On the Crystal Polymorphic Forms of L-Glutamic Acid Following Temperature Programmed Crystallization in a Batch Oscillatory Baffled Crystallizer Xiong-Wei Ni,*,† Andrew Valentine,† Anting Liao,† Sylvie B. C. Sermage,† Gillian B. Thomson,† and Kevin J. Roberts‡
CRYSTAL GROWTH & DESIGN 2004 VOL. 4, NO. 6 1129-1135
Centre for Oscillatory Baffled Reaction Applications (COBRA), School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK Institute of Particle Sciences and Engineering, Department of Chemical Engineering, School of Process, Environmental and Materials Engineering, University of Leeds, Leeds LS2 9JT, UK Received May 28, 2004;
Revised Manuscript Received August 27, 2004
ABSTRACT: L-Glutamic acid exhibits two polymorphs: the metastable R form that is prismatic in nature and the stable β form that is needle shaped. In this paper, the effects of mixing intensity, cooling rate, and temperature on the polymorphism and crystal characteristics in a solution crystallization of L-glutamic acid are investigated in a relatively new oscillatory baffled crystallizer. The prevalence of a preseeding effect was identified during the experiments, whereby traces of a specific polymorph were retained between experiments and acted as seeding for subsequent batches despite rigorous cleaning procedures. Under those conditions, the variations in mixing, cooling rate, and temperature seemed to have little effect on the polymorphic forms of the crystals prepared. Potential mechanisms for the preseeding effect are discussed. Examination of the role of seeding on the crystal morphology reveals its function to decouple the effect of preseeding, allowing the selected polymorph to be produced. Introduction Solution crystallization is a widely used process in the chemical and pharmaceutical industries for achieving a desired size, shape, and chemical nature of the product material. Controlling these properties presents a major challenge to industry since they influence considerably further processing factors such as powder flow, comminution, and solubilization. There are generally two stages in the formation of crystals: nucleation and growth. The process of nucleation involves the formation of new crystals in a crystallizing environment, and layer-by-layer addition of solute to nuclei is termed as the growth.1 Although there appears to be different mechanisms at which nucleation can occur, the most important mechanism is that of collision breeding, i.e., when a crystal touches another crystal or any other solid object, e.g., the walls of a crystallizer, fresh nuclei are readily produced.2 The on-set process of nucleation can exhibit very fast kinetics and is often too fast to control in a reliable manner. On the other hand, the subsequent growth of crystals post-nucleation is dependent on mass transfer where the solution must be transferred by turbulent mixing to the crystal surface and then takes part in the surface crystallization process.3 Consequently, the state of the mixing in a given crystallizer is an important factor in controlling the uniformity of the crystal sizes as well as serving to keep crystals in suspension throughout the process and in some cases prevents segregation of the supersaturated solution from causing excessive nucleation.4 Several authors have shown that by varying the mixing conditions, precipitates with different crystal size distributions and/ * Corresponding author. Tel: 44 131 451 3781; fax: 44 131 451 3129; e-mail:
[email protected]. † Heriot-Watt University. ‡ University of Leeds.
or morphologies can be produced5,6 and that the induction period to nucleation was decreased in all the systems tested.7,8 One of the objectives of this work is to examine the effect of mixing intensity on the crystal characteristics of L-glutamic crystals as prepared using an oscillatory baffled crystallizer (OBC). L-Glutamic acid is one of the naturally occurring R-amino acids, which form important building blocks for protein assembly as well as being used as food additives for taste; for example, monosodium glutamate is an indispensable additive for dehydrated soup and many other processed foods and has been widely marketed for cooking or table seasoning in Asian countries, the United States, and Latin America. Amino acids also have applications in the medical and cosmetics industries. The L-glutamic acid has two crystal polymorphs: R and β,9 of which β is the stable form, while R is metastable.10 Figure 1 shows the solubility as a function of temperature for these two polymorphs revealing, as expected, higher solubility for the crystallized form from aqueous solution.11 While both crystal forms exhibit a prismatic growth morphology, the β form crystals have a much greater aspect ratio, being needle-shaped in practice. At high temperatures (>45 °C) and given sufficient time, total dissolution of the R form and regrowth of the β form occurs, as a result of a solutionmediated transformation.10 Isolation of the stable β form is relatively easy through slow cooling.10,12-14 Obtaining the metastable R form is possible through rapid cooling to a set point well below 45 °C.10,15 Below this temperature, the solution-mediated transformation is retarded and the R form should persist. Clearly, the temperature and cooling rates have a significant effect on crystal morphology, which forms the second objective of this work and the results will be compared with that in a stirred tank crystallizer (STC).
