Cryst. Res. Technol. 42, No. 6, 583 – 588 (2007) / DOI 10.1002/crat.

200610867

Study of lactose crystallization in water-acetone solutions

A. B. N. Brito*1 and M. Giulietti1,2

1
Federal University of Sao Carlos - Chemical Engineering Department - Industrial Crystallization
Laboratory - Rod. Washington Luís Km 235 - P.O. Box 676 - CEP:13565-905 - Sao Carlos-SP, Brazil
2
Laboratory of Chemical Process and Particle Technology of Institute for Technological Research - Av.
Prof. Almeida Prado 532 -Universitary City - CEP:05508-901 - Sao Paulo-SP, Brazil

Received 13 November 2006, revised 1 February 2007, accepted 8 February 2007

Published online 10 May 2007

Key words crystallization, lactose, acetone.

PACS 61.66.Hq

This paper describes a study on the process of lactose crystallization using a water-acetone solution. The
selection of lactose was based on its significance for the pharmaceutical and food industries and on the fact
that the crystallization of this organic compound has been little studied and is, unlike inorganic compounds,
complex. The objective was to achieve lactose batch crystallization of solutions by analyzing the crystal
growth under different operating conditions. To determine solubility curves, the experiments were carried out
based on gravimetric methods. All the crystallization experiments were performed according to the
methodology proposed by Nývlt in 1985, who uses the temperature at which the first crystals appear
(nucleation) to establish the width of the metastable zone and the induction time. The results showed that
crystals with different average diameters, shape factors, and recovered mass were obtained for different
water-acetone compositions.

© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

1 Introduction
In previous studies, Nickerson and Moore studied lactose rate crystallization [1] and factors that influence
lactose crystallization [2]. Thurlby and Sitnai investigated some process alternatives for lactose crystallization
[3]. According to Mullin [4], every crystallization process achieved from a solution is characterized by the
formation of supersaturation, nucleation and crystal growth, as well as secondary phenomena, including
aggregation, agglomeration, breakage, redissolution and ageing. One of the ways to separate organic products
from aqueous solutions is adding non solvent compounds that reduce the solute solubility without creating a
new liquid phase [5]. Therefore it is possible to imagine that crystal formation will occur differently when one
of the solvents is changed which may provide information that may improve the industrial productivity of this
high added value product. Among the numerous organic products, lactose was chosen because this product has
received great industrial interest for the production of baby powdered milk, sweeteners and pharmaceutical
products [6]. The goal was to perform lactose batch cooling crystallization of water-acetone solutions by
analyzing the crystal growth under different operating conditions.
Solubility and saturation A given amount of solvent provides the dissolution of a maximum quantity of
solute at a given temperature, forming a saturated solution. This solute concentration in the saturated solution is
called solubility [7, 8]. The solubility curve of a substance in any solvent is represented by the solubility
variation according to the temperature. Nývlt et al. [7] describes two methods to determine the solubility
experimentally: the polithermic method and the isothermal one. The polithermic method involves the
____________________

* Corresponding author: e-mail: abnbrito@iris.ufscar.br

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584 A. B. N. Brito and M. Giulietti: Study of lactose crystallization in water-acetone solutions

preparation of a solvent-solute mixture of known composition, initially with solute in excess in a closed
container, kept under agitation and heating with 0,1 K increment. This solution is heated softly until the
crystals have dissolved completely, and then is transferred to cool until the nucleation. After that, the
temperature is increased in 0.2 K/min until the dissolution of the last crystal in the equilibrium temperature.
Already the isothermal method consists in maintaining the temperature of the solution contends excess of solid,
adding small amounts of solvent, in regular intervals, watching the disappearance of crystals.
Nucleation and supersaturation The supersaturation state is an obligatory requirement for all
crystallization operations and may be attained by various methods, including cooling, heating, evaporation or,
when required, by addition of a less efficient solvent that is miscible with the original solvent. The nucleation,
the step that initiates the crystallization process, involves the appearance of crystals from a supersaturated
solution. Nucleation can be regarded as a process that establishes the size of the crystalline product and also
performs a significant function to establish its physical properties and the crystal purity [9].
Growth There are many theories related to crystal growth, some of which are reported in Mullin [4],
Nývlt [9] and Chernov [10]. The ratio at which the crystal size increases can be represented by its growth speed
in the perpendicular direction to the crystal face (linear growth rate). Different faces of a crystal can grow at
different rates; the average growth rate can be approximately calculated by the increase of a sphere diameter
having the same volume as the crystal or by the increase of characteristic crystal dimension.

