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Formation of Organic Particles Using a Supercritical Fluid as Solute
Chapter 6
Formation of Organic Particles Using a Supercritical Fluid as Solute 6.1 PARTICLES FROM GAS SATURATED SOLUTIONS Another high-pressure particle formation technique is the particles from gassaturated solutions (PGSS) process, which eliminates solubility limitations and large amounts of gas usage. The PGSS process can operate in both a batch or a continuous mode. This method was developed in 1995 by Weidner et al. [1e3] and is based on the fact that the solubility of compressed gas (usually sc-CO2) in a liquid substance and/or high-molecular weight substance (e.g., polymer) is much higher than the solubility of these substances in SCFs. A schematic representation of the PGSS process is given in Figure 6.1. In this particle formation process, CO2 is fed into a high-pressure vessel and dissolved in a molten substance at high pressure, leading to a gas-saturated solution combined with a viscosity reduction. After intensive mixing in a, e.g., static mixer, the solution is rapidly expanded through a nozzle into a spray tower to a lower (usually ambient) pressure. Thereby the CO2 evaporates from the droplets, which induces a high supersaturation and therewith solidification and particle precipitation due to the large temperature decrease. Thereafter, the solid particles are separated from the gas by means of a filter and a cyclone. In general, adjusting the process parameters, such as SCF concentration in the molten liquid, preexpansion temperature and pressure, nozzle geometry, and temperature and pressure in the spray tower, can control the product properties. Similar to the RESS process (Chapter 4), the knowledge of the SLG line of the substance of interest is important for the selection of the best operation conditions since the SLG line determines if the melted substance will form solid or liquid particles in the spray tower. A typical peT diagram for a binary CO2/poly-ethylene glycol (PEG) system is depicted in the left part of Figure 6.2 while in the right diagram, the influence of pressure on the mass fraction of PEG in CO2 is shown for a certain temperature [5]. It is obvious that with increasing the CO2 pressure, the PEG 4000 melting temperature, with Particle Formation with Supercritical Fluids. http://dx.doi.org/10.1016/B978-0-444-59486-0.00006-1 Copyright © 2014 Elsevier B.V. All rights reserved.
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FIGURE 6.1 Schematic diagram of particle processing by the PGSS technique [4].
FIGURE 6.2 Phase diagrams for the binary CO2/PEG 4000 mixture; experimental data are taken from Ref. [5].
the exception of low pressures (<1 MPa), decreases from 330 K at ambient pressure to 315 K at 8.2 MPa. In opposite thereto, the temperature is nearly constant for pressures between 8.2 and 20 MPa while at higher pressures, the SLG line increases again. Furthermore, at constant pressure, the CO2 concentration decreases with increasing temperature, and increases with increasing pressure for constant temperature. It is shown in the right diagram of Figure 6.2 for T ¼ 333 K that increasing the pressure from 0.4 to 28 MPa increases the CO2 mass fraction from about 0.07 to 0.28 [5].
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Typically the PGSS process operates at pressures in the range from 3 to 25 MPa and a CO2 consumption of 0.1e2 kg gas per kg solute [4]. Furthermore, the PGSS process allows forming particles from different kind of substances that need not to be soluble in sc-CO2, especially such polymers which are able to absorb large amounts (up to 40 wt%) of CO2. This process can also be applied for a mixture of active ingredient(s) and polymer(s) to produce composite particles. In addition, it is worthy to notice that in contrast to the common antisolvent techniques (Chapter 5), no organic solvent is required in the PGSS process. Compared to RESS, PGSS requires less-dense gas and a lower pressure which can lead to some economic advantages. However, both RESS and PGSS enable the production of a solvent-free powder.
6.2 MODIFICATION OF THE PGSS PROCESS While in the classical PGSS process a binary gas-saturated solution is expanded through a nozzle into a spray tower, all further developments of this process are characterized by processing at least three different substances. These basically identical processes are named as concentrated powder form (CPF), continuous powder coating spraying process (CPCSP), PGSS drying of aqueous solution (PGSS drying), and depressurization of an expanded liquid organic solution (DELOS). As described below, all these modifications are characterized by dissolution in the SCF in a premixed binary liquid mixture prior to the expansion of the ternary solution [6e9].
