EVALUATION OF BRIDGING LIQUID FOR SPHERICAL

AGGLOMERATION OF BENZOIC ACID

MSc Jyothi Thati and PhD Åke C Rasmuson*
Department of Chemical Engineering and Technology
Royal Institute of Technology (KTH)
SE-100 44 Stockholm, Sweden
rasmuson@ket.kth.se

Spherical agglomerates of benzoic acid have been successfully prepared by drowning-out

crystallization in water-ethanol mixtures. A third solvent is used as a bridging liquid, and in this
work the influence of the bridging liquid on the agglomeration and on the mechanical properties
of the product particles, are explored. The product particle characterization includes the particle
size distribution, morphology and mechanical strength. It is found that, not all solvents having a
very low solubility in water can be used as bridging liquid. It is also found that the properties of
the spherical agglomerates formed depend on the choice of the bridging liquid. The compression
characteristics of single spherical agglomerates reveal properties that may be favorable for
tabletting by direct compression.

1. Introduction

Particles of less than 10µm in diameter are often needed in, e.g., pharmaceutical or fertilizer
industries, because of their high biodispersibility or dissolution kinetics. But handling and
processing of these particles is very difficult and time consuming. In this context, the spherical
crystallization process, by which spherical agglomerates can be produced, may be attractive
because it can lead to significant improvements in the handling properties of materials.

Spherical crystallization can combine several processes into one step, including synthesis,
crystallization, separation and agglomeration. It is performed in a three (good, poor solvent and
bridging liquid) partially miscible solvent system. Spherical crystallization is a solvent exchange
crystallization method in which crystal agglomeration is induced through the addition of a third
solvent, termed the "bridging liquid", which preferentially wets the solid surface. These wetted
particles will collide and the bridging liquid hold the particles together by forming liquid bridges
between them and further collisions cause large spherical agglomerates to form (Farnand et al.,
1961). This behavior is similar to liquid bridge formation in granulation, except the continuous
medium is liquid instead of a gas.

In previous work (Katta and Rasmuson 2008), needle-like benzoic acid crystals were
transformed into spherical agglomerates with improved mechanical properties. The influence of
the overall process design and the operating conditions were studied. In this paper the effect of
bridging liquid on spherical agglomeration of benzoic acid is explored.
2. Experimental work

Solvents used in this work are chosen based on the principle of spherical crystallization. As for
simple spherical agglomeration the first solvent (ethanol, 99.7% purity purchased from Solveco
chemicals AB) should have a good solubility of benzoic acid, the 2nd solvent (water) is the anti
solvent that crystallizes the benzoic acid from the feed solution and the 3rd solvent is to be
immiscible with the 2nd solvent. This liquid is supposed to collect the small crystals and hold
them together by forming liquid bridges between them. Different solvents are considered as
bridging liquids based on the immiscibility with water. Those included are carbon tetrachloride,
chloroform, cyclohexane, 1,2-dichloroethane, dimethyl formamide, dichloromethane, ethyl
acetate, hexane, methyl-tert-butyl ether, toluene, methylene chloride and 2,2,4-
trimethylpentane. Among these, solvents that are reasonably environmentally friendly are
selected for spherical agglomeration experiments. In the present study bridging liquids used are
cyclohexane (99.5%, VWR), ethyl acetate (99.8%, VWR), toluene (99-99.4%). In our previous
work chloroform was used as a bridging liquid (Katta and Rasmuson 2008).

In the experiments, benzoic acid is dissolved in ethanol at 400C to a concentration (0.375gm/ml)

corresponding to saturation at 200C. After dissolution, this solution can be kept at room
temperature for a sufficient time without crystallizing. To 15 ml of this solution at 200C, is added
the desired amount of bridging liquid. Then the mixture is fed by a syringe pump, at the
selected feeding rate, onto the surface of 85ml of water agitated in a 250ml jacketed crystallizer
(6 cm in diameter). The agitation is provided by a three-blade marine propeller (2.5 cm in
diameter) centrally located with the blades 1 cm from the bottom. The agitation rate is 600rpm.
The temperature is controlled by a heat and refrigerated circulation unit (Julabo, FP50-HP).
After 1 hour the experiment is terminated and the agglomerates are filtered, washed with water
and dried at room temperature.

The amount of bridging liquid used is reported as volume of bridging liquid/ volume of solid
used (BSR). The volume of solid is determined as the weight of solid originally dissolved divided
by the density (ρ) of benzoic acid (1316kg/m3, Kirk – Othmer 1992).