10.1021/cg049827l CCC: $27.50 © 2004 American Chemical Society Published on Web 10/15/2004
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Figure 1. Solubility profiles of R and β forms of L-glutamic acid.
Traditionally industrial crystallization has been carried out in STCs, and this work is the first extensive experimental study on the crystallization of L-glutamic acid using an OBC. The OBC generally consists of a column containing periodically spaced orifice baffles with an oscillatory motion superimposed onto the flow. The mixing in an OBC is provided by the generation and cessation of eddies when flow interacts with baffles.16-18 With the repeating cycles of vortex formation, the strong radial velocities give uniform mixing in each inter-baffle zone and cumulatively along the length of the column.19-24 The fluid mechanical conditions in an OBC are governed by two dimensionless groups, namely, the oscillatory Reynolds number (Reo) and the Strouhal number (St), defined as
Reo )
2π fxoFD µ
(1)
D 4πxo
(2)
St )
where D is the column diameter (m), F is the fluid density (kg m-3), µ is the fluid viscosity (kg m-1 s-1), xo is the oscillation amplitude (m), and f is the oscillation frequency (Hz). The oscillatory Reynolds number describes the intensity of mixing applied to the column, while the Strouhal number is the ratio of column diameter to stroke length, measuring the effective eddy propagation.25 The product 2πfxo is the maximum oscillatory velocity (m s-1). The power dissipation rate, , in an OBC can be evaluated via a quasi-steady-state approach taking into consideration the effects of static, inertial, and frictional forces, assuming that there is a uniform velocity throughout the column:26,27
OBC )
(
)
2FNb 1 - R2 3 3 P ) xo ω (W kg-1) FV 3πC 2 R2 D
(3)
where P/V is the power density per unit volume (W m-3), Nb is the number of baffles per unit length of OBC (m-1), CD is the coefficient of discharge of the baffles () 0.7 normally), and R is the baffle free area ratio, defined as (Do/D)2, where Do is the orifice hole diameter (m). 1. Experimental Setup and Procedure 1.1 OBC Reactor Setup. A schematic diagram of the experimental OBC used in these experiments is shown in Figure 2. The OBC consists of a jacketed glass column of 75
Figure 2. Schematic diagram of OBC set up.