6.2.1 Concentrated Powder Form As a further development of the PGSS process, the CPF process has been proposed by Weidner et al. [10,11] in 1997. This process allows the generation of powders, which contain a very high content of liquids. Similar to the PGSS process, a dense gas is dissolved in a liquid substance and, after intensive mixing at high pressure, depressurized through a nozzle down to low pressure. Opposite to the PGSS method, a spray of fine droplets is formed during the expansion step of the gas-saturated liquid. At the same time and by means of an inert gas (e.g., N2), a powdered carrier compound is blown into the spray tower. Due to the expanding gas and the resultant high turbulent flow, both the droplets and the solid carrier are intensively mixed and solid agglomerates are formed. In case of a huge (i.e., high and wide) spray tower, a free-flowing powder that can contain up to 90 wt% (or more) of the liquid is formed [7]. The characteristics of the agglomerates are strongly influenced by the chemical and physical properties of the powdered carrier and the liquid. A detailed theoretical and experimental study shows that the bulk density of the carrier material is a suitable parameter to correlate the liquid uptake of the carrier [12]. For example, experiments show that silica with a bulk density of 50 g/dm3 are able to bind more than 90% of the liquid while a bulk density of
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200 g/dm3 leads to only 60 wt%. The reason therefore is mainly due to the much higher specific surface area of the silica with the lower bulk density. At this point, it should be considered that in opposition to the conventional PGSS process, particle precipitation does never occur. Depending on the properties of the carrier used, the highly dispersed agglomerates are formed either by penetration of the liquid into the porous carrier material or by simple agglomeration of the wetted less porous material.
6.2.2 Continuous Powder Coating Spraying Process Weidner et al. proposed a very interesting PGSS-based micronization process as an alternative technique for the manufacture of powder coatings [13]. Conventional coating techniques often require high temperatures and long residences times which may cause an unrequested decomposition that would destroy the product. The so-called CPCSP enables the processing of both conventional powder coating and (fast) reacting systems. In the CPCSP, each components of a powder coating mixture is melted in separate high-pressure vessels and high-pressure pumps fed both streams to a static mixer and are homogenized with dense CO2. As a consequence of the dissolved CO2, the mixture’s melting point is decreased which enables faster homogenization of the solution at lower temperatures. Now, similar to the other PGSS-based processes, the solution is expanded through a nozzle into the spray tower. Thereby fine droplets are formed which are cooled by the expanding gas. After crossing the solidification point of the liquid mixture (¼ SLG line, see left diagram of Figure 6.2), solid particles are formed. These particles can be separated from the gas by means of a cyclone and a filter while an exhauster removes the gas out of the spray tower. The product properties, mainly morphology of the powder, particle size, and size distribution, can be adjusted by the processing parameters such as saturation temperature and pressure. Experimental results show that lower saturation temperatures promote smaller particles with a narrower size distribution than higher temperatures. Increasing the saturation pressure results in smaller particles and a narrower size distribution which is mainly caused by the higher CO2 amount in the liquid solution (see right diagram of Figure 6.2) and hence higher dilution of the particulate phase in combination with faster cooling (Section 3.1).
6.2.3 PGSS Drying of Aqueous Solution Besides the applications described above, the so-called PGSS drying of aqueous solutions process can also be used for drying aqueous compounds (e.g., natural extracts such as green tea extracts) [14e18]. The process offers, compared to other drying processes such as spray-drying, some real advantages. It allows processing under gentle operation conditions which enables
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FIGURE 6.3 Schematic Tex,y diagram of a binary mixture. Depicted are the dew point curve (full line) and the bubble point curve (dashed line). Note that in case of the CO2eH2O mixture, T1 is equal to 373.15 K for p ¼ 0.1 MPa.
drying with reduced thermal degradation or contamination of the product. Furthermore, the process is carried out in a closed system under an inert gas (usually CO2) atmosphere. In a typical experiment, a static mixer is used to dissolve CO2 in an aqueous solution at pressures in the range from 10 to 15 MPa and temperatures between 373 and 393 K. After mixing, the saturated aqueous solution is expanded through a nozzle into the spray tower that operates at ambient pressure and a temperature that should be above the dew line of the binary CO2/H2O mixture. Figure 6.3 shows schematically a Tex,y diagram for such a binary system. Depending on the temperature in the spray tower and the water content, the mixture of CO2 and H2O can either consist of a single phase (vapor, i.e., T > T1) or two phases (vapor and liquid, i.e., T ¼ T2). This figure shows the dew point curve (full line), at which the first H2O droplet is formed. Operation conditions above this line lead to a single vapor phase, which can easily be removed from the spray tower. On the left side of the diagram is the bubble point curve (dashed line) at which the first gas bubble is formed in the liquid phase. However, in case of atmospheric pressure (¼ 0.1 MPa), the solubility of CO2 in H2O water is very low and the bubble point curve is almost identical with the ordinate. In the range between the two curves, a twophase vaporeliquid equilibrium exists. In addition, the determination of the optimal process temperature in the tower requires information about the thermal stability of the compound to be processed. If these data are available, PGSS drying can be used for processing both hydrophilic and heat-sensitive substances. The properties of the dry product, such as particle size, morphology, and residual moisture of the powder, can be adjusted by the processing parameters gaseliquid ratio, saturation temperature and pressure, as well as temperature inside the spray tower. Martin and Weidner [17] performed an extensive
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experimental and theoretical study on the micronization of PEG 6000 from an aqueous solution. The most important results of these investigations are that both residual moisture and particle size is decreased by an increase of the gaseliquid ratio. This is caused by an improved drying and/or faster cooling and higher dilution of the particulate phase (Section 6.2.1) whiles the morphology of the particles is mainly influenced by the residual moisture.
