In Situ Ultrasonic Attenuation Spectroscopic Study of the Dynamic Evolution of Particle Size during Solution-Phase Crystallization of Urea Patricia Mougin,†,# Derek Wilkinson,*,† and Kevin J. Roberts‡
CRYSTAL GROWTH & DESIGN 2003 VOL. 3, NO. 1 67-72
Centre for Molecular and Interface Engineering, School of Engineering and Physical Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, UK, and Institute for Particle Science and Engineering, Department of Chemical Engineering, University of Leeds, Leeds LS2 9JT, UK Received September 3, 2002;
Revised Manuscript Received October 10, 2002
ABSTRACT: In situ ultrasonic attenuation spectroscopy is used to examine the batch crystallization of urea from supersaturated aqueous and methanolic solutions. Benchmarking studies carried out on three cases are presented: noncrystallizing milled urea crystals in sunflower oil suspension, crystallizing pure urea from aqueous solution, and crystallizing urea in the presence of biuret habit modifier from methanol solution. In all cases, the technique was found to be capable of monitoring the size and concentration of anisotropic urea particles and it was responsive to the length and width of the needle-shaped crystals up to its upper size limit of 1000 µm. From measurements of changing particle size and concentration during crystallization, mass and linear crystal growth rates were calculated. Introduction Crystallization from solution is a routine unit operation used in the fine chemicals industry for purification and separation of products such as pharmaceuticals, agrochemicals, and speciality chemicals including dyes and pigments. Industrial production of these high valueadded materials usually involves batch rather than continuous manufacturing processes in which high product quality and process reproducibility are prerequisites for market success. This requires close control of the governing process parameters such as mother liquor supersaturation during crystallization, crystallinity, and polymorphic form of the product, as well as regulation of the product crystal size distribution (CSD) and its evolution over time due to growth. Given the inherently nonlinear and time-dependent growth environment within batch crystallizers, adequate monitoring and hence control of the process can only be accomplished by using appropriate analytical methods capable of characterizing the significant process parameters on-line during processing. Controlling CSD is particularly important as it is a major factor dictating product behavior downstream through its impact on operations such as filtration, drying, transport, and storage. Furthermore, the ability to control particle size at the primary particle formation step would facilitate process intensification by removing the need for secondary processing through, e.g., comminution to satisfy customer CSD requirements. However, on-line measurement of CSD can be difficult since * Communicating author: Derek Wilkinson, School of Engineering and Physical Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS UK. Ph +44 (0)131 451 4717. Fax +44(0)131 451 3129. E-mail:
[email protected]. † Centre for Molecular and Interface Engineering, School of Engineering and Physical Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, UK. ‡ Institute for Particle Science and Engineering, Department of Chemical Engineering, University of Leeds, Leeds LS2 9JT, UK. # Current address: SSCI, Inc., 3065 Kent Avenue, West Lafayette, IN 47906 USA.
many commercially available particle sizing methods rely on light scattering. These techniques are inherently ill-suited to examining the high concentration crystal/ solution slurries found in batch crystallization processes. As these particle sizing methods cannot operate at such high solid concentrations, a difficult and time-consuming sampling and dilution step is needed, a process that can lead to significant modification of the CSD as well as delaying access to the result. Ultrasonic attenuation spectroscopy (UAS) is a characterization technique that is suitable for measurement of particle sizes in the range 0.01-1000 µm. It is capable of examining optically opaque or concentrated systems without any dilution1 and so is attracting attention as a useful technique for characterizing concentrated suspensions. However, the complex theory relating ultrasonic attenuation spectra to CSD is a significant obstacle to its routine application for dynamic characterization in particle processing, especially in cases such as crystallization in which the physical parameters of the liquid medium and the particles may vary over the course of the process. This paper describes in situ UAS experiments in which the crystallization of urea and the influence of the habit modifier biuret were followed and from which calculations were made of the mass and linear growth rates of the crystals formed. Acoustic Attenuation Spectroscopy When a sound wave passes through a particulate suspension in liquid, changes occur to the wave as well as to the two phases of the medium. A particle presents a discontinuity to sound propagation and the wave is scattered with a redistribution of its acoustic energy throughout the volume (scattering and diffraction losses). In addition, absorption phenomena occur such as viscous losses, taking place as the particles move relative to the suspending medium, and thermal losses associated with temperature gradients occurring at the interface between particles and the suspending medium.
