70 Ind. Eng. Chem. Res.

2006, 45, 70-75

Application of a Neural Network for the Prediction of Crystallization Kinetics

Meng Yang and Hongyuan Wei*
School of Chemical Engineering and Technology Tianjin UniVersity,
Tianjin, 300072, People’s Republic of China

A method for more-accurate prediction of crystallization kinetics is greatly needed in the field of industrial
crystallization. Traditional empirical correlations cannot give reliable predictions, because of the highly nonlinear
behavior of crystallization kinetics, although they have been used for a long time. In this paper, the development
of a neural network model is presented. The model was trained with limited data obtained from an anti-
solvent crystallization system (ciprofloxacin hydrochloride, H2O, and ethanol). The predictions from the network
then were validated against newly measured data. The results confirm that this approach gives much more-
accurate predictions of the kinetics, in terms of crystal growth and agglomeration as examples. The mean
relative error of the predicted growth rates from this model, versus the measured data, is generally <10%
and, in some cases, is as good as 5%. This is a significant improvement on the relative error of 20% or more
that is typically achieved by traditional correlations.

1. Introduction
The artificial neural network (ANN) has been developing for
many years and has an increasingly significant role across a
wide range of fields. ANN has been applied to chemical
engineering over the last 16 years. Since 1988, when Hosking
and Himmelblau1 first applied it to error diagnosis for a chemical
process, it has been widely used for various applications in
chemical engineering.2
Crystallization kinetics (e.g., nucleation rate or crystal growth)
is essential for the analysis, design, and operation of industrial
crystallization processes. Traditionally, kinetics is described by
correlations that are obtained from experimental data using
assumed functional forms. The mechanisms of nucleation and
crystal growth are extremely complex, with high nonlinearity
and parameter interactions, which are not easily reflected by
simple empirical correlations, so that the use of those correla-
tions normally leads to large errors in predictions. However,
the neural network approach is better able to reproduce the
overall system behavior, with its nonlinearities and parameter
interaction effects. It can not only capture the interactions
between each influential element but also provide the mapping
procedure from input to output, so it is expected to be able to
predict the complex interplays of the influential factors in
crystallization processes.
This paper describes the development of a neural network
model to predict crystal nucleation, growth, and agglomeration
rates. An anti-solvent crystallization system that is composed
of ciprofloxacin hydrochloride, H2O, and ethanol was used for
the purposes of training and validating the model.
2. Construction of the Network
Several papers have suggested that using a multiple-layer
neural network is a more effective way to approximate nonlinear
relationships between parameters.4-8 In fact, 80%-90% of ANN
applications use a multiple-layer neuron structure or derivatives
thereof.
Multilayered networks can perform well on any linear or
nonlinear problems and can approximate any reasonable function
* To whom correspondence should be addressed. Tel.:
+86 22 27405754. Fax: +86 22 27400287. E-mail address:
david.wei@tju.edu.cn.
10.1021/ie0487944 CCC: $33.50 © 2006 American Chemical Society
Published on Web 11/30/2005
very well. Such networks can overcome the problems associated
with linear and perception networks. The network constructed
in this work adopts such a multilayer structure, to approach a
function with definite discrete points. The training strategy of
the network is shown in Figure 1.
Determining a suitable learning rate for a nonlinear network
is important. A large learning rate may lead to instability.
Conversely, if the learning rate is too small, an unrealistically
long training time may be needed. Unlike linear networks, there
is no easy, prescriptive way of selecting a suitable learning rate
for nonlinear multilayer networks.
The network constructed in this work generalizes the Wid-
row-Hoff study rule; it trains the weightings of nonlinear
differentiable functions and is trained by input vector and target
vector pairs. The ANN model can finally approximate a function
that relates the input vectors to specific target vectors.
A multiple-layer neural network consists of input vectors,
hidden layers, and output layers. In the current work, the network
is constructed with two layers, which is believed to give
sufficiently good approximations for predicting kinetics.
The detailed structure of the network is illustrated in Figure
2, in which P is the input vector and the parameters b1 and b2
represent the hidden-layer and output-layer bias vectors, re-
spectively. N1 represents the hidden-layer parameter vectors,
which can be defined as
N1 ) W1P + b1 (1)
where W1 is the hidden-layer weighting matrix.
The hidden-layer propagation function, f1(x), is expressed as
2
f1(x) ) -1 (2)
1 + e-2x
Its purpose is to send information in the hidden layer to the
output layer. The output parameter, N2, can be calculated using
the following equation:
N2 ) W2P + b2 (3)
where W2 is the output-layer weighting matrix.
 Ind. Eng. Chem. Res., Vol. 45, No. 1, 2006 71

