharmaceutical product life cycle
management.

References
1. F. Cheng and M. Markham, A Novel Impact Tester for Measuring the Strength of
Pharmaceutical Tablets, poster #R6313, presented at AAPS Annual Convention, 2014.

y = 0.0267x + 3.6904
R2 = 0.9596

10

20

20
15

The experimental data obtained at Adare Pharmaceuticals indicate that NGTST,

similar to its previous version device, offers a better method to test tablet
robustness than the USP tablet hardness method. The device measures the fracture
energy instead of the breaking force and the information is useful in tablet
anisotropy determination, which is important for products not made of elastically
isotropic, homogenous materials.

60

20

NGTST also incorporated the use of a sample holder which offers three measurement
positions, e.g. axial, diametral and three-point bending. The data generated by
these positions can be compared directly to those obtained by the conventional
tablet hardness devices.

70

25

NGTST (mJ)

Diametral Data comparison

y = 2.0924x + 8.3427
R2 = 0.88161

Figure 9. Diametral Data

Comparison

Three-Point Bending Data comparison

10

The correlation results obtained by the three-point bending position are plotted in
Figure 8 and those from the diametral position are displayed in Figure 9. The data
indicate that the three-point bending results correlated better (R2=0.88) than those of
the diametral ones (R2=0.57). This result indicates that the three-point bending data
generated by NGTST can be better used to predict those from the tablet hardness data.

Figure 8. Three-Point Bending

Data Comparison

y = 1.0603x + 0.2937
R2 = 0.94348

Table 2. ADA 102 ODT Tablets Fracture Energies and Hardness

As shown in Table 1 the tablet dosages are proportional to tablet weights. This implies
that the tablets are made from the same homogenous granulates.

Hardness (N)

16.07

40

375

NGTST (mJ)

30.14

Table 1. ADA101 Tablet Strength

500

Hardness (N)

10.53

ADA 102 Tablet Strength

Dosage (mg/tablet)

12

NGTST (mJ)

ADA101 500 mg

*Obtained by testing 20 tablets.

**Average of 10 tablets.

Table 1 lists the physical description and the tablet strength results obtained by NGTST
and the correlation data are plotted in Figure 6.

14

Diametral

As shown in Figure 6 the axial and three-point bending strength of the tablets are
proportional to their dosage strength, with R2>0.9. This indicates the two
measurements can be used to determine whether the granulate materials are
homogenous in nature.

An Adare Pharmaceuticals ODT tablet, ADA 101, with three dosage strengths were
tested for their tablet strength by using this new device.

Figure 5 shows a three-point bending experiment. The test sample is placed on top of
two steel rods. The rods are separated at a premeasured distance, L, about 8 mm
apart. The striker is then placed at the center of the sample, with equal distance (L/2)
from the two supporting rods, to receive fracture energy from the impactor.

ADA101 500 mg

ODT Tablets

Table 3. Comparison of Tablet Strength Data Generated by NGTST and

Hardness tester
Three-point Bending

The results obtained were compared with the tablet breaking force results obtained
from a conventional tablet hardness tester, Dr. Schleuniger Tester, Model 6D. Results
are also compared with those obtained by the Adares older model.1

Figure 4 shows the diametral impact experiment. In this experiment, the tablet is
placed vertically in the middle of the two steel rods of the sample holder. A flat
surface striker is placed on top of the sample and the tablet is subjected to the striking
force similar to that of tablet hardness testing.

Fracture Energy by Next

Generation Tester (mJ)

Fracture Energy Comparison

Dosage Strength (mg)

Several ODT tablets from Adare Pharmaceuticals, either marketed products or the
experimental formulations, were used to check tablet fracture energies.

Figure 3 shows the arrangement of the impactor, striker and test sample when the
tablet is tested on axial (horizontal) impact position. In this test, the up plate of
sample holder is removed and only the lower one is used to direct the sample.

Fracture Energy by
Older Tester (mJ)

The impact energy (E) is calculated by using the gravity law equation:
E=m*g*H

Figure 1. Design of the Next

Generation Tablet Strength
Tester (NGTST)

Axial

14

The flat end of the striker is used for a diametral (radial) strike on the radial edge of
a sample tablet in a way similar to the conventional tablet hardness test. The pointed
end of the striker is used for axial and three-point bending experiments, to deliver the
striking energy to a specific point of the test sample.
In a typical experiment, a tablet is placed in the middle of the sample holder and the
striker is placed at the desired point of the test sample. The steel ball impactor is then
raised to a height by using the magnet arm. After recording the height, the magnetic
arm is swung away from the tube to release the impactor, which delivers the striking
energy to the test sample. The tablet is then evaluated for breakage and the amount
of energy delivered is calculated.

A significant advantage of NGTST over the previous version is the use of the sample
holder. This accessary can provide a direct comparison between the fracture energy
data and the hardness data generated by the conventional tablet hardness tester,
under the same testing positions.

16

Figure 2 shows the fabricated device. A clear Delrin tube of i.d. is used as the main
body to host the impactor. A steel ball, weighing 7.116g, is used as the impactor (any
magnetic ball of any weight of similar size can be used). A striker made of Teflon rod,
with either a flat end or a pointed end, is used to deliver the striking force to the test
samples.