Figure 3. Shape of transmittance versus temperature for an aqueous solution at 45 g L-1 in an OBC. mm in internal diameter and 340 mm in height, providing a total volume of 1.5 L. The jacketed column is of 105 mm in diameter. The inlet and outlet of the jacket are connected to a temperature-controlled Haake (F3-CH) thermostat bath. Such a unit can provide a temperature within an accuracy of (0.1 °C, which ensures the exact supersaturation level in the crystallizer. An inbuilt pump ensures the steady flow of water through the OBC jacket. The temperature of the water bath is controlled either locally by manually selecting a set-point temperature or through an external computer control to provide a programmed linear cooling profile. The temperature of the solution within the OBC was monitored by a minute disk thermocouple and displayed on a desktop monitor. A reflective transmittance turbidity probe28 was fitted internally to monitor the turbidity in the bulk fluid. The readings from both the thermocouple and turbidity probe are logged by a computer. Figure 3 shows the shape of the turbidity response in one of the crystallization experiments. The diamond symbols indicate the temperature of dissolution, and the square symbols refer to the temperature of crystallization. Analyzing the turbidity readings allows the onset of dissolution/crystallization to be determined. The onset of crystallization may be observed with a 10% drop in transmittance from the maximum, while the onset of dissolution may be observed with a 10% rise in transmittance from the minimum. The 10% allows a margin of error with respect to transmitter noise. Two stainless steel (316 grade) orifice baffles (fractional free area of 0.19 and baffle spacing of 112.5 mm) were fitted close to the internal wall of the column, and were supported by two thin stainless steel rods and connected to a top disk where it joins a bearing and a motor. The frequency of oscillation from 1 to 8 Hz was controlled via a speed controller on the motor
Polymorphic Forms of L-Glutamic Acid
Figure 4. Temperature of crystallization and dissolution versus cooling rate in an OBC. and the amplitude of oscillation from 1 to 12 mm was achieved by adjusting the off-center position of the connecting pin in a flying wheel. 1.2 Crystallization Protocol and Product Characterization. In a standard experiment, 45 g of l-glutamic acid (Sigma-Aldrich) was added to the OBC of 1 L of distilled water to give a solution concentration of 45 g L-1 corresponding to a saturated solution at 65 °C. The oscillation frequency and amplitude were preset to a desired value. The solution was then heated, under a computer-controlled linear heating profile, to a temperature of 80 °C and held for an hour to ensure complete dissolution. The solution was then cooled at the same rate to 15 °C to induce crystallization. For experiments requiring rapid cooling, the solution was heated and held in a similar fashion, but the water bath was then emptied and filled with cold tap water, and the set-point temperature was manually set to 15 °C. At the end of each experiment, a sample of the resultant aqueous crystal solution slurry was taken and analyzed under a light microscope at between 10 and 40× magnifications to assess the crystal form and the approximate particle size. For experiments where the crystal size distribution was required, the remainder of each crystallized batch was filtered and the dewatered cake was dried in an oven at 30 °C overnight to remove any remaining moisture. The dried crystals were then suspended in propanol and their mean crystal size and crystal size distribution were assessed using a Malvern Mastersizer (Malvern Instruments).
2. Results and Discussions 2.1 Measured MSZW for OBC in Comparison to STC Data. The feasibility of applying OBC to the crystallization of L-glutamic acid was carried out29 for oscillation frequencies of 1, 2, and 3 Hz and amplitudes of 20, 30, and 40 mm at three cooling rates of 0.2, 0.5, and 0.67 °C min-1. A total of 26 experiments were performed. Figure 4 shows the dependence of the temperature of both dissolution and crystallization on the cooling rates in the OBC. The difference between these two temperatures, the metastable zone width (MSZW), reflects the nucleation barrier to growth, as in solution crystallization, crystals can only be formed when the temperature crosses the metastable zone, as illustrated by Figure 3. Hence the MSZW acts effectively the barrier for crystallization. It can be seen that the data reveal a slight dependence on nucleation rate consistent with a close match concentration increase, with cooling, to the subsequent nucleation process. Overall, the MSZW in the OBC increased fractionally
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Figure 5. Metastable zone width (MSZW) vs power dissipation in unseeded crystallization of L-glutamic acid (STC, stirred tank crystallizer). Table 1. Comparison of Operating Temperature for Both OBC and STC OBC
STCa
temp of dissolution (°C) 73-75 70 temp of crystallization (°C) 58 @ 0.2 °C/min 44-48 @ 0.2 °C/min 56 @ 0.5 °C/min 24-32 @ 0.5 °C/min aRefs
12-14.