10.1021/cg025578u CCC: $25.00 © 2003 American Chemical Society Published on Web 11/01/2002
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Figure 1. Schematic of the experimental arrangement for recording ultrasonic, turbidimetric, and temperature data during temperature-programmed cycles.
The relative importance of the various absorption mechanisms depends on thermophysical properties of the component phases, the ultrasound frequency, and the concentration and size of the particles. Attenuation of an ultrasonic wave passing through a suspension may be modeled, given a set of mechanical, thermodynamic, and transport properties describing both the suspending and suspended media. In this work, the CSD was derived from ultrasonic attenuation measurements using the wave scattering theory of Epstein and Carhart2 and Allegra and Hawley3 (ECAH). ECAH theory models the influence of a single spherical scatterer of a given particle size on a continuous ultrasonic wave. By summation over the ensemble of particle sizes, the ultrasonic attenuation associated with any particle size distribution may be calculated, thus facilitating data inversion of experimental attenuation spectra into particle size distribution data. The physical properties of both phases required to implement the ECAH model in full are (i) velocity of the ultrasonic wave; (ii) density; (iii) thermal expansion coefficient; (iv) heat capacity; (v) thermal conductivity; (vi) attenuation of the ultrasonic wave; (vii) viscosity of the fluid phase and shear rigidity of the solid phase.
Ltd.) operating over the frequency range 1-150 MHz and capable of characterizing particles in the size range from 0.01 to 1000 µm. The instrument uses two pairs of transducers to span the broad frequency range. The attenuation coefficient measured as a function of frequency is defined as
Materials and Methods
Urea Particle Size Benchmarking. Some of urea’s physical properties (ultrasound attenuation, speed of ultrasound, elastic properties, thermal conductivity) are direction-dependent. As the mathematical model used to derive CSD information from acoustic attenuation spectra is based on isotropic spherical particles, average values of the physical parameters describing urea were taken, and some deviations were expected because of the nonspherical shape of urea particles. Although urea is well characterized compared to other organic crystals, some of its physical properties were not available from the literature, notably, the speed of ultrasound and attenuation of ultrasound within solid urea. For this study, these physical properties were
Experimental Systems. Urea (formula CO(NH2)2, molecular weight 60.06) crystals are highly anisotropic, mainly due to strong intermolecular N-H‚‚‚O hydrogen bonds that ensure cohesion within the crystal lattice resulting in a chainlike structure. When grown from pure solutions, urea crystallizes as long needles with a length/breadth ratio (aspect ratio) varying from 10:1 to 50:1. The presence of a habit modifier such as biuret (formula NH(CONH2)2, molecular weight 103.08) during crystallization can result in crystals with much smaller length/breadth ratios.4 Biuret is a byproduct of urea synthesis so it is usually present in small proportions in unpurified urea product. Ultrasound Attenuation Measurements. Measurements were carried out using an Ultrasizer (Malvem Instruments
a)
()
I0 1 ln ∆L I1
where a is the attenuation coefficient, I0 and I1 are the incident intensity and the intensity after passing the distance ∆L through the sample. ∆L can be adjusted between 0.8 and 100 mm to optimize signal-to-noise ratio according to the attenuation characteristics of the sample. The instrument’s sample chamber is 2.8 L in volume with a heater and marine propeller type stirrer. A platinum resistance thermometer and additional cooling coils connected to a water bath (Haake F3) were fitted in the instrument’s chamber. To monitor the onset of crystallization, turbidity was measured using a fiber optic probe (Sybron Brinkmann Lexan) connected to a colorimeter (Brinkmann PC700). Sensor outputs were monitored by a computer interface which controlled the temperature in the sample chamber and the water bath as well as logging temperature and turbidity data (Figure 1).
