American Journal of Medical Sciences and Medicine, 2014, Vol. 2, No.

4, 71-76
Available online at http://pubs.sciepub.com/ajmsm/2/4/2
© Science and Education Publishing
DOI:10.12691/ajmsm-2-4-2

Technological Excipients of Tablets: Study of Flow

Properties and Compaction Behavior
J. Conceição*, M. Estanqueiro, M. H. Amaral, J. P. Silva, J.M. Sousa Lobo

Research Centre for Pharmaceutical Sciences, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of
Pharmacy, University of Porto, Porto, Portugal
*Corresponding author: [email protected]

Received September 04, 2014; Revised September 09, 2014; Accepted September 11, 2014
Abstract The physical properties of pharmaceutical powders/granules are very important in the development of
oral solid dosage forms. The aim of this paper was, in a first stage, to carry out an evaluation of the flow properties
(angle of repose, flow time, compaction capacity, compressibility index, Carr index and Hausner ratio) of
technological or primary excipients of tablets (microcrystalline cellulose and dibasic calcium phosphate dihydrate)
which behave differently during compaction, either pure and in binary mixtures, whose composition varied between
20% (w/w) and 80% (w/w) at intervals of 20% (w/w). In a second stage, using an instrumented eccentric tableting
machine, energies and exerted forces during compaction of these materials were measured and the compressibility
curves were registered. In addition, plasticity index and lubrication coefficient were calculated and weight
uniformity, thickness, hardness and tensile strength of the manufactured tablets were also evaluated. The obtained
results demonstrated that the binary mixtures and the pure excipients showed similar flow properties. On the other
hand, the obtained tablets with the plastic excipient had lower values of exerted force by the upper punch and
apparent net energy, and higher values of plasticity index and time periods of the force/time compression profiles.
Keywords: excipients, binary mixtures, flowability, compaction, tablet instrumentation
Cite This Article: J. Conceição, M. Estanqueiro, M. H. Amaral, J. P. Silva, and J.M. Sousa Lobo,
“Technological Excipients of Tablets: Study of Flow Properties and Compaction Behavior.” American Journal of
Medical Sciences and Medicine, vol. 2, no. 4 (2014): 71-76. doi: 10.12691/ajmsm-2-4-2.

(< 25-30°), flow time (< 10 s/100 g), compaction capacity

1. Introduction (CC) (<20 ml), compressibility index (CI) (< 15%), Carr
index (CrI) (< 15%) and Hausner ratio (HR) (< 1.25).
Drug delivery systems are physical systems whose Officially the compression process was first started in
properties depend, among others, on the individual 1843 by William Brockedon and since then, few changes
contributions of active pharmaceutical ingredient(s) and were made [11]. Nevertheless, the knowledge of the
excipients. Some advantages like high-precision dosing, process of tableting changed radically in the early 1950s,
manufacturing efficiency, and patient compliance make when Higuchi introduced the instrumented compression
tablets the most popular dosage forms [1]. Direct machines that allowed to measure the forces that
compression is the preferred method for the preparation of intervened in the process [12,13]. The use of instrumented
tablets but this process is extremely dependent on the tablet machines is essential for basic research in
powders characteristics and it is estimated that less than compression physics, as it facilitates product development,
20% of pharmaceutical materials can be compressed optimization and scale up, and enables monitoring and
directly into tablets [2,3]. control of production [14].
The propensity of powders to flow under given The production of tablets is a complex process
circumstances (flow ability) affects a large number of involving many variables and a number of engineering
industrial applications [4]. In pharmaceutical industry, the principles [1]. According to Marshall, the set of
knowledge of the compressibility characteristics of phenomena that occur during the preparation of tablets is
powders/granules is crucial in the development of oral called compaction and is divided in two phases, namely,
solid dosage forms. However, these tests are usually compression (reduction in bulk volume and particle
performed with pure excipients and there are only a few rearrangement) and consolidation (increase in the
published studies concerning mixtures of excipients. mechanical strength and particle-particle interactions
Pharmaceutical powders are described as formation) [15].
heterogeneous systems characterized by their particle size, Commonly, the applied force in materials compression
morphology, density, specific area, roughness, porosity exceeds the elastic limit, and fracture or plastic
and interparticle forces [5]. The flow properties used in deformation is the main compression mechanisms [16,17].
order to predict the compression ability of a powder and their Particles deformation can be reversible (elastic
criteria of analysis are the following [6-10]: angle of repose deformation) or irreversible (plastic deformation).
72 American Journal of Medical Sciences and Medicine