6.2.4 Depressurization of an Expanded Liquid Organic Solution The DELOS process, which was developed and patented by Ventosa et al. [19,20], is technically speaking a further modification of both PGSS and GAS. The SCF (e.g., sc-CO2) is dissolved in a liquid organic solution that contains the solute of interest and causes a volumetric expansion of the organic liquid (see also Section 5.1, Eqn (5.1)). Then, the saturated solution, which contains the SCF, is expanded from the high mixing pressure down to atmospheric pressure inside the expansion chamber. Thus, the driving force for the crystallization process is the fast and homogeneous temperature decrease caused by the evaporation of the CO2 out of the liquid phase, which causes the precipitation of submicron particles with a narrow particle distribution. However, it is important to consider that the DELOS process can only be used for substances for which the antisolvent effect of CO2 is small since otherwise the solute precipitates in the saturator and not in the expansion chamber. Thus, this process can be applied as long as the solution with the dissolved solute is completely miscible with the SCF. In opposition to the already discussed SCF-based particle formation processes (i.e., RESS, GAS, PGSS, and their various modifications), the SCF behaves in the DELOS process as co- and antisolvent for the solute which is dissolved in the initial organic solution. Such a behavior is depicted in Figure 6.4 for the solubility of naproxen in pure ethanol (x1 ¼ 0) and in CO2/ethanol mixtures at p ¼ 10 MPa and T ¼ 298.15 K. It is obvious that CO2 behaves as cosolvent for a CO2 molar fraction, x1, between 0.0 and 0.7 and as an antisolvent in the range from 0.7 to 1.0. Thus, above the “threshold value” of x1 > 0.7, precipitation of naproxen occurs. Therefore, in order to identify the best process conditions, it is of crucial importance that reliable vaporeliquid equilibria data of the ternary CO2/ organic solvent/solute mixture are available. The product propertiesdsuch as particle size, size distribution, and morphology of the obtained productdcan be adjusted by the processing parameters that are temperature decrease, flow rate through the nozzle, and CO2 concentration in the liquid solution during expansion from the high mixing pressure down to atmospheric pressure. Interim summary: While in the classical PGSS process, a binary gassaturated solution is expanded through a nozzle into a spray tower, all further developments of this process are characterized by processing at least
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FIGURE 6.4 Solubility of naproxen in pure ethanol and in CO2/ethanol mixtures at p ¼ 10 MPa and T ¼ 298.15 K. Full line represents ideal dilution behavior; experimental data are taken from Ref. [21].
three different substances. In the CPF process, both the SCF and the liquid solution are mixed prior to depressurization. During the expansion, a porous carrier is blown by means of an inert gas directly into the spray in the upper part of the spray tower and solid agglomerates are formed. In case of CPCSP, PGSS drying, and DELOS, the different substances that should be processed are mixed in two steps under a (high) operation pressure. First of all, a liquid solution which contains at least one valuable substance is formed. After that, sc-CO2 is dissolved in the binary mixture under preexpansion pressure, followed by the expansion of the ternary mixture into the spay tower. During the expansion down to atmospheric pressure, CO2 evaporates and small particles are formed.