2 Materials and methods

Materials In all the experiments, monohydrate lactose (C12H22O11.H2O), PA acetone, both brand named
ANIDROL and distilled water were used. In the experiments, the following instruments were utilized:
- 125 mL glass jacket reactor with propeller stirrer and speed control;
- Thermostatic bath Polystat 12101-20;
- Malvern Mastersizer Microplus MAF5001;
- Olympus model BX60 Optical microscope;
- Bronzinox Sieves manufactured by Telas Metálicas e Sintéticas Ltda.
The experiments were carried out at the Crystallization Laboratory at the Chemical Engineering Department of
UFSCar - Federal University of Sao Carlos.
Methodology For the solubility experiments, it was used a variation of the isothermal method reported by
Myerson [11], in the following way: it was weighed a given lactose mass in the reactor, then it was added
water and acetone at previously defined ratios; this suspension was heated with a thermostatic bath and was
kept at the same temperature for 5 h; the solid lactose excess was vacuum filtered, and dried for 24 h at room
temperature; gravimetry was used to establish the solubility for each specified temperature, by varying the
water-acetone ratio.
For crystallization kinetics experiments, proposed by Nývlt [9], the laboratory methodology basically
consisted in adding to the jacketed glass reactor an amount of the solution of lactose in water with a known
concentration. Then this solution was heated with a thermostatic bath under continuous agitation with a
propeller stirrer connected to a velocity controller. This solution was heated at approximately 15.0 K above the
saturation temperature, to ensure that there would be no lactose crystals in the solution. After this step, the
solution was slightly cooled at a temperature that remained above the saturation temperature; acetone was
added, recording the cooling time before and after nucleation. Then the solution was cooled to very low
temperatures and the batch time - elapsed time from the appearance of the first crystal until the end of the
experiment - was recorded. Finally, the entire content of the reactor was vacuum filtered. The obtained crystals
were weighed after drying for 24 h at room temperature in a desiccator. The operating conditions of these
experiments are described in table 1.
Crystallized mass analysis The granulometric distribution of the crystallized solid was carried out with
Malvern Mastersizer Microplus MAF5001 instrument. The functional principle of the Malvern is based on a
laser diffraction that measures particle size. A particle size corresponds to the diameter of the equivalent sphere

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Cryst. Res. Technol. 42, No. 6 (2007) 585

- sphere having the same volume as the particle. Results are reported as a percentage of the total volume of the
particles in the distribution. The refraction index utilized for lactose was 1.361 [12]. The crystals were
submitted to sieving for granulometric analysis. For that purpose, it was used Bronzinox sieves whose meshes
are described in table 2.

Table 1 Operating conditions for the crystallization kinetics experiments. (*VR1 - Cooling rate before nucleation.).
Stirring Heat. Rate Lactose Mass Initial Conc. Heating Cooling VR1*
Experiment
(rpm) (K/min) (g) (g/100 g solv) Temperature (ºC) Temperature (ºC) (K/min)
1 350 1.38 7.46 27.16 70 20 0.61
2 350 0.92 7.46 27.02 70 20 0.36
3 350 1.83 7.46 27.17 70 20 1.39
4 350 0.48 7.46 27.16 70 20 0.29
5 350 0.43 7.46 27.02 70 20 0.22
6 350 0.93 7.46 27.17 70 25 0.25
7 350 0.87 7.46 27.15 70 35 0.47
8 350 0.77 7.16 26.29 65 20 1.15
9 350 1.05 7.16 26.33 65 25 1.00
10 350 0.84 7.16 26.31 65 30 0.29
11 350 0.73 5.94 22.55 55 10 0.91
12 350 1.30 5.94 22.89 55 20 0.91
13 350 1.00 5.94 22.85 55 25 0.45

Table 2 Characteristics of the Sieves in the series ABNT P-EB 22.