or almost independent of the cooling rates. This would imply that the crystal growth in the OBC would be independent of the cooling rates. The result is striking. Figure 5 plots the MSZW against the power dissipation rate for both OBC and STC.12-14 Note that the power dissipation rate of an OBC can directly be calculated from eq 3. For an STC the following equation is used:30,31
ST )
P0N3Ds5 P (W kg-1) ) FV πD 2L/4
(4)
v
where P0 is the power number of the stirrer used, N is the speed of the stirrer, L is the liquid height, and Ds and Dv are the diameters of the stirrer and crystallizer, respectively. The graph shows that for the range of power dissipation rates, the MSZW in the OBC is relatively constant at about 15 °C, in comparison with that from 25 to 40 °C for the STC, indicating better control over such a crystallization process using the OBC. By looking at the temperature measurements in Table 1 for this crystallization process for both reactor types, it shows that the crystallization took place at a higher temperature (smaller MSZW) in the OBC than that in a STC, which will have a significant influence on nucleation rate and resultant morphology due to the lower supersaturation. It may be for this reason that only β-crystals were obtained in the OBC for all the operating conditions. This is intriguing, to say the least, and would indicate that the final form of crystals is largely independent of the operating conditions in the OBC, or in other words, the phase of the secondary nucleation is too short to allow any noticeable effect of mixing to take place. One important fact is that the results presented so far are directly opposite to that reported by Liang et al. in a STC,12-14 where the crystals
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Table 2. Experiments Carried out in OBC feasibility study number of experiments oscillation amplitude (xo) frequency (f) cooling rate (°C/min) temperature of dissolution (°C) final temperature (°C)
mixing, cooling rate and seeding
mixing and cooling rate
26
32
22
20, 30, 40 mm 1, 2, 3 Hz 0.67, 0.5 75 20
10, 15, 20, 40 mm 1, 2, 3 Hz 0.5, crash cooling 80 15
10, 15, 20 mm 1, 2 Hz 0.8, 1.0, 1.5, 1.7, 2, 2.2, 2.6 80 20
had predominately the R form for the same supersaturation levels and cooling rates. Clearly, the form of mixing in the two types of crystallizers is distinctly different, thus implying that the superior and more uniform mixing produced by the OBC is a major factor in defining the final form of crystals. If the hypothesis were valid, this would suggest that the mixing in the OBC was too strong to allow the R form to exist, as the R form is metastable, and β form is the stable one, or the intensity of oscillation would break up solutions clusters that perhaps template R phase formation in a STC; hence, the metastable phase never forms or becomes dominating in an OBR. The result of a much smaller MSZW in the OBC would appear to validate such a claim. Alternatively, it could be the preseeding effect where residues of crystal seeds from previous runs might be present. 2.2 Effect of Variation in the Mixing Intensity. Recent work in the USA32,33 showed that by varying the mixing intensity in a STC it enabled isolation of the metastable form of one industrial crystal by preventing the attainment of the necessary Gibbs free energy to overcome the change to the stable form. On the basis of the outcome of Li’s work, it was anticipated that by decreasing the mixing intensity in the OBC, it would be possible to prevent the attainment of the necessary Gibbs free energy to drive the solution-mediated transformation from the metastable R to the stable form β. Ten further experiments were subsequently carried out in the OBC at much lower oscillation intensity using oscillatory frequencies of 1, 2, and 3 Hz and peak-topeak oscillatory amplitudes of 10, 15, and 20 mm.34 These combinations gave a range of power dissipation rates between 0.03-5.6 W kg-1. Note that experiments using mixing intensities below this range were not initially conducted as crystals failed to be fully suspended in solution. A linear cooling rate of 0.5 °C min-1 was used. Once again none of these experiments yielded the metastable R form, with the stable β form obtained exclusively. In comparison, the studies in a STC12-14 produced crystals of predominately R form. The operations in the STC ranged from 200 to 500 rpm, corresponding to the power dissipation rates of 0.88-13.67 W kg-1.30,31 To ensure that the mixing intensities used in the OBC experiments were simply not low enough to obtain the R form, one further experiment was performed where no fluid oscillation was provided at all. However, this strategy was also unsuccessful. As a result, the findings of Li32,33 did not hold in the experiments performed here. Variation in the mixing intensity would thus appear to have little effect on polymorphism in the solution crystallization of L-glutamic acid in the OBC. 2.3 Effect of Cooling Rate and Final Solution Temperature. In earlier STC studies, the metastable R form was readily obtained by using faster or crash