The dry spherical agglomerates are sieved with woven wire test sieves of DIN 4188 standard, in
10 min intervals until the weight of the different fractions remain constant. The particle size
distribution is obtained by weighing the sieve fractions. The morphology of the agglomerates
from each sieve fraction is recorded by optical microscopy (Olympus SZX12). The agglomerate
strength is determined by compressing agglomerates in a material-testing machine (Zwick
2.5/TS1S) using a 10N load cell. The diameter of each particle (d) is determined at the time the
extensometer is touching the particle. 30 agglomerates are randomly selected from each sieve
fraction of each batch to find the average fracture force and fracture stress. Fracture force is
defined as the force (first peak in Fig 1) required for the first breakage. The measured fracture
force (F) is recalculated into fracture stress (σ) by Equation1
F
σ= (1)
⎛ πd 2 ⎞
⎜⎜ ⎟⎟
⎝ 4 ⎠
 1

0.8
Force (N)

0.6

0.4

0.2

0
0 200 400 600 800 1000

Displacement (µm)

Figure 1: Force vs Displacement curve of sieve fraction 1000-1250µm: bridging liquid =toluene
Benzoic acid conc. =0.375 g/ml, N= 600rpm, BSR =0.93, Feeding rate= 1.7ml/min.

For a few agglomerates the same particle is exposed to repeated compression – release cycles
(0.5mm/min) to evaluate the elasticity of the particles. For single particle compression the
maximum force used is 0.5N, which corresponds to a maximum stress of 0.43 MPa based on the
particle cross sectional area. As a complement, also the compression characteristics of a bed of
particles have been evaluated. About 100 to 150 mg of agglomerates are poured into a
cylindrical steel cup (8.2mm in diameter) and the bed is compressed up to 10N (0.19 MPa).

The elastic recovery for each compression is calculated by Equation 2.

⎡ He − Hc ⎤
Elastic Recovery = ⎢ ⎥ (2)
⎣ Hi − Hc ⎦

Initial size (Hi) and the minimum size (Hc) of the agglomerate at maximum compression is
determined, as well as the size of the particle after releasing the load (He).

The compressibility of the powder bed is also characterized by a compressibility index where ρ p
is the bed bulk density at maximum compression and ρ 0 is the bed bulk density of the original
powder bed. If the volume of the bed is

V = Volume of cylinder = 4 π r 2 H

M
and the bed bulk density (ρ) =
V
the compressibility index can be calculated from:

ρ p − ρ0 H i − H c
Compressibility Index = = (3)
ρp Hi

3. Results and Discussion

Since successful spherical agglomeration relies on that the adequate amount of bridging liquid is
added, introductory experiments were perform to identify an optimum BSR for each bridging
liquid. With ethyl acetate it was not possible to produce spherical agglomerates of benzoic acid
at the conditions of the present work. It may be noted that ethyl acetate is slightly more soluble
in water compared to other bridging liquids used.

Particle size distribution

The cumulative mass size distribution of the product particles using different bridging liquids is
shown in Fig 2. Obviously, the selection of the bridging liquid can be used to influence on the
product particle size. In the present work, the largest spherical agglomerates are produced by
using toluene. The mass mean size becomes about 1400 µm. The smallest agglomerates are
produced by using cyclohexane, with a mean size of about 700 µm. There is a slight difference
in the amount of bridging liquid used, but we believe that most of the influence comes from the
chemical difference of these two bridging liquids. Differences in wettability of benzoic acid
crystals (Amaro and Biscans 2002) and in solubility in water may contribute to explain the
differences.
Cumulative under size

1
0.8
0.6 Chloroform
0.4 Toluene
Cyclo hexane
0.2
0
00
00 00
0
45 0
63 3 0

0 0

50 50
00 00

0
00 00
00
25
45

80 -80

12 -12
14 -14
16 -16

20
10 -10
6

-2
0-
0-
0-
0
25

Sieve size (µm)

Figure 2: Influence of bridging liquid on product particle size distribution at 200C: Benzoic acid
conc. = 0.375 g/ml, N= 600rpm, feeding rate=1.7ml/min, BSR = (cyclohexane 1.06, chloroform
and toluene 0.93).
In Table 1 is presented the yield defined as the amount of solid product formed divided by the
total amount of benzoic acid originally dissolved in the ethanol.

Table 1: Influence of bridging liquid on the yield at 200C: Benzoic acid conc. = 0.375 g/ml, N=
600rpm, feeding rate=1.7ml/min.
Bridging liquid BSR(vol of BL / Yield
vol of solid) (%)
Chloroform 0.93 85
Toluene 0.93 84
Cyclohexane 1.06 71

Particle Morphology

When cyclohexane is used as bridging liquid the particles of the low sieve size fraction
(280-450µm) are somewhat irregular whereas the particles of the upper sieve size fraction
(1400-1600µm) are completely spherical (Fig 3). All particles from the experiment where toluene
is used as bridging liquid are completely spherical (Fig 4a & b).

a) 280-450µm.32x b) 1400-1600µm.16x
Figure 3: Particle morphology of different sieve fractions at 200C: Benzoic acid conc. = 0.375
g/ml, N=600 rpm, feeding rate =1.7ml/min, BSR (Cyclohexane) = 1.06.

a) 450-800µm.25x b) 1250-1400µm.20x
Figure 4: Particle morphology of different sieve fractions at 200C: Benzoic acid conc. = 0.375
g/ml, feeding rate =1.7ml/min, N=600 rpm, BSR (Toluene) = 0.93.
When chloroform is used as bridging liquid the particles change from thin and irregularly shaped
agglomerates to more dense and spherical agglomerates with increasing particle size (Katta and
Rasmuson 2008). Only particles >630 µm are spherical agglomerates. The smaller particles are
either thin, irregularly shaped agglomerates or fragments from larger agglomerates. Clearly, the
selection of the bridging liquid has a significant influence on the morphology of the product
particles and on the overall degree to which the product appear as spherical agglomerates.