Sieve Mesh (mm) Sieve Mesh (mm)
35 0.500 140 0.106
40 0.425 170 0.090
45 0.355 200 0.075
50 0.300 230 0.063
70 0.212 270 0.053
80 0.180 400 0.038
100 0.150 bottom 0
120 0.125

Sieving was performed by dividing the 14 sieves into two sets. Each set was kept under vibration for 20 min
and the material passing through the previous sieve was transferred to the next sieve. In the end, the sieves
were weighed and the masses corresponding to each granulometric range were established. After sieving, some
fractions from the samples were separated and analyzed with an Olympus model BX60 optical microscope
which was coupled to a video that transmitted the photo-micrographies with tenfold magnification to a
computer.
For each of the experiments performed, it was established the volumetric shape factor required to calculate
the parameters of the lactose crystallization kinetics. It was sieved the crystallized mass and separated the
granulometric fraction corresponding to meshes 140 and 170 which had an average diameter of 98 µm.
Approximately 50 crystals of this diameter range were separated and weighed. From these data, the shape
factor was calculated using equation 1:
mc
α= .ρ c .N c , (1)
( Dm )
3

where α is the volumetric shape factor, Dm is the average diameter of the two sieves, mc is the crystal mass, Nc
is the number of crystals counted between sieves and ρc is the crystal density, equal to 1.54g/cm3 [13].
Nývlt et al. [7] consider that the precipitated crystal mass (mc) is given by the material balance and the
crystal number (Nc) affects the medium crystal size (Lm), according to equation 2:
2
mc = .N c .α .ρc . ( Lm ) .
3
(2)
9

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586 A. B. N. Brito and M. Giulietti: Study of lactose crystallization in water-acetone solutions

To establish growth rate of the crystals (G), equation 3 was used.

L
G= , (3)
z.t
where L is the crystal size, t is the crystallization time and z is the crystal dimensionless size. For L=Lm
(medium crystal size), z=3 according to Nývlt et al. [7].
The crystal yield (Y) was calculated with equation 4.
mc
Y (%) = .100 (4)
Lactose mass

3 Results and discussion

Figure 1 shows a comparison between the results of the solubility experiment and those obtained by other
authors’ results: Mullin [4], Jelen and Coulter [14], Thurlby [15], Garnier [16] and Mc Loughlin et al. [17].

Fig. 1 Lactose solubility in water (experimental data Fig. 2 Lactose solubility in water-acetone at different
compared to other authors). temperatures.

Fig. 3 Lactose-water-acetone triangular diagram Fig. 4 Granulometric distribution performed on Malvern for
experiments 5, 6 and 7.

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Cryst. Res. Technol. 42, No. 6 (2007) 587

It was possible to see that the experimental results are better adjusted to the curves reported by Mullin [4] and
Jelen and Coulter [14]. Figures 2 and 3 show lactose solubility data in water and acetone mixtures at different
ratios and temperatures. Both figures show that lactose solubility is directly proportional to temperature and
inversely proportional to acetone concentration. Lactose solubility in pure acetone is very close to zero.
Malvern granulometric analyses are shown in figures 4 to 6. It can be seen that the average and maximum
crystal sizes varied with each experiment. Table 3 shows yield values, crystal sizes and crystal growth for
acetone crystallization experiments.

Fig. 5 Granulometric distribution performed on Malvern for Fig. 6 Granulometric distribution performed on
experiments 8, 9 and 10. Malvern for experiments 11, 12 and 13.