Results and Discussion
Solution-Phase Crystallization of Urea
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Table 1. Physical Parameters of Urea Crystals and Sunflower Oil at 20 °C property
sunflower oil
urea
density (kg/m3) sound speed (m/s) thermal dilation (1/K) thermal conductivity (J/(m s K)) heat capacity (J/(kg K)) shear rigidity (N/m2) viscosity (N s/m2) attenuation (dB/m) at f (MHz)
5.65 × 102 1.453 × 103 7.1 × 10-4 1.7 × 10-1 2.0 × 103
1.33 × 103 4.11 × 103 1.2 × 10-4 9.9 × 10-1 1.5 × 103 4.3 × 109 4 × 10-4 f2
6.6 × 10-2 8.5 × f1.8
Table 2. Physical Parameters of Aqueous and Methanol Solutions property density (kg/m3) sound speed (m/s) thermal dilation (1/K) thermal conductivity (J/(m s K)) heat capacity (J/(kg K)) viscosity (N s/m2) attenuation (dB/m) at f (MHz), T (°C)
aqueous solution
methanol solution
1.14 × 103 1.73 × 103
8.85 × 102 1.50 × 103
10-4
10-3
2.6 ×
1.2 ×
6.0 × 10-1
2.15 × 10-1
3.7 × 103
2.5 × 103
2.6 × 10-3 (-7.9 × 10-3T + 0.38) f(2.7 × 10-3T + 1.9)
2.8 × 10-3 (-7.9 × 10-3T + 0.768) f1.96
estimated from elastic constants (speed of ultrasound) or “guestimated” based on experience with similar materials in the case of the attenuation of ultrasound. The model was tested on dispersions of sieved particles of milled urea crystals dispersed in sunflower oil. Particle size calculated using these physical properties agreed well with size measurements of diluted suspensions by laser diffraction indicating that these parameters were appropriate. Other physical data were obtained from the literature.5-7 The data used in particle characterizations are summarized in Table 1 for urea crystals and sunflower oil at 20 °C and in Table 2 for urea solutions. Crystallization of Urea from Aqueous Solution. Urea was crystallized from a 55.5 w% solution in water (saturated at 30 °C) in the sample chamber of the ultrasonic spectrometer. This solution was cooled from above 30 °C down to 20 °C at 0.1 °C/min. Turbidity was monitored simultaneously during the cooling of the solution to detect the formation of crystals. As crystallization proceeded and ultrasound attenuation increased, it was necessary to limit the maximum frequency of the measurement to remain within the instrument’s measurement range. Figure 2 compares turbidity data recorded during cooling with ultrasound attenuation measurements at 10 MHz. The onset of crystallization was detected by turbidity at 24.9 °C, earlier than it was detectable by acoustic attenuation (24.5 °C). When a monomodal log-normal distribution was assumed to describe the CSD, the inversion procedure resulted in a high residual and the solid concentration was overestimated compared to the concentration expected on the basis of solubility data. Assuming a bimodal distribution resulted in acceptably low residuals and reasonable solid concentration results. This is significant since the model describes concentration as
Figure 2. Comparison of turbidity and acoustic attenuation data at 10 MHz for determining onset of crystallization of urea from aqueous solution when cooling at 0.1 °C/min.
Figure 3. Evolution of the CSD during crystallization of urea from aqueous solution.
well as CSD so if either result is wrong then there can be no confidence in the other result either. Conversely, obtaining a realistic result for solid concentration increases confidence overall in the accuracy of the ultrasonic technique. Comparing the geometric means of the two modes of these bimodal distributions with the primary dimensions of the crystals observed in microscope images revealed that the bimodal description of the distribution was indicative of the shape of the crystals. The smaller geometric mean of the distribution was consistently close to the width of needlelike crystals, while the relation between the geometric mean of the larger mode and length of needles depended on the size of the needlelike crystals. Figure 3 shows the evolution of the CSD during crystallization of urea. The spectrum measured at 24.3 °C, 16 min after the beginning of crystallization as assessed by turbidity measurements, is the latest spectrum that could be analyzed. The inversion software failed to resolve subsequent spectra. It can be seen in Figure 3 that the larger mode is progressing toward 1000 µm, the upper size limit of the instrument. Progress of crystal length beyond the upper size measurement limit of the instrument was confirmed by microscope images (Figure 4) taken at the end of the crystallization.
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Figure 4. Microscope image of typical urea crystal grown from aqueous solution.
Figure 5. Evolution of CSD during crystallization of urea from methanol solution at 28.5 w% (g of urea/g of methanol) in the presence of 3 w% of biuret.