Force, time and displacement curves have usually been d500

studied to acquire information on the compaction HR = (5)
d10
properties of pharmaceutical materials [18,19,20].
Mathematical equations, such as those of Heckel (1961), where d is the apparent density, m is the weight of the
Cooper and Eaton (1962) and Kawakita and Lüdde sample, V is the apparent volume, V0 is the apparent
(1970/1971), have been generated to describe force volume before tapping, V10is the apparent volume after 10
profiles [18,21,22,23]. taps, V500is the apparent volume after 500 taps, d0 is the
The major objectives of this article were: (i) to evaluate apparent density before tapping, d10 is the apparent
the flow properties (angle of repose, flow time, CC, CI, density after 10 taps, and d500 is the apparent density after
CrI and HR) of technological excipients used in tablets 500 taps.
manufacturing which behave differently during The angle of repose (mean ± SD, n = 3) and flow time
compaction, either pure and in binary mixtures; (ii) to (mean ± SD, n = 3) were evaluated with a granulate flow
measure energies and exerted forces during compaction of tester (Erweka GT, Germany) according to the European
these materials using an instrumented alternative machine Pharmacopoeia 8 [8]. The funnel used can have different
DOTT Bonapace (model CPR-6) coupled to a computer; diameter apertures and the tested diameter was 10 ± 0.01
(iii) to calculate the plasticity index (PI), according to mm (nozzle 1) [8].
Stamm and Mathis, and the lubrication coefficient (R); (iv)
to register the force/time, force/displacement, work/time, 2.4. Compaction Procedures
work/displacement and the position of the upper
punch/time compression profiles; (v) to determine the Pure excipients and the binary mixtures were directly
periods (consolidation time, dwell time and contact time) compressed and the study of the physicalparameters of
of the force/time compression curves; (vi) to characterize compression (mean ± SD, n = 10) was performed using an
the manufactured uncoated tablets (evaluation of weight instrumented alternative machine (DOTT Bonapace,
uniformity, thickness, hardness and tensile strength). model CPR-6, Italy) coupled to a computer. The volume
of the compression chamber was kept constant for all
samples. At the same time, the upper punch displacement
2. Materials and Methods was adjusted in order to obtain tablets with adequate
hardness and this position was maintained during the
2.1. Materials experiments. The punches had 11 mm diameter with
plane surface and all assays were done at room
The tested materials were microcrystalline cellulose temperature and 60-70% relative humidity.
(Avicel® PH-200 (AV), FMC Corporation, United States) With software Cosalt-write, Cosalt-read and FIMA
and dibasic calcium phosphate dihydrate (Emcompress® Compression Data Analysis, it was possible to measure
(EMC), JRS Pharma, Germany). the energies (total energy supplied by the upper punch
(ES); expansion energy (EEXP), i.e., the energy lost by
2.2. Preparation of Powder Mixtures instantaneous elastic recovery; and apparent net energy
Four binary mixtures of AV with EMC were prepared, (ELA), i.e., the energy effectively expended in obtaining
whose composition varied between 20% (w/w) and 80% tablet) and forces during compaction (exerted force by the
(w/w) at intervals of 20% (w/w). The mass of each upper punch (FS) and applied force in the lower punch
powder mixture was 150 g and the mixture was (FI)) and to register compression curves (force/time,
performed in a Turbula WAB mixer (T2F, Switzerland) force/displacement, work/time, work/displacement and
for 15 minutes. No lubricant was used. the position of the upper punch/time). The time periods of
the force/time cycle of compression were evaluated
according to the following definitions [24,25]: dwell time
2.3. Flow Properties Measurements is the time between the points corresponding to 90%
For each mixture and pure excipient, the apparent maximum force; contact time with the compression force
volumes (mean ± standard deviation (SD), n = 3) were is the time between the points corresponding at 10%
evaluated using a Tap Density Tester (Electrolab ETD- maximum force; and consolidation time corresponds to
1020, India) according to the European Pharmacopoeia 8 the necessary time to reach maximum force.
[8]. Afterwards, the values of apparent volume were used The PI, according to Stamm and Mathis, and the R
to calculate apparent density, CC, CI, CrI and HR by the were also evaluated using the following equations [26,27]:
following equations(mean ± SD, n = 3) [6-10]:
ELA ( ES − EEXP )
d ( g / ml ) =
m (1) PI ( % ) = × 100 = × 100 (6)
V ES ES