Table 3 Results from crystallization experiments with acetone.

mc Final conc. Theat Tsat TNucl Tfinal tb VR1 VR2 Yield Lm G
Exp.
(g) (%) (ºC) (ºC) (ºC) (ºC) (s) (K/min) (K/min) (%) (µm) (µm/s)
1 6.62 12.01 70 44.95 50 20 12360 0.61 0.15 88.74 65.40 0.0052
2 6.91 11.67 70 44.95 50 20 10500 0.36 0.17 92.63 51.37 0.0055
3 6.70 11.34 70 44.95 45 20 7140 1.39 0.21 89.81 48.05 0.0070
4 6.83 11.56 70 44.95 50 20 6660 0.29 0.27 91.55 61.23 0.0094
5 6.46 11.53 70 44.95 50 20 3540 0.22 0.51 86.60 61.07 0.0175
6 3.54 6.16 70 44.95 50 25 2880 0.25 0.52 47.45 82.45 0.0252
7 3.10 5.36 70 44.95 50 35 1980 0.47 0.45 41.55 99.59 0.0441
8 5.28 9.15 65 43.66 50 20 2940 1.15 0.61 73.74 86.10 0.0258
9 3.14 5.46 65 43.66 50 25 1500 1.00 1.00 43.85 66.50 0.0427
10 5.90 10.24 65 43.66 50 30 2700 0.29 0.44 82.40 66.77 0.0240
11 3.31 5.77 55 37.02 45 10 3180 0.91 0.66 55.72 116.01 0.0285
12 2.43 4.33 55 37.02 45 20 1260 0.91 1.19 40.91 82.68 0.0598
13 3.45 6.16 55 37.02 45 25 2400 0.45 0.50 58.08 164.20 0.0480

In table 3, mc is the crystal mass, T is the temperature, tb is the batch time, VR1 and VR2 are cooling rate before
and after nucleation, respectively, Lm is the average crystal size and G is the crystal growth rate. It is possible
to see that for experiments 1, 2, 4 and 5, whose initial supersaturation was constant and whose yields were
close to 90%, increased batch time did not influence the average crystal sizes and these continued virtually
constant. For experiments 8 to 10, whose initial concentration was lower than those in previous experiments,
an increase in the batch time caused an increase in average crystal sizes. For the experiments whose
temperature variation was constant (experiments 1 and 8 or 9 and 12, for instance), it can be seen that a
reduction in the saturation caused an increase in average crystal sizes. For experiments 5 to 7, a reduction in
the batch time caused an increase in average crystal sizes, probably due to agglomeration of lactose crystals, as
can be seen in figure 7. Figure 8 shows a photo-micrography of the fines fraction in experiment 7 with acetone
addition. In this figure, it is possible to see the “tomahawk” shape of the lactose crystals.

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588 A. B. N. Brito and M. Giulietti: Study of lactose crystallization in water-acetone solutions

Fig. 7 Photo-micrography of the experiment 5. Fig. 8 Photo-micrography of the sample

retained in mesh 50 sieve, experiment 7.

4 Conclusions
Regarding reported results, it is possible to conclude:
• When submitted to a shorter batch time and consequently lower temperature variation, the yield was lower.
As result it is possible to infer that the metastable zone width for lactose is larger than 30K.
• When submitted to batch time that was above 6,000s, no significant variation took place in crystal sizes and
yield.
• A higher supersaturation caused larger crystals when they were submitted to shorter batch time.
Crystallization speed is proportional to the supersaturation. However if this speed is too high, agglomerates
may develop. Agglomeration appears as an increase to the size and a reduction to the number of crystals
and it depends on the crystallization system.
• Cooling the solution must be done slowly so that no agglomeration develops and a maximum yield is
obtained in crystal formation.

Acknowledgements The authors wish to thank to CAPES and FAPESP for financial support.

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