cooling.10 Kitamura also indicated that the solutionmediated transformation rate, from R to β, in the STC was dependent on the temperature. At temperatures below 45 °C, the transformation was sufficiently retarded to allow crystallization of the R form. It was therefore further believed that the choice of the cooling rates and the final target temperature would also prevent the solution-mediated transformation from occurring. To confirm these postulates in the OBC, a series of new experiments were designed and performed. Faster cooling rates of 0.8, 1, 1.5, 1.7, 2, 2.2, and 2.6 °C min-1 were used in the experiments at oscillation amplitudes of 10, 15, and 20 mm, oscillation frequencies of 1 and 2 Hz, and the final temperature of 20 °C.35 Table 2 lists the experimental conditions used. From the results of a total of 22 runs, once again only β form crystals were obtained in the OBC. Further nine experiments were carried out using crash cooling.34 The experimental procedures were broadly similar to those used in the mixing intensity work. Early experiments attempted to use the water bath to crash cool by manually setting the target temperature of 15 °C and allowing the bath to reach this temperature rapidly. However, some experiments performed showed that the cooling rate afforded by the bath was not sufficient. Therefore, in later runs, the water bath was heated to 80 °C as normal but then quickly emptied and filled with cold tap water at around 15 °C to offer a much more rapid cooling effect. It should be noted that in using such a method, the cooling rate is not linear with time and currently there is no available instrument that enables us to measure such large rates. As a result, we are unable to report the exact value for the crash cooling. To examine the additive effects of the cooling rate and mixing intensity, the latter was varied over some of the crash cool experiments, particularly to investigate the effect of supplying no oscillation at all in the OBC on the crystal morphology. However, in contrast to the work of Kitamura, this strategy did not result in the isolation of any R form. The final crystal slurry was composed exclusively of β form crystals. A further experiment was performed using a solution that was saturated at a temperature below 45 °C, and this also failed to produce the desired R form. Some of the early experiments were repeated, with small samples being evacuated from the OBC at regular intervals during cooling and then analyzed to monitor the progress of crystal morphology during a typical experimental run. Figure 6 shows that the metastable R form was indeed produced in the early stages of the cooling phase in the OBC, but these crystals were then steadily dissolved and transformed into stable β form crystals, confirming the presence of the solution-mediated transformation in the OBC. In summary, it would
Polymorphic Forms of L-Glutamic Acid
Crystal Growth & Design, Vol. 4, No. 6, 2004 1133
Figure 6. Solution-mediated transformation over time in the OBC.
appear that the effects of the temperature and cooling rate on the crystal morphology witnessed in the crystallization of L-glutamic acid in STC were not observed using the OBC. 2.4 Potential Effect of Preseeding. The fundamental question remains: why are the L-glutamic acid crystals obtained in the OBC exclusively of β form, despite lower and sometimes no fluid oscillation as well as when faster and crash cooling were used? Could there be a preseeding effect in the OBC? The role of preseeding was then investigated as a potential driver for the observed total transformation from the R to β form in our earlier work as well as this work. It was hypothesized that miniscule fragments of β crystals were being retained in scratches in the glass OBC and/or stainless steel baffle surfaces and acting as seeds in subsequent batches, leading to a severe slow-down of the β-phase nucleation and persistence of the metastable R form. If this mechanism did exist, it would be likely to take precedence over any other mechanisms affecting nucleation, including the effects of mixing intensity, cooling rate, and temperature examined in our studies. To verify this hypothesis, more rigorous cleaning procedures were adopted and the results of the subsequent crystallization experiments analyzed. From this, a sodium hydroxide solution (0.1 M) was first used to wash the reactor between batches in the hope of neutralizing any remaining L-glutamic acid fragments. Subsequent crash cooling crystallization runs were then