Mechanical strength analysis

Average fracture stress of the 30 particles from different experiments and different sieve
fractions are presented in Figure 5. The fracture stress of the particles is changing with the
bridging liquid used (Fig 5). The particles have a high fracture stress for toluene as bridging
liquid and low value of fracture stress for cyclohexane.
Fracture stress (MPa)

0.3
0.25
0.2

0.15
0.1
0.05
0
1 2 3

Bridging liquid

Figure 5: Fracture stress for particles from different bridging liquids: Benzoic acid conc. =0.375
g/ml, N= 600rpm, feeding rate= 1.7ml/min, at 200C: (BSR=0.93), 1. Chloroform, 2. Toluene, 3.
(BSR=1.06) Cyclohexane

In Fig 6 the compression characteristics of single and a bed of agglomerates, are presented and
compared. In the first compression-release cycle, the single agglomerate using toluene as the
bridging liquid only recover 41 µm out of the 1012 µm total compression, i.e. only 4 % and the
elastic recovery for chloroform is 3%, and for cyclohexane is 6%. In comparison, the elastic
recovery of a bed of particles from an experiment using toluene as bridging liquid is 28 %, and
the corresponding values for chloroform is 21 %, and for cyclohexane is 16%. In the second
compression-release cycle the elastic recovery in all cases is much higher. Several single
particles and beds of particles from different sieve fractions have been studied, and overall the
result is that for single particles the initial elastic recovery is below 6% and for beds it is 15 -
30%. As 100% elastic recovery denotes the complete elastic material, spherical agglomerates
produced in this work has very low elastic recovery. The particles are clearly plastic in their
compression. It is generally believed that to create strong compacts, i.e. a tablet, either a
plastic deformation or an extensive fragmentation of the particles must occur (Sandell et al.,
1993).

120
Elastic Recovery (%)

Chloroform_ single
100
Chloroform_bed
80
Toluene_ single
60
Toluene_bed
40
Cyclohexane_single
20
Cyclohexane_bed
0
1 2 3 4
Compression run

Figure 6: Repeated compression of the single agglomerates and bed of the particles from sieve
fraction 1000-1250µm: Benzoic acid conc. = 0.375 g/ml, N=600 rpm, BSR: Chloroform &
Toluene=0.93, Cyclohexane =1.06.

Table 2: Compression of the agglomerates from different bridging liquids

Sample Toluene Chloroform Cyclohexane

Compressibility Index 33.5 46.6 38.4

A weak and easily compressed bed is signified by a high value of the compressibility index. The
compressibility index for bed of the particles is in the range of 30-50% (Table 2). When
chloroform is used as bridging liquid, the particles show high compressibility. Even though the
load used for bed compression is very low the particles have shown a significant compressibility.

4. Conclusions

Spherical agglomerates of benzoic acid can be prepared by using different bridging liquids. The
choice of the bridging liquid has an influence on the physico mechanical properties of the
particles. The particle size distribution is changing with the bridging liquid used. Particles
prepared from toluene as bridging liquid are completely spherical. Low elastic recovery and high
compressibility of the spherical agglomerates are found to be favorable for direct tabletting.
5. Notations

BSR Volume of bridging liquid

Volume of solid
F Force [N]
σ Stress [MPa]
d Diameter [m]
He Recovered size [m]
Hc Minimum size [m]
Hi Initial size [m]
H Height of the bed [m]
ER Elastic recovery ratio [%]
V Volume [m3]
ρ Density [kg/m3]

6. References

[AMA02] Amaro-Gonzalez, D., Biscans, B., 2002. Spherical agglomeration during

crystallization of an active pharmaceutical ingredient, Powder Technology. 128 188-194

[FAR61] Farnand J.R., Smith H.M., and Puddington I.E., Spherical agglomeration of solids in
liquid suspension. Can.J.Chem.Eng. 39, No.4, 94 – 97, 1961.

[KAT08] Katta, J., Rasmuson, Å. C., 2008. Spherical Crystallization of benzoic acid. Int. J.
Pharmaceut. 348, 61-69.

[KIR92] Kirk-Othmer., Kroschwitz, J.I., Howe – Grant, M., (EDS.), Encyclopedia of chemical
Technology, vol 4, fourth ed. John Wiley & Sons, New York, 1992.

[SAN93] Sandell, E., Industrial Aspects of Pharmaceutics. Swedish pharmaceutical press,

Stockholm, Sweden, 1993, p 142