6.3 CONDITIONS FOR SUCCESSFUL PARTICLE FORMATIONdTYPICAL RESULTS The PGSS process and its various modifications have been investigated for more than 20 years from different research groups. A very detailed and comprehensive summary of the systems investigated, e.g., Table 3 in Ref. [6], Tables 2 and 5 in Ref. [8], and Table 6 in Ref. [9], can be found in various review articles [6e9]. For the selection of the optimum process conditions for the PGSS, CPF, CPCSP, and PGSS drying processes, it is obvious that a high solubility of the
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SCF in the liquid melt, which often requires a high saturation pressure, is preferable. The high CO2eliquid ratio leads to a significant viscosity reduction, a faster cooling, and higher dilution of the particulate phase inside the spray tower and in smaller particles and a narrower size distribution. Thus, with the exception of the CPF process, information about the ternary phase behavior CO2ebinary liquid solution at preexpansion conditions is essential for the selection of the best operation conditions. Regarding to PGSS drying, Pham et al. [18] published a diagram in which different possible fields of operation are marked. With the help of the diagram, suitable parameters (preexpansion temperature, preexpansion pressure, and specific amount of CO2) can be selected in order to obtain powders with low residual solvent contents. For a complete removal of the water with the PGSS drying process, the operating point in the spray tower must be higher than the dew point, i.e., in a region in which a single gas phase exists. Thus, the knowledge of phase equilibrium data for the binary system CO2/H2O at the given operation pressure in the spray tower is needed since condensation of H2O leads to a remoistening of the dry powder. A further limitation might be either the melting temperature at atmospheric pressure and/or thermal stability of the product. In case of PEG 4000, the melting temperature is 330 K [5], thus the operating temperature must be below T2 ¼ 330 K (Figure 6.3). An important advantage of the DELOS process is the reduced CO2 consumption in comparison to the previous processes. According to Ventosa et al. [19], it operates at atmospheric pressure in the expansion chamber and a stirring system inside the (high pressure) mixing vessel is not crucial which simplifies the mechanical complexity. In case of the DELOS process, the SCF is acting as a co- and an antisolvent which enables process control by changing the initial supersaturation (Figure 6.4). However, this process parameter should be changed with caution since the product yield decreases with reduced supersaturation. From experimental investigations follows that the initial CO2 concentration in the liquid solution is the most important process parameter that controls the temperature decrease during depressurization. This can be explained by the influence of the required enthalpy of vaporization for evaporation of the CO2, which is directly proportional to the dissolved amount of CO2. Another important point is that, as shown by Sala et al. [20], DELOS can be used to produce polymorphs that cannot be obtained with other crystallization techniques. As an example, in case of the stearic acid, the polymorph E has been produced with DELOS while polymorph C was obtained with GAS. Interim summary: For all processes discussed above holds that both an increasing amount of CO2 in the liquid phase and a higher pressure drop during expansion lead to a lower product yield but smaller particles, caused by faster cooling due to the higher expansion rate (Section 3.1). Furthermore, the PGSS process offers a mechanism for controlling both macro- and microporosity via a single-step process. However, it should be considered that the
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particle size obtained from PGSS drying is similar to that obtained with the classical PGSS technique without H2O.
REFERENCES [1] E. Weidner, Z. Knez, Z. Novak, Process for Preparing Particles or Powders, International Patent WO 95/21688, 1995. [2] E. Weidner, R. Steiner, Z. Knez, Powder generation from polyethyleneglycol with compressible fluids, in: High Pressure Chemical Engineering, Elsevier, Amsterdam, 1996, p. 223. [3] E. Weidner, M. Petermann, Z. Knez, Multifunctional composites by high pressure spray processes, Curr. Opin. Solid State Mater. 