repeated, but from these yielded no R form crystals were found. A much more aggressive specialized alkaline glass cleaner, Pyroneg (manufactured by Johnson Diversey), was then employed to clean the glass, and this also made no difference to the form of the crystals formed in the OBC. The results suggest that the preseeding effect exists, and is difficult to be removed. 2.5 Seeding Experiments and Associated Recrystallization. If the preseeding effect does exist in the OBC, the seeding should then decouple the impact of the preseeding. To test this assumption, we decided to actively seed the OBC with the R form seeding crystals and then examine the composition of consecutive unseeded batches. The procedure was as follows: a 45 g L-1 solution of L-glutamic acid was prepared and heated to around 10 °C above its saturation temperature, i.e., 80 °C. The system was then crash cooled to a temperature of 15 °C under moderate agitation (15 mm and 2 Hz, giving ) 0.7 W kg-1). Shortly after the cooling began, as the temperature entered the R form metastable zone (∼58 °C), 5 g of the R form seed crystals were added into the batch to induce secondary nucleation. Observations revealed that crystallization of the R form occurred immediately and examination of the final crystal slurry separated from the mother liquor at 15 °C revealed that the R form was obtained exclusively. Thus, the formation of the metastable R form crystals via R phase seeding within the OBC (Figure
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cleaning regime used, it would appear that some R crystals had been retained between the batches and had effectively seeded the next batch. The nucleation cluster sizes are generally very small, ca. 1-10 µm and such nano-/micro-particles will adhere to reactor internals, particularly polished steel, which has a polar surface coating of oxide that would bind a polar amino acid molecule. Due to the small sizes, these would be resistant to cleaning procedures. As the number of consecutive batches increased, the proportion of the R form decreased and the proportion of β form increased dramatically, allowing more β crystals to be retained and to act as the seeds for next batch. In the end, generally after four repeated runs, β form crystals were found to dominate in the OBC. In summary, the preseeding effect would appear to occur with respect to either polymorph, and in the case of the β form, this would go some length in explaining the inconsistent results between ours and similar STC studies. Once the polymorphic form is changed, it cannot be reversed. However, the question remains as to why the form of L-glutamic acid crystals obtained in the OBC differed from that in the STC for similar operational conditions. It should be noted that nucleation kinetics depend on materials; for instance, the stainless steel and Perspex STCs exhibited different nucleation kinetics,14 and thus different polymorph behaviors would be expected. However, the same material was used in both the STC12 and our work, and we would expect the same/ similar nucleation kinetics in the two systems. Would the difference in the total area or volume of the internals exposed to the supersaturated solution in the two types of crystallizers be an issue? To assess this, the relative surface areas of baffles used in this study and the retreat curve impeller in the STC studies12-14 were calculated, giving 11 921 mm2 in the STC versus 16 342 mm2 in the OBC. Intuitively, a larger surface area should provide more sites for crystal fragments to attach themselves on as the seeds for subsequent batches. However, it remains an open question as to whether the difference of 27% in the surface area of the internals between the two reactor designs would be significant enough to explain the different polymorphic forms produced in the two systems. Figure 7. Optical micrographs showing (a) metastable R form crystals obtained through seeding using R form seeds; (b) increase in the proportion of β form crystals obtained after first subsequent unseeded recrystallization; (c) further increase in the proportion of β form crystals obtained after a second subsequent unseeded recrystallization.