Figure 1. Training strategy of the constructed artificial neural network

(ANN) model.
Figure 3. Experimental setup. Legend: 1, crystallizer; 2, agitator; 3,
thermometer; and 4, thermostat.

weighed. A sample of the mother liquor was also analyzed, so

that the solution concentration and suspension density were
obtained. Crystal size distributions of samples were obtained
using a laser diffraction granulometer (Malvern Mastersizer).
Figure 2. Structure of the two-layer network. The experimental apparatuses are shown in Figure 3.

The definition of the output-layer propagation function, f2(x),

4. Experimental Data Analysis
is
The crystal growth rate (G) and nucleation rate (B0) are
f2(x) ) x (4)
calculated using the following equations with equilibrium data9
and y is the output vector. and experimental data:10

[ ]
In this application, supersaturation (S), temperature (t), volume
fraction (a), solid suspension density (Mt), and agitation rate dC(t) d ln V(t)
(Nstr) are defined as the input vectors (suspension density is - + (C(t) + Mt(t))
dt dt

[ ]
defined as the mass of solid particles per unit volume of slurry), G) (6)
whereas growth rate (G), nucleation rate (B0), and agglomeration n wti%
coefficient (Ka) comprise the output vectors. The use of the Mt(t) ∑
i)1 (L - Li)
tansig function (f1(x)) as the hidden propagation function, and i+1
the purelin function (f2(x)) as the output propagation function,
enable this network to approximate any function reasonably well. B0 ) n(L1,t) × G (7)
All weights and biases in the network are obtained through a
training procedure that is based on the measured data. After a The agglomeration coefficient (Ka) is the constant (assuming
predefined level of precision is achieved, the training procedure size independence) for describing the agglomeration rate (ragg),
can be terminated and the multiple-layer network is then ready as shown in eq 8 and can be obtained by discretizing population
to be used for prediction. balance:
To evaluate the accuracy of the network constructed, the
following mean relative error, Q, is used:

Q)
1 N

∑1 |
the prediction value - the experimental value
|
ragg ) Ka (∑
1 i-1
2 j)1
Ni-jNj - Nim0 ) (8)

N the experimental value

(5)
3. Experiments
The experiments were performed in a 6-L baffled crystallizer
agitated by a propeller at different stirring speeds, ranging from
250 rpm to 750 rpm. The diameter of the crystallizer is 18 cm,
and the height is 25 cm. The working volume in each run was
5 L. The temperature of the crystallizer was controlled by
recycling water from a thermal basin. In a typical run, a
preheated and filtered saturated aqueous solution of high-purity
ciprofloxacin hydrochloride was placed into the crystallizer. The
temperature of the crystallizer was maintained 5 °C higher than
that of the solution, to ensure that no crystals exist in the solution
prior to crystallization. After 0.5 h, the temperature of the
crystallizer was reduced to the saturation temperature of the
ciprofloxacin hydrochloride solution. A certain amount of seeds
was fed into the crystallizer before the batch experiment
commenced. Supersaturation was obtained by slow cooling. A
small amount of sample was removed and filtered at intervals
of every 15 min during the process. Particles were dried at a
temperature of 95 °C under vacuum conditions and then
5. The Traditional Correlation Approach for Kinetics
Predictions
The empirical correlation for predictions of crystallization
kinetics in the traditional format can be obtained through the
regression of experimental data, as shown in eqs 8 and 9. The
detailed descriptions for such method can be found in ref 11.
The format for linear growth rate (number-length coordinate)
in the traditional correlation is
E
G ) C exp - ( )
N d(S - 1)b
RT str
(9)
The constants C, E, d, and b can be obtained by a regression
procedure from experimental data. For this studied system, C
) 4.32 × 10-10, E ) 12761.3, d ) 0.887, and b ) 0.451. Figure
4 shows the predicted values (the solid line) coming from the
correlation developed by fitting the measured values against
measured data (depicted by solid dots). The mean relative error
(Q) can be up to 19.5%, which reflects the accuracy of the
prediction.
72 Ind. Eng. Chem. Res., Vol. 45, No. 1, 2006

Figure 4. Correlation between predicted and measured values of the growth

rate, G.