7 (2003) 385e390. [4] http://www.vtp.ruhr-uni-bochum.de/pgss.html. [5] E. Weidner, V. Wiesmet, Z. Knez, M. Skerget, Phase equilibrium (solid-liquid-gas) in polyethyleneglycol-carbon dioxide systems, J. Supercrit. Fluids 10 (1997) 139e147. [6] J. Jung, M. Perrut, Particle design using supercritical fluids: literature and patent survey, J. Supercrit. Fluids 20 (2001) 179e219. [7] E. Weidner, High pressure micronization for food applications, J. Supercrit. Fluids 47 (2009) 556e565. [8] A.V.M. Nunes, C.M.M. Duarte, Dense CO2 as a solute, co-solute or co-solvent in particle formation processes: a review, Materials 4 (2011) 2017e2041. [9] D. Sanli, S.E. Bozbag, C. Erkey, Synthesis of nanostructured materials using supercritical CO2: part I. Physical transformations, J. Mater. Sci. 47 (2012) 2995e3025. [10] E. Weidner, R. Steiner, H. Dirscherl, B. Weinreich, Verfahren zur Herstellung eines pulverfo¨rmigen Produktes aus einem flu¨ssigen Stoff oder Stoffgemisch, European Patent, EP, October 6, 1997, p. 9705484. [11] M. Petermann, E. Weidner, S. Gru¨ner, B. Weinreich, CPF e concentrated powder form e a high pressure spray agglomeration technique, in: Proceedings of the Spray Drying ’01 and Related Processes, October 2001, pp. 8e10. Dortmund, Germany. [12] H. Lankes, Maximale Flu¨ssigkeitsaufnahmekapazita¨t von dispersen Tra¨gerstoffen beim Beladen und Tra¨nken (Ph.D. thesis), University of Munich, 2002. [13] E. Weidner, M. Petermann, K. Blatter, V. Rekowski, Manufacture of powder coatings by spraying of gas-enriched melts, Chem. Eng. Technol. 24 (2001) 529e533. [14] D. Meterc, M. Petermann, E. Weidner, Drying of aqueous green tea extracts using a supercritical fluid spray process, J. Supercrit. Fluids 45 (2008) 253e259. ´ . Martı´n, M.J. Cocero, Formulation of lavandin essential oil with [15] S. Varona, S. Kareth, A biopolymers by PGSS for application as biocide in ecological agriculture, J. Supercrit. Fluids 54 (2010) 369e377. ´ . Martı´n, H. Minh Pham, A. Kilzer, S. Kareth, E. Weidner, Micronization of polyethylene [16] A glycol by PGSS (particles from gas saturated solutions) e drying of aqueous solutions, Chem. Eng. Process. 49 (2010) 1259e1266. ´ . Martı´n, E. Weidner, PGSS-drying: mechanisms and modeling, J. Supercrit. Fluids 55 [17] A (2010) 271e281. [18] M. Pham, S. Pollak, M. Petermann, Micronisation of poly(ethylene oxide) solutions and separation of water by PGSS-Drying, J. Supercrit. Fluids 64 (2012) 19e24. [19] N. Ventosa, S. Sala, J. Veciana, DELOS process: a crystallization technique using compressed fluids, J. Supercrit. Fluids 26 (2003) 33e45.
96 Particle Formation with Supercritical Fluids [20] S. Sala, E. Elizondo, E. Moreno, T. Calvet, M.A. Cuevas-Duarte, N. Ventosa, J. Veciana, Kinetically driven crystallization of a pure polymorphic phase of stearic acid from CO2expanded solutions, Cryst. Growth Des. 10 (2010) 1226e1232. [21] M. Munto´, N. Ventosa, S. Sala, J. Veciana, Solubility behaviors of ibuprofen and naproxen drugs in liquid “CO2eorganic solvent” mixtures, J. Supercrit. Fluids 47 (2008) 147e153.
Formation of Organic Particles Using a Supercritical Fluid as Solute 6.1 PARTICLES FROM GAS SATURATED SOLUTIONS Another high-pressure particle formation technique is the particles from gassaturated solutions (PGSS) process, which eliminates solubility limitations and large amounts of gas usage. The PGSS process can operate in both a batch or a continuous mode. This method was developed in 1995 by Weidner et al. [1e3] and is based on the fact that the solubility of compressed gas (usually sc-CO2) in a liquid substance and/or high-molecular weight substance (e.g., polymer) is much higher than the solubility of these substances in SCFs. A schematic representation of the PGSS process is given in Figure 6.1. In this particle formation process, CO2 is fed into a high-pressure vessel and dissolved in a molten substance at high pressure, leading to a gas-saturated solution combined with a viscosity reduction. After intensive mixing in a, e.g., static mixer, the solution is rapidly expanded through a nozzle into a spray tower to a lower (usually ambient) pressure. Thereby the CO2 evaporates from the droplets, which induces a high supersaturation and therewith solidification and particle precipitation due to the large temperature decrease. Thereafter, the solid particles are separated from the gas by means of a filter and a cyclone. In general, adjusting the process parameters, such as SCF concentration in the molten liquid, preexpansion temperature and pressure, nozzle geometry, and temperature and pressure in the spray tower, can control the product properties. Similar to the RESS process (Chapter 4), the knowledge of the SLG line of the substance of interest is important for the selection of the best operation conditions since the SLG line determines if the melted substance will form solid or liquid particles in the spray tower. A typical peT diagram for a binary CO2/poly-ethylene glycol (PEG) system is depicted in the left part of Figure 6.2 while in the right diagram, the influence of pressure on the mass fraction of PEG in CO2 is shown for a certain temperature [5]. It is obvious that with increasing the CO2 pressure, the PEG 4000 melting temperature, with Particle Formation with Supercritical Fluids. http://dx.doi.org/10.1016/B978-0-444-59486-0.00006-1 Copyright © 2014 Elsevier B.V. All rights reserved.
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FIGURE 6.1 Schematic diagram of particle processing by the PGSS technique [4].