7a) provides conclusive evidence in support of the preseeding effect. The rig was then cleaned using Pyroneg, and a second subsequent experiment was carried out without the presence of R seeding crystals. The final slurry was analyzed and it was shown that the crystals were predominately of R form, albeit with the presence of some β crystals (Figure 7b). After the use of a further cleaning procedure using Pyroneg, further crystallization was performed. This resulted in a mixture of R and β crystals; however, the proportion of the R form was significantly reduced (Figure 7c) in comparison to these shown in Figure 7a. Therefore, despite the rigorous
Conclusions From the extensive studies on solution crystallization of L-glutamic acid in OBC, the following conclusions can be made: (i) Neither reduction nor elimination of the mixing intensity in the OBC resulted in formation of the R form in contrast to the work of Li in the USA.32,33 The stable β form of L-glutamic acid was obtained exclusively in these experiments in the OBC. (ii) The solution-mediated transformation from the R to β form was observed in the OBCs. This agrees with the findings of Kitamura in similar STC studies.10 (iii) Increasing the cooling rate from 0.5 to 2.6 °C min-1 and further to a rapid crash cool did not result in formation of the R form of L-glutamic acid. This contradicts the findings from similar study albeit using a STC reactor.10,12-14 (iv) R Form crystals were successfully crystallized in the OBC via secondary nucleation by seeding the batch
Polymorphic Forms of L-Glutamic Acid
with a known amount of R crystals. The crystals were added when the temperature of the solution was within the R metastable zone as measured by Kitamura.10 The lifetime and the effect of such seeded crystals was found to decrease sharply as a function of successive cleaning/ re-crystallization cycles. (v) The mechanism for preseeding effect in OBCs is presumed to reflect the retention of miniscule fragments of crystals from previous batches perhaps retained within the surface roughness of the reactor internals (walls, baffles, etc.) of the OBC with this material, acting as seeds for any subsequent batches, this despite the adoption of rigorous cleaning procedures. This appeared to be true for both R and β crystal forms. This phenomenon may have more to do with the materials of construction used rather than the hydrodynamics of the system. Clearly, further work is required to further test this postulate and to identify the mechanism for the differences in polymorphic forms produced in the OBC and STC reactors under very similar operating conditions. Nomenclature CD D Do Ds Dv L N Nb P/V P0 Reo St xo R µ F
coefficient of discharge of the baffles [) 0.7 normally] column diameter [m] orifice hole diameter [m] diameter of a stirrer [m] diameter of a crystalliser [m] liquid height [m] speed of the stirrer [rad min-1] number of baffles per unit length of OBC [m-1] power density per unit volume [W m-3] power number of the stirrer used [-] the oscillatory Reynolds number [-] the Strouhal number [-] oscillation amplitude [m] baffle free area ratio, defined as (Do/D)2[-] power density [w kg-1] fluid viscosity [kg m-1s-1] fluid density [kg m-3]
Acknowledgment. The authors wish to thank the EU’s ERASMUS exchange scheme for the financial support for Miss Sermage, the Heriot-Watt University for the support for Mr. Valentine and Miss Liao and Dr. Xiaojun Lai for helpful discussions. References (1) Mullin, J. W. Crystallisation, 3rd ed.; Butterworth-Heinnemann, Woburn, MA, 1993. (2) Kitaigorodsky, A. I. Order and Disorder in the World of Atoms; Mir Publishers: Moscow, 1980. (3) Klug, D. L. Handbook of Industrial Crystallisation; Myerson, A., Ed.; Butterworths: New York, 1993. (4) Weissbuch, I.; Leiserowitz, L.; Lahav, M. Crystallisation Technology Handbook; Mersmann, A., Ed.; Marcel Dekker: New York, 1995. (5) Liu, S. T.; Nancollas, G. H.; Gasiecki, E. A. J. Cryst. Growth 1976, 33, 11-20.