Figure 6. Correlation between predicted and measured values of the

agglomeration coefficient, Ka.

Figure 5. Correlation between predicted and measured values of the

nucleation rate, B0.

The nucleation rate, B0, can be regressed as the following

function:
Figure 7. Correlation between predicted and measured values of G.
B ) (5.29E + 17)(1 - a)
0 0.103
Mt0.932
Gv0.326
(10)
6. The Neural Network Approach for Kinetics
Predictions
The predicted values against measured data are shown in Figure
5. The mean relative error Q is 20%. The ANN model is sensitive to the number of neurons in its
The agglomeration coefficient, Ka, can be estimated by a hidden layers. Too few neurons may lead to underfitting.
semiempirical correlation, which is the function of fluid However, too many would contribute to overfitting, in which
conditions such as temperature, viscosity, and shear rate and is the fitting curve exhibits wild oscillations between well-fitted
assumed to have a function similar to that of the growth rate: training points. Hence, it is very important to select a suitable
number of neurons. After many trials, the model can give highly
7945.5
Ka ) (3.64E - 20) exp - ( RT )
Nstr0.448(S - 1)0.230
(11)
satisfactory results with 10 neurons in the hidden layer and 1
neuron in the output layer.
The weightings and biases in the model are as follows:
The predicted values against measured data are shown in Figure W1 ) [wij], where i is the number of input parameters and j
6. The mean relative error Q is 17%. is the number of neurons in the hidden layer
The experiments were also performed in two crystallizers with W2 ) [wij], where i is the number of output parameters and
different sizes (0.5 and 1.5 L), and data were regressed for the j is the number of neurons in the hidden layer
linear growth rate G, as shown in eq 12: b1 ) [bj], where j is the number of neurons in the hidden
layer
46329.5
G ) (5.579E - 3) exp - ( RT )
Nstr2.043(S - 1)0.349
(12)
b2 ) [bj], where j is the number of output parameters
The network was first trained with limited data obtained from
experiments, and predictions from the trained network were then
The predicted values against measured data are shown in Figure validated against newly measured data.
7. Very obviously, the error is even larger (Q > 40%). Network for Linear Growth Rate Prediction under the
To summarize the aforementioned comparisons, the traditional Number-Length Coordinate. The model constructed in this
approach for kinetic predications is not satisfactory and can lead case was trained with 31 sets of experimental data. Figure 8
to large errors. shows that the resulting correlation between the predicted values
 Ind. Eng. Chem. Res., Vol. 45, No. 1, 2006 73

Figure 8. Training the multilayer ANN network: correlation between the

experimental and predicted values of G.

Figure 10. Training the multilayer ANN network: correlation between

the experimental and predicted values of B0.

Figure 9. Multilayer ANN network prediction: comparison between the

experimental and predicted values of G.