CC ( ml=) V10 − V500 (2) FI

R= (7)
( V0 − V500 ) FS
CI ( % )
= × 100 (3)
V0
2.5. Characterization of the Tablets
( d500 − d 0 ) Weight uniformity (mean ± SD, n = 10, analytical
Cr I ( % )
= × 100 (4) balance Mettler AE 200, Mettler Toledo, Switzerland),
d500 thickness immediately after ejection, after 1 hour and 15
 American Journal of Medical Sciences and Medicine 73

days later (mean ± SD, n = 10, electronic digital 3. Results

micrometer, Mitutoyo, Japan) and hardness (mean ± SD,
n = 10, Erweka TBH 28, Erweka GmbH, Germany) were In this work, two technological excipients of tablets
evaluated in the obtained tablets. commonly used in pharmaceutical industry, and their
Tensile strength (mean ± SD, n = 10) was assessed binary mixtures, that behave differently during
using equation 8, as it takes into account the dimensions compaction were studied, i.e., AV is an insoluble diluent
of the tablets [28]. with plastic behavior and EMC is an insoluble diluent
2P with fragment able behavior. They are direct compression
Tensile strength = (8) excipients and an important tool in formulation and
π Dt
design of tablets [19,29,30,31].
where P is the hardness (N), D and t are the diameter (mm)
and thickness (mm) of the tablet, respectively.

Table 1. Results of flow properties (mean ± SD, n =3), compaction behavior (mean ± SD, n = 10), weight uniformity, hardness, thickness and
tensile strength of tablets (mean ± SD, n = 10)
Parameter AV Mixture 80:20 Mixture 60:40 Mixture 40:60 Mixture 20:80 EMC
CC (ml) 16 ± 1 14 ± 2 12 ± 0 11 ± 2 9±0 8±2
Cr I (%) 16.7 ± 0.4 15.5 ± 0.8 15.2 ± 0.9 14.7 ± 0.9 14.7 ± 0.4 16.2 ± 2.7
CI (%) 16.7 ± 0.4 15.5 ± 0.9 15.1 ± 0.8 14.7 ± 0.9 14.7 ± 0.4 16.2 ± 2.7
HR 1.08 ± 0.01 1.07 ± 0.01 1.07 ± 0 1.07 ± 0.02 1.08 ± 0 1.08 ± 0.02
Flow time (s/100 g) 20.3 ± 0.1 20.1 ± 0.2 16.0 ± 0 13.3 ± 0.1 10.4 ± 0 10.1 ± 0
Angle of repose (degrees) 39.3 ± 1.2 39.7 ± 0.8 40.7 ± 0.6 39.6 ± 0.9 39.9 ± 0.6 44.4 ± 0.2
FS (N) 2501 ± 32 3391 ± 18 4594 ± 161 7289 ± 622 19795 ± 1114 -
FI (N) 2060 ± 44 2879 ± 17 3731 ± 117 5778 ± 460 14475 ± 804 -
R 0.82 ± 0.01 0.85 ± 0.0 0.81 ± 0.01 0.79 ± 0.01 0.73 ± 0.0 -
ES (J) 3.41 ± 0.05 4.19 ± 0.02 5.21 ± 0.17 6.96 ± 0.44 14.25 ± 0.79 -
EEXP (J) 0.08 ± 0.01 0.10 ± 0.02 0.15 ± 0.01 0.24 ± 0.03 1.20 ± 0.16 -
ELA (J) 3.33 ± 0.04 4.09 ± 0.02 5.06 ± 0.15 6.72 ± 0.43 13.05 ± 0.64 -
PI (%) 97.7 ± 0.3 97.6 ± 0.4 97.1 ± 0.1 96.6 ± 0.4 91.6 ± 0.7 -
Consolidation time (ms) 116.4 ± 0.4 116.2 ± 0.4 114.5 ± 0.5 109.3 ± 0.8 98.9 ± 1.9 -
Dwell time (ms) 39.1 ± 0.2 36.2 ± 0.2 34.1 ± 0.1 31.6 ± 0.3 29.4 ± 0.9 -
Contact time (ms) 177.9 ± 0.3 174.5 ± 0.4 169.7 ± 0.5 161.8 ± 0.8 152.5 ± 1.7 -
Weight (mg) 322 ± 2 371 ± 1 426 ± 4 505 ± 11 645 ± 9 -
Hardness (N) 75 ± 2 88 ± 2 93 ± 3 88 ± 5 84 ± 9 -
Tensile strength (N/mm2) 1.13 ± 0.03 1.37 ± 0.03 1.46 ± 0.06 1.38 ± 0.08 1.29 ± 0.14 -
0 minutes 3.833 ± 0.004 3.718 ± 0.005 3.686 ± 0.004 3.680 ± 0.005 3.774 ± 0.016 -
Thickness (mm) 1 hour 3.854 ± 0.003 3.729 ± 0.006 3.699 ± 0.003 3.687 ± 0.004 3.777 ± 0.015 -
15 days 3.890 ± 0.004 3.754 ± 0.009 3.746 ± 0.004 3.724 ± 0.005 3.792 ± 0.017 -