Crystal Growth & Design, Vol. 4, No. 6, 2004 1135 (6) Fitchett, D. E.; Tarbell, T. M. AIChE J. 1990, 36, 511-522. (7) Sohnel, O.; Mullin, J. W. Cryst. Res. Technol. 1987, 22, 1235-1240. (8) Bohlin, M.; Rasmuson, A. C. Can. J. Chem. Eng. 1992, 70, 120-128. (9) Hirokawa, S. Acta Crystallogr. 1955, 8, 637-641. (10) Kitamura, M. J. Cryst. Growth 1989, 96, 541-546. (11) Kitamura, M. J. Cryst. Growth 2002, 237-239, 2205-2214. (12) Liang, J. K. Process scale dependence of batch crystallised L-glutamic acid from aqueous solution in relation to reactor internals, reactant mixing and process conditions”, Ph.D. Thesis, Heriot Watt University, 2002. (13) Liang, K.; White, G.; Wilkinson, D.; Roberts, K. J.; Ford, L. J.; Wood, W. Ind. Eng. Chem. Res., manuscript submitted. (14) Liang, K.; Wilkinson, D.; White, G.; Roberts, K. J.; Ford, L. J.; Wood, W. Cryst. Growth Des. 2004, 4, 1039-1044. (15) Mougin, P.; Roberts, K. J.; Wilkinson, D. Cryst. Growth Des. 2002, 2, 3, 227-234. (16) Brunold, C. R.; Hunns, J. C. B.; Mackley, M. R.; Thompson, J. W. Chem. Eng. Sci. 1989, 44, 1227-1244. (17) Mackley, M. R.; Ni, X. Chem. Eng. Sci. 1991, 46, 31393151. (18) Mackley, M. R.; Ni, X. Chem. Eng. Sci. 1993, 48, 32933305. (19) Fitch, A. W.; Ni, X. Chem. Eng. J. 2003, 92, 243-253. (20) Ni, X. J. Chem. Technol. Biotechnol. 1995, 64, 165-174. (21) Ni, X.; Brogan, G.; Struthers, A.; Bennett, D. C.; Wilson, S. F. Trans. Inst. Chem. Eng. 1998, 76, 635-642. (22) Ni, X.; Sommer de Ge´licourt, Y.; Baird, M. H. I.; Rama Rao, N. V. Can. J. Chem. Eng. 2001, 79, 444-448. (23) Ni, X.; Jian, H.; Fitch, A. W. Chem. Eng. Sci. 2002, 57, 2849-2862. (24) Ni, X.; Jian, H.; Fitch, A. W. Trans. IChemE 2003, 81, 842853. (25) Ni, X.; Gough, P. Chem. Eng. Sci. 1997, 52, 3209-3212. (26) Jealous, A. C.; Johnson, H. F. Ind. Eng. Chem. 1955, 46, 1159-1166. (27) Baird, M. H. I.; Stonestreet, P. Trans. IChemE 1995, 73, 503-511. (28) Gerson, A. R.; Roberts, K. J.; Sherwood, J. N. Powder Technol. 1991, 65, 243-249. (29) Sermage, S. Crystallisation of L-glutamic acid in an oscillatory baffled crystalliser”, M. Philos. Thesis, Heriot-Watt University, Edinburgh, UK, 2002. (30) Holland, F. A.; Chapman, F. S. Liquid Mixing and Processing in Stirred Tanks; Reinhold Publishing Corporation: New York, 1966. (31) Bates, R. L.; Fondy, P. L.; Fenic, J. G. Impeller Characteristics and Power, In Mixing: Theory and Practice; Uhl, V. W., Gray, J. B., Eds.; Academic Press: New York, 1966; Volume 1, Chapter 3. (32) Li, Y.-E. Control of polymorphism of an active pharmaceutical ingredient during manufacture, Paper 107, Annual Meeting AIChE, Indianapolis, IN, November 3-8, 2002. (33) Li, Y. E.; Hengeveld, J.; Gandarilla, J. Crystallisation in polymorphic systems: control of transformation rate, Paper 18c, Annual Meeting AIChE, San Francisco, CA, November 16-21, 2003. (34) Valentine, A. “On characterisation of a solution crystallisation of L-glutamic acid in an OBC,” Report of final year research project, Heriot-Watt University, 2002. (35) Liao, A. “On crystallisation of L-glutamic acid in an oscillatory baffled crystalliser,” First year Ph.D. report, HeriotWatt University, Edinburgh, 2003.
CG049827L