Table 1. Validation: Experimental and Predicted Values of the

Growth Rate, G
Growth Rate, G (m/s)
experiment value predicted value
3.07 × 10-10 3.04 × 10-10
4.64 × 10-10 4.52 × 10-10 Figure 11. Training the multilayer ANN network: correlation between
4.97 × 10-10 5.64 × 10-10 the experimental and predicted values of Ka.
5.20 × 10-10 5.82 × 10-10
7.47 × 10-10 6.39 × 10-10 Table 2. Validation: Experimental and Predicted Values of the
9.54 × 10-10 1.00 × 10-9 Nucleation Rate, B0
Nucleation Rate, B0 (number/(m3 s))
(the solid line) and measured data (the open circles) is extremely experimental value predicted value
good. The mean relative error Q is only ∼1%.
2.17 × 1011 2.06 × 1011
Another six sets of experimental data were selected to validate 2.16 × 1011 2.16 × 1011
the model predictions away from training points. The experi- 2.30 × 1011 2.38 × 1011
mental value and the predicted values are shown as Table 1 3.27 × 1011 2.84 × 1011
and Figure 9. All predictions lie within 15% of the measured 3.00 × 1011 2.57 × 1011
2.789 × 1011 2.63 × 1011
values, with a mean relative error of Q ) 8.01%.
Network for Simultaneous Prediction of Nucleation Rate values and the predicted values for B0 and Ka are shown in
and Agglomeration Coefficient under the Number-Volume Tables 2 and 3, respectively, and, correspondingly, Figures 12
Coordinate. The model constructed in this case was trained and 13. The predicted values of B0 and Ka were within 15%
with 34 sets of experimental data. and 6%, respectively, of measured data, with corresponding
Figures 10 and 11 show the correlation between the predicted mean relative errors of 7.05% and 3.66%.
and measured values of B0 and Ka, respectively. The corre- Network for Growth Rate Prediction with Different
sponding mean relative errors are 9.42% and 5.8%. Crystallizers, under the Number-Length Coordinate. Two
Another six sets of experimental data were selected to validate sizes of crystallizers were used for the experiments; these had
the model predictions between training points. The experimental working volumes of 0.5 and 1.5 L.
74 Ind. Eng. Chem. Res., Vol. 45, No. 1, 2006

Figure 12. Multilayer ANN network prediction: comparison between the

experimental and predicted values of B0.

Figure 14. Training the multilayer ANN network: correlation between

the experimental and predicted values of growth rate.

Figure 13. Multilayer ANN network prediction: comparison between the

experimental and predicted values of Ka.

Table 3. Validation: Experimental and Predicted Values of

Agglomeration Coefficient, Ka
Agglomeration Coefficient, Ka (µm3/s) Figure 15. Multilayer ANN network prediction: comparison between the
experimental value predicted value experimental and predicted values of G.
3.38 × 10-20 3.22 × 10-20 Table 4. Validation: Experimental and Predicted Values of the
3.55 × 10-20 3.43 × 10-20 Growth Rate, G
4.50 × 10-20 4.24 × 10-20
3.27 × 10-20 3.26 × 10-20 Growth Rate, G (µm/s)
7.09 × 10-20 6.84 × 10-20 experimental value predicted value
7.37 × 10-20 7.08 × 10-20
2.91 × 10-5 2.93 × 10-5
2.59 × 10-5 2.61 × 10-5
The model constructed for this study was trained with 34 4.32 × 10-5 4.00 × 10-5
sets of experimental data. Figure 14 shows the correlation 4.62 × 10-5 4.60 × 10-5
between the predicted and measured values of G. The mean 5.49 × 10-5 5.46 × 10-5
relative error is Q ) 2%. 5.15 × 10-5 5.18 × 10-5
Another six sets of experimental data were selected to validate forms.3 Therefore, making use of these empirical correlations
the model predictions between training points. The experimental can lead to large errors.
and predicted values are shown in Table 4 and Figure 15. The mechanism of crystallization kinetics is very complex
Predicted values are within 7.5% of the experimental data, with with strong nonlinearity, which cannot be reflected accurately
a mean relative error of Q ) 1.73%. by a simple regression function. However, the neural network
approach is better able to reproduce overall system behaviors,
7. Conclusions with its nonlinearities and parameter interaction effects. It can
not only capture the interactions between each influential
Crystallization kinetics (such as crystal nucleation, growth, element but also provide the mapping procedure from input to
and agglomeration rates) is essential for the analysis, design, output. Its ability to predict the complex interplays of influential
and operation of industrial crystallization processes. The factors in crystallization processes result in more-accurate
traditional correlation approach for predicting kinetics is predictions of the crystallization kinetics, as demonstrated in
arbitrary and subjective in its selection of assumed functional this paper.
 Ind. Eng. Chem. Res., Vol. 45, No. 1, 2006 75

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Acknowledgment Tianjin, PRC, 2003.
The authors wish to acknowledge the National Natural
Science Foundation of China for financial support, and they ReceiVed for reView December 14, 2004
also thank Dr. Liu Yong (Tianjin University) and Dr. Simon ReVised manuscript receiVed October 25, 2005
Accepted November 3, 2005
Leefe (Chembridge Technologies, Limited, U.K.) for their
valuable assistance with this work. IE0487944