CONCLUSION:
The new device offers many advantages over the tablet hardness tester and other similar
testers. The advantages of the new generation device over the previous device engineered
by Adare includes: use a light weight steel ball as the impactor, which minimizes the fraction
energy loss and increase the dropping distance for more accurate height measurements, use
of a rare earth magnet attached to a handle to raise and release the dropping ball, and the
use of external handle eliminating additional weight attached to the dropping mass which can
cause uneven fall of the dropping mass. The use of a much improved tablet holder affords
direct comparison of data obtained by this new device with those obtained by the conventional
tablet hardness tester. It has demonstrated that the results obtained by this new device are
robust and can be used in choosing excipients of appropriate isotropicity and homogeneity in
making desirable ODT tablets. The device can therefore offer a new tool to test and design
better patient-centric products in compliance with applying QbD approaches in developing
pharmaceutical products.

18

y = 0.026x + 3.4783
R2 = 0.95881

Table 4. Axial Fracture Energy comparison Between Old and NGTST Tester

Old Tester (mJ)

A next-generation tablet strength tester (NGTST) was designed and fabricated by Adare
Pharmaceuticals. The device consists a clear Delrin tube, in diameter and 18 in length,
which is supported vertically by a ring stand. A steel ball falls freely through the tube to
deliver the gravitational energy to a striker, placed directly at a desired impact point on the
tablet. The striker transfers the crush energy to the tested sample and the energy is measured
by the weight of steel ball, multiplied by its drop height and gravity constant, according to
the gravity law equation, E=m*g*h. A high-strength neodymium permanent magnet attached
to a horizontal handle is used to raise the ball. The handle can be moved up or down along
the vertical column of ring stand to bring the ball to a desired height and then the ball is
released by swinging the magnet away from the tube. The handle therefore serves as an
indicator for height measurement. An Up-and-Down procedure is used to establish the drop
height required to break the tablets. A tablet holder was also constructed. The accessory can
hold the tablets in either vertical, horizontal or a three-point bending position to receive the
impact energy.

APAP Tablet Strength

Hardness (N)

METHODS:

Figure 6. Tablet dosage (mg) vs. Tablet Fracture Energy (mJ)

Hardness (N)

Adare Pharmaceuticals is a global leader in oral drug delivery technologies, including products
of taste masking formulations; orally disintegrating tablets (ODT); bioavailability enhancement
tablets (BET); and other patient-centric drug products. One of the most challenging issues in
developing the ODT tablets is to determine the tablets strength, as tablets need certain
strength to survive the manufacturing processes and patients handling, while weak enough
to be disintegrated rapidly in the oral cavity. The compendia testing method, USP <1217>
Tablet Breaking Force Test, is considered inadequate as it measures the maximum force to
break a tablet but not its true strength, i.e., the brittle, ductile and work of failure. The
purpose of this work is to develop a new generation tablet strength tester, similar to ASTM
Drop Weight Tester (e.g. ASTM E208), which can accurately measure the energy instead of
force required to break a tablet. The information can be used to correlate the tablet strength
to other anisotropic properties of a tablet, such as the API contents and the excipients used.
The data are important in formulating a desirable ODT tablet with the intended use, robust
enough to survive manufacturing, packaging, and end user handling yet weak enough to
maintain adequate oral disintegration properties.

The basic design of the device is shown in Figure 1. The device consists of a lightweight impactor and a striker to deliver the impact force to the tested samples
(tablets). The light-weight impactor affords a long drop distance for a better
resolution in measuring the tablet strength. The use of an indirect impact design
ensures the accuracy of the impact. This is accomplished by placing a striker at a
desired tablet location. The impactor is dropped onto the striker which in turn
transfers the energy to break the tablet.

Figure 5. Sample
Holder for ThreePoint Bending

Fracture Energy (mJ)

PURPOSE:

Material

Figure 4. Sample Holder

for Diametral Impact

Tablet Strength

Abstract

Figure 3. Sample
Holder for Axial
Impact

The data (Tables 1 and 2) indicate that the tablet fracture energies (mJ) are
proportional to the tablet dose (mg). Since the tablets were made from the same
granulate mixtures and the tablet weights are proportional to the tablet dose, this
implies that the granulates are made of homogenous material. Therefore, the fracture
energy may be a good indication that the granulation materials are isotropic in
nature, even though the materials are different.3,4

200

250

To compare the fracture energy data generated by NGTST and the previous version
device, several ODT tablets were tested for their axial fracture energies. The data
obtained are compared in Table 4 and plotted in Figure 10. The results indicate the
two data sets correlated well (R2=0.94). This verifies the consistency of the instruments.

2. K.A. Brownlee, J.L. Hodgest, Jr., and M. Rosenblatt, The Up-and-Down Method with Small
Samples, American Statistical Association Journal, vol. 48., 1953, pp.262-277.
3. K. E. Wilson and A. Potter, Advantages of Impact Testing Over Hardness Testing in Determining
Physical Integrity of Tablets, Drug Devel. Ind. Pharm. 24(11), pp 1017-1024 (1998).
4. M.P. Mullarney and B.C. Hancock, Mechanical property anisotropy of pharmaceutical
excipient compacts, Int. J. Pharm., vol. 314 (1), pp. 9-14. (2006).