Crystallization of Urea in Methanol in the Presence of Biuret. Results obtained when measuring crystals within the instrument’s size range indicated that the bimodal nature of the distribution was due to the needlelike habit of urea crystals rather than artifacts of the data inversion process. To facilitate further investigation of on-line measurement of shape and size
Mougin et al.
of crystals, urea was crystallized from methanol in the presence of biuret, a well-known habit modifier8 of urea. Crystallization of urea in methanol was carried out using a 28.5 w% solution (g of urea/g of methanol) in the presence of 3 w% of biuret (g of biuret/g of urea). The solution was cooled from 40 °C down to 15 °C at 0.4 °C/min. Under these conditions, the estimated final concentration based on solubility data for urea in methanol is 6.9 v%, assuming that biuret has a negligible effect on solubility. Figure 5 shows the evolution of the CSD of urea crystals forming in the presence of biuret. The first curve (31.4 °C) shows a broad monomodal distribution changing into a bimodal distribution in all the subsequent distributions. The CSD was found to vary little after the initial monomodal stage of the crystallization process, whereas the solid concentration increased steadily throughout (Figure 6). After the initial stage, temperatures below 27.6 °C, the recovered CSD was consistently bimodal. The ratio of modes of the distributions was found to be roughly constant throughout the process at approximately 3.1: 1. Comparisons with microscope images, an example of which is presented in Figure 7, showed that the two modes of the reported distributions were close to the primary dimensions of the suspended crystals, within the limits of the accuracy of size analysis by microscopy. As in the case of the crystallization of pure urea from aqueous solutions, these results did not describe the CSD in terms of equivalent volume spheres, but reflected the primary dimensions of the crystals. Although the measured size was roughly constant from early on in the process, the solid concentration increased steadily, suggesting that nucleation occurred throughout the process. The fact that subsequent growth of these nuclei was not detected in the size analysis (i.e., small particles corresponding to the growing nuclei were not observed) could be due to analysis of the attenuation spectra by a model which is limited to a maximum of two log-normal distributions. Since the nonspherical product crystals were described by that bimodal distribution, the presence of a small volume fraction of small particles could
Figure 6. Evolution of mean size and solid concentration during crystallization of urea from methanol solution with 3 w% of biuret and quadratic polynomial fit of concentration.
Solution-Phase Crystallization of Urea
Figure 7. Microscope image of urea crystals crystallized from methanol solution with 3 w% biuret.
not be included in the solution. The use of a modelindependent analysis or a model allowing for a third mode could possibly reveal the presence of growing nuclei. Taking the geometric means of the bimodal distributions as approximations of the width and length of the crystals and modeling the particles as rectangular parallelepipeds of width a and length b, the diameter of the equivalent volume sphere was calculated. Measured crystal concentration and calculated volume equivalent diameter as a function of time are presented in Figure 6. There was no significant change in the volume equivalent diameter after the first two minutes of the crystallization. A polynomial fit of degree 2 was found to describe well the evolution of the solid concentration (Figure 6). These solid concentration data can easily be converted to a measure of the solute concentration at any time t:
c(t) ) c(0) - FsCs(t) where c is the solute concentration (mass of solute per unit of volume of solution), Fs is the solid-phase density, and Cs is the volumetric concentration of crystals. The profile of solute depletion is plotted in Figure 8. This shows the variation of solute concentration c(t) along with the variation of solubility due to temperature change during the crystallization. The comparison shows that the solute concentration profile follows the
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solubility curve closely, indicating that the crystallization was carried out at very low supersaturation throughout. Figure 8 shows that for the cooling rate used (0.4 °C/min), supersaturation remains constant during the crystallization process until complete solute depletion, reflecting the small metastable zone width of urea in methanol, leading to nucleation throughout the process. From the evolution of solute concentration and crystal size during crystallization, the overall apparent linear growth rate Ga was calculated. As this rate takes into account the mass increase due to nucleation, it differs from the simple crystal growth rate G which corresponds to the mass increase due to growth alone. The overall linear growth rate can be written:
Ga )
FsDeq dCs 3Cs dt
where Cs is the solid concentration, Fs is the density of the solid particle, and Deq is the volume equivalent sphere diameter. Figure 9 shows the evolution of the apparent overall linear growth rate Ga and supersaturation as a function of time. It can be seen that the supersaturation remained roughly constant at σ ) 0.019 ( 0.003 up to t ) 41 min, at which time the minimum temperature was achieved. This indicates that the depletion of solute concentration due to growth and nucleation followed closely the generation of supersaturation due to cooling. When cooling stopped, the supersaturation level decreased. The supersaturation range derived from solid concentration data is similar to published results by Davey et al. for the crystallization of urea in the presence of biuret,5 typically in the range 0.005-0.025. The reported widthwise growth rate of single crystals for a comparable biuret concentration yielded values in the range 0.5 × 10-7 to 1.5 × 10-7 m/s within this supersaturation range, comparable to the values found for Ga within the same supersaturation range even though Ga accounts for nucleation.