FIGURE 6.2 Phase diagrams for the binary CO2/PEG 4000 mixture; experimental data are taken from Ref. [5].
the exception of low pressures (<1 MPa), decreases from 330 K at ambient pressure to 315 K at 8.2 MPa. In opposite thereto, the temperature is nearly constant for pressures between 8.2 and 20 MPa while at higher pressures, the SLG line increases again. Furthermore, at constant pressure, the CO2 concentration decreases with increasing temperature, and increases with increasing pressure for constant temperature. It is shown in the right diagram of Figure 6.2 for T ¼ 333 K that increasing the pressure from 0.4 to 28 MPa increases the CO2 mass fraction from about 0.07 to 0.28 [5].
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Typically the PGSS process operates at pressures in the range from 3 to 25 MPa and a CO2 consumption of 0.1e2 kg gas per kg solute [4]. Furthermore, the PGSS process allows forming particles from different kind of substances that need not to be soluble in sc-CO2, especially such polymers which are able to absorb large amounts (up to 40 wt%) of CO2. This process can also be applied for a mixture of active ingredient(s) and polymer(s) to produce composite particles. In addition, it is worthy to notice that in contrast to the common antisolvent techniques (Chapter 5), no organic solvent is required in the PGSS process. Compared to RESS, PGSS requires less-dense gas and a lower pressure which can lead to some economic advantages. However, both RESS and PGSS enable the production of a solvent-free powder.
6.2 MODIFICATION OF THE PGSS PROCESS While in the classical PGSS process a binary gas-saturated solution is expanded through a nozzle into a spray tower, all further developments of this process are characterized by processing at least three different substances. These basically identical processes are named as concentrated powder form (CPF), continuous powder coating spraying process (CPCSP), PGSS drying of aqueous solution (PGSS drying), and depressurization of an expanded liquid organic solution (DELOS). As described below, all these modifications are characterized by dissolution in the SCF in a premixed binary liquid mixture prior to the expansion of the ternary solution [6e9].
6.2.1 Concentrated Powder Form As a further development of the PGSS process, the CPF process has been proposed by Weidner et al. [10,11] in 1997. This process allows the generation of powders, which contain a very high content of liquids. Similar to the PGSS process, a dense gas is dissolved in a liquid substance and, after intensive mixing at high pressure, depressurized through a nozzle down to low pressure. Opposite to the PGSS method, a spray of fine droplets is formed during the expansion step of the gas-saturated liquid. At the same time and by means of an inert gas (e.g., N2), a powdered carrier compound is blown into the spray tower. Due to the expanding gas and the resultant high turbulent flow, both the droplets and the solid carrier are intensively mixed and solid agglomerates are formed. In case of a huge (i.e., high and wide) spray tower, a free-flowing powder that can contain up to 90 wt% (or more) of the liquid is formed [7]. The characteristics of the agglomerates are strongly influenced by the chemical and physical properties of the powdered carrier and the liquid. A detailed theoretical and experimental study shows that the bulk density of the carrier material is a suitable parameter to correlate the liquid uptake of the carrier [12]. For example, experiments show that silica with a bulk density of 50 g/dm3 are able to bind more than 90% of the liquid while a bulk density of
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200 g/dm3 leads to only 60 wt%. The reason therefore is mainly due to the much higher specific surface area of the silica with the lower bulk density. At this point, it should be considered that in opposition to the conventional PGSS process, particle precipitation does never occur. Depending on the properties of the carrier used, the highly dispersed agglomerates are formed either by penetration of the liquid into the porous carrier material or by simple agglomeration of the wetted less porous material.
6.2.2 Continuous Powder Coating Spraying Process Weidner et al. proposed a very interesting PGSS-based micronization process as an alternative technique for the manufacture of powder coatings [13]. Conventional coating techniques often require high temperatures and long residences times which may cause an unrequested decomposition that would destroy the product. The so-called CPCSP enables the processing of both conventional powder coating and (fast) reacting systems. In the CPCSP, each components of a powder coating mixture is melted in separate high-pressure vessels and high-pressure pumps fed both streams to a static mixer and are homogenized with dense CO2. As a consequence of the dissolved CO2, the mixture’s melting point is decreased which enables faster homogenization of the solution at lower temperatures. Now, similar to the other PGSS-based processes, the solution is expanded through a nozzle into the spray tower. Thereby fine droplets are formed which are cooled by the expanding gas. After crossing the solidification point of the liquid mixture (¼ SLG line, see left diagram of Figure 6.2), solid particles are formed. These particles can be separated from the gas by means of a cyclone and a filter while an exhauster removes the gas out of the spray tower. The product properties, mainly morphology of the powder, particle size, and size distribution, can be adjusted by the processing parameters such as saturation temperature and pressure. Experimental results show that lower saturation temperatures promote smaller particles with a narrower size distribution than higher temperatures. Increasing the saturation pressure results in smaller particles and a narrower size distribution which is mainly caused by the higher CO2 amount in the liquid solution (see right diagram of Figure 6.2) and hence higher dilution of the particulate phase in combination with faster cooling (Section 3.1).