Figure 1. Force (kN)/time (s) compression profile obtained from one Figure 2. Force (kN)/displacement (mm) compression profile obtained
tablet of mixture 80:20 from one tablet of mixture 80:20
74 American Journal of Medical Sciences and Medicine

with EMC keeping constant the volume of the

compression chamber and the upper punch displacement
(conditions maintained constant during the experiments).

Figure 3. Work (J)/time (s) compression profile obtained from one tablet
from mixture 80:20

Figure 6. Compression profile obtained from one tablet of mixture 80:20

Figure 4. Work (J)/displacement (mm) compression profile obtained

from one tablet from mixture 80:20

Figure 7. Position of the upper punch(mm)/time (s) compression profile

obtained from one tablet of mixture 80:20

4. Discussion
Many researchers have attempted to study the
compaction behavior and compressibility of binary
mixtures of some pharmaceutical excipients during
compression [19,32-36]. For instance, Busignies et al. [34]
observed that the specific compaction energy was
proportional to the mixture composition expressed in mass,
but this was not the case for the specific expansion energy.
It can be seen from Table 1 that pure excipients and
their binary mixtures presented similar CI and CrI
Figure 5. Compression profile obtained from one tablet of mixture 80:20
(<16.7%), CC (<20 ml), HR (<1.25) and angle of repose
The obtained results of the flow properties (mean ± SD, (39.3-44.4°) values. However, the flow time value
n =3), compaction behavior (mean ± SD, n =10), weight determined with EMC was about half of the value
uniformity, hardness, thickness immediately after ejection, obtained with AV. Increasing the amount of EMC
after 1 hour and 15 days later, and tensile strength of decreased the flow time. Values of CI and CrI below 15%
tablets (mean ± SD, n =10) are shown in Table 1. Figure 1, indicate good flow properties but values above 25% mean
Figure 2, Figure 3, Figure 4, Figure 5, Figure 6 and Figure poor flow [15], and values of HR of about 1.00–1.25
7 exhibit an example of recorded compression profile. indicate free-flowing powder, 1.26–1.45 indicate poor
Uncoated tablets with acceptable physical properties flow, and >1.46 an extremely poor flow [8]. A value of
were produced. But it was not possible to prepare tablets angle of repose less than 30° usually indicates free
 American Journal of Medical Sciences and Medicine 75

flowing material, up to 40° indicates reasonable flow List of Abbreviations

potential, and above 50° means that the powder flows with
great difficulty [9]. AV - Avicel® PH-200
From the values of the FS, it was possible to CC - Compaction capacity
differentiate the tested materials. In this way, as the CI - Compressibility index
amount of EMC and the average weight of the tablets CrI - Carr index
increased, the value of FS also increased. Besides, as FS EEXP - Expansion energy
increased, the ELA also increased. ELA - Apparent net energy
All the analyzed materials presented a value of R < 0.9. EMC - Emcompress®
In a correctly lubricated pharmaceutical powder/granule, ES- Total energy supplied by the upper punch
the R value is greater than 0.9 [27]. Values of R lower FI - Applied force in the lower punch
than 0.8 indicate an inadequate lubrication, as verified for FS-Exerted force by the upper punch
mixtures 40:60 and 20:80, as expected due to the lack of HR - Hausner ratio
lubricant [27]. PI - Plasticity index
All the obtained compaction curves showed the same R- Lubricationcoefficient
configuration and Figures 1, 2,3, 4, 5, 6 and 7 illustrate an
example. As far as the periods measured in the force/time
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