Figure 8. Comparison of desupersaturation profile with solubility during crystallization from methanol solution in the presence of 3 w% biuret.
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conditions, it was seen that the particle size distributions obtained by data inversion of ultrasonic attenuation spectra gave some insight into the shape of the formed crystals. Supersaturation conditions and overall mass increase rate data were derived from the correlation between solid concentration and particle size data. It was found that the desupersaturation profile followed the saturation curve closely, i.e., that the crystallization occurred at very low levels of supersaturation. These results suggested the presence of nucleation throughout the process, possibly reflecting the small metastable zone width of urea under these conditions.
Figure 9. Evolution of the overall linear growth rate during crystallization of urea from methanol solution with 3 w% biuret.
Conclusions Initial studies of static suspensions were carried out to assess ultrasound sizing applied to a dispersion of milled urea crystals in sunflower oil. These showed that problems arising from anisotropy of urea crystals could be circumvented by using averaged physical properties. Minor deviations from sphericity did not cause any significant problems measuring these milled crystals. The dynamics of urea crystallization from aqueous solution were followed by thorough physical characterization of the liquid medium allowing for property changes due to variations of temperature and solute concentration during the crystallization process. Continuous sizing of the long needlelike urea crystals was not possible toward the end of the crystallization process as they grew to lengths beyond 1000 µm, the maximum size range limit of the instrument. However, within that restriction, it was possible to characterize nonspherical particles. Studying crystallization of urea from methanol solution in the presence of the habit modifier biuret showed that the evolution of solid concentration and particle size distribution could be characterized successfully from ultrasonic attenuation measurements. In this process, the size of the crystals did not vary significantly from an early stage of the crystallization, suggesting continuing nucleation with cooling of the solution. Under these
Acknowledgment. This work, which forms part of the Ph.D. work of one of us (P.M.),9 was carried out as part of the Chemicals Behaving Badly initiative, a collaborative project funded by EPSRC (GR/L/68797) with industrial support from Astra Charnwood, BASF, Glaxo-Wellcome, SmithKline Beecham, ICI, Malvern Instruments, Pfizer, and Zeneca. We gratefully acknowledge all members of this academic/industrial team, notably, the industrial coordinator Professor L. J. Ford, for their contributions to the project. We are also grateful for the helpful suggestions of the reviewers. References (1) Alba, F. U.S. Patent 5,121,629, 1992. (2) Epstein P. S.; Carhart R. R. J. Acoust. Soc. Am. 1953, 25, 553-565. (3) Allegra, J. R.; Hawley, S. A. J. Acoust. Soc. Am. 1972, 51, 1545-1564. (4) Anwar, F. The Assessment of Urea-Related Compounds as Nonlinear Optical Materials and the Single-Crystal Growth of Urea and NN′-Dimethylurea, Ph.D. Thesis, University of Strathclyde, 1988. (5) International Critical Tables; Washburn, W., Ed.; McGrawHill: New York, 1926-1930. (6) Perry’s Chemical Engineers’ Handbook, 6th ed. Green, D. W., Ed.; McGraw-Hill Chemical Engineering series, 1984. (7) McClements, D. J. The Use of Ultrasonics for Characterising Fats and Emulsions, Ph.D. Thesis, University of Leeds, 1988. (8) Davey, R.; Fila, W.; Garside, J. J. Cryst. Growth 1986, 79, 607-613. (9) Mougin, P. In Situ and On-line Ultrasonic Attenuation Spectroscopy for Particle Sizing during the Crystallisation of Organic Fine Chemicals, Ph.D. Thesis, Heriot-Watt University, 2001.
CG025578U