6.2.3 PGSS Drying of Aqueous Solution Besides the applications described above, the so-called PGSS drying of aqueous solutions process can also be used for drying aqueous compounds (e.g., natural extracts such as green tea extracts) [14e18]. The process offers, compared to other drying processes such as spray-drying, some real advantages. It allows processing under gentle operation conditions which enables
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FIGURE 6.3 Schematic Tex,y diagram of a binary mixture. Depicted are the dew point curve (full line) and the bubble point curve (dashed line). Note that in case of the CO2eH2O mixture, T1 is equal to 373.15 K for p ¼ 0.1 MPa.
drying with reduced thermal degradation or contamination of the product. Furthermore, the process is carried out in a closed system under an inert gas (usually CO2) atmosphere. In a typical experiment, a static mixer is used to dissolve CO2 in an aqueous solution at pressures in the range from 10 to 15 MPa and temperatures between 373 and 393 K. After mixing, the saturated aqueous solution is expanded through a nozzle into the spray tower that operates at ambient pressure and a temperature that should be above the dew line of the binary CO2/H2O mixture. Figure 6.3 shows schematically a Tex,y diagram for such a binary system. Depending on the temperature in the spray tower and the water content, the mixture of CO2 and H2O can either consist of a single phase (vapor, i.e., T > T1) or two phases (vapor and liquid, i.e., T ¼ T2). This figure shows the dew point curve (full line), at which the first H2O droplet is formed. Operation conditions above this line lead to a single vapor phase, which can easily be removed from the spray tower. On the left side of the diagram is the bubble point curve (dashed line) at which the first gas bubble is formed in the liquid phase. However, in case of atmospheric pressure (¼ 0.1 MPa), the solubility of CO2 in H2O water is very low and the bubble point curve is almost identical with the ordinate. In the range between the two curves, a twophase vaporeliquid equilibrium exists. In addition, the determination of the optimal process temperature in the tower requires information about the thermal stability of the compound to be processed. If these data are available, PGSS drying can be used for processing both hydrophilic and heat-sensitive substances. The properties of the dry product, such as particle size, morphology, and residual moisture of the powder, can be adjusted by the processing parameters gaseliquid ratio, saturation temperature and pressure, as well as temperature inside the spray tower. Martin and Weidner [17] performed an extensive
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experimental and theoretical study on the micronization of PEG 6000 from an aqueous solution. The most important results of these investigations are that both residual moisture and particle size is decreased by an increase of the gaseliquid ratio. This is caused by an improved drying and/or faster cooling and higher dilution of the particulate phase (Section 6.2.1) whiles the morphology of the particles is mainly influenced by the residual moisture.
6.2.4 Depressurization of an Expanded Liquid Organic Solution The DELOS process, which was developed and patented by Ventosa et al. [19,20], is technically speaking a further modification of both PGSS and GAS. The SCF (e.g., sc-CO2) is dissolved in a liquid organic solution that contains the solute of interest and causes a volumetric expansion of the organic liquid (see also Section 5.1, Eqn (5.1)). Then, the saturated solution, which contains the SCF, is expanded from the high mixing pressure down to atmospheric pressure inside the expansion chamber. Thus, the driving force for the crystallization process is the fast and homogeneous temperature decrease caused by the evaporation of the CO2 out of the liquid phase, which causes the precipitation of submicron particles with a narrow particle distribution. However, it is important to consider that the DELOS process can only be used for substances for which the antisolvent effect of CO2 is small since otherwise the solute precipitates in the saturator and not in the expansion chamber. Thus, this process can be applied as long as the solution with the dissolved solute is completely miscible with the SCF. In opposition to the already discussed SCF-based particle formation processes (i.e., RESS, GAS, PGSS, and their various modifications), the SCF behaves in the DELOS process as co- and antisolvent for the solute which is dissolved in the initial organic solution. Such a behavior is depicted in Figure 6.4 for the solubility of naproxen in pure ethanol (x1 ¼ 0) and in CO2/ethanol mixtures at p ¼ 10 MPa and T ¼ 298.15 K. It is obvious that CO2 behaves as cosolvent for a CO2 molar fraction, x1, between 0.0 and 0.7 and as an antisolvent in the range from 0.7 to 1.0. Thus, above the “threshold value” of x1 > 0.7, precipitation of naproxen occurs. Therefore, in order to identify the best process conditions, it is of crucial importance that reliable vaporeliquid equilibria data of the ternary CO2/ organic solvent/solute mixture are available. The product propertiesdsuch as particle size, size distribution, and morphology of the obtained productdcan be adjusted by the processing parameters that are temperature decrease, flow rate through the nozzle, and CO2 concentration in the liquid solution during expansion from the high mixing pressure down to atmospheric pressure. Interim summary: While in the classical PGSS process, a binary gassaturated solution is expanded through a nozzle into a spray tower, all further developments of this process are characterized by processing at least
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FIGURE 6.4 Solubility of naproxen in pure ethanol and in CO2/ethanol mixtures at p ¼ 10 MPa and T ¼ 298.15 K. Full line represents ideal dilution behavior; experimental data are taken from Ref. [21].
three different substances. In the CPF process, both the SCF and the liquid solution are mixed prior to depressurization. During the expansion, a porous carrier is blown by means of an inert gas directly into the spray in the upper part of the spray tower and solid agglomerates are formed. In case of CPCSP, PGSS drying, and DELOS, the different substances that should be processed are mixed in two steps under a (high) operation pressure. First of all, a liquid solution which contains at least one valuable substance is formed. After that, sc-CO2 is dissolved in the binary mixture under preexpansion pressure, followed by the expansion of the ternary mixture into the spay tower. During the expansion down to atmospheric pressure, CO2 evaporates and small particles are formed.
6.3 CONDITIONS FOR SUCCESSFUL PARTICLE FORMATIONdTYPICAL RESULTS The PGSS process and its various modifications have been investigated for more than 20 years from different research groups. A very detailed and comprehensive summary of the systems investigated, e.g., Table 3 in Ref. [6], Tables 2 and 5 in Ref. [8], and Table 6 in Ref. [9], can be found in various review articles [6e9]. For the selection of the optimum process conditions for the PGSS, CPF, CPCSP, and PGSS drying processes, it is obvious that a high solubility of the
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SCF in the liquid melt, which often requires a high saturation pressure, is preferable. The high CO2eliquid ratio leads to a significant viscosity reduction, a faster cooling, and higher dilution of the particulate phase inside the spray tower and in smaller particles and a narrower size distribution. Thus, with the exception of the CPF process, information about the ternary phase behavior CO2ebinary liquid solution at preexpansion conditions is essential for the selection of the best operation conditions. Regarding to PGSS drying, Pham et al. [18] published a diagram in which different possible fields of operation are marked. With the help of the diagram, suitable parameters (preexpansion temperature, preexpansion pressure, and specific amount of CO2) can be selected in order to obtain powders with low residual solvent contents. For a complete removal of the water with the PGSS drying process, the operating point in the spray tower must be higher than the dew point, i.e., in a region in which a single gas phase exists. Thus, the knowledge of phase equilibrium data for the binary system CO2/H2O at the given operation pressure in the spray tower is needed since condensation of H2O leads to a remoistening of the dry powder. A further limitation might be either the melting temperature at atmospheric pressure and/or thermal stability of the product. In case of PEG 4000, the melting temperature is 330 K [5], thus the operating temperature must be below T2 ¼ 330 K (Figure 6.3). An important advantage of the DELOS process is the reduced CO2 consumption in comparison to the previous processes. According to Ventosa et al. [19], it operates at atmospheric pressure in the expansion chamber and a stirring system inside the (high pressure) mixing vessel is not crucial which simplifies the mechanical complexity. In case of the DELOS process, the SCF is acting as a co- and an antisolvent which enables process control by changing the initial supersaturation (Figure 6.4). However, this process parameter should be changed with caution since the product yield decreases with reduced supersaturation. From experimental investigations follows that the initial CO2 concentration in the liquid solution is the most important process parameter that controls the temperature decrease during depressurization. This can be explained by the influence of the required enthalpy of vaporization for evaporation of the CO2, which is directly proportional to the dissolved amount of CO2. Another important point is that, as shown by Sala et al. [20], DELOS can be used to produce polymorphs that cannot be obtained with other crystallization techniques. As an example, in case of the stearic acid, the polymorph E has been produced with DELOS while polymorph C was obtained with GAS. Interim summary: For all processes discussed above holds that both an increasing amount of CO2 in the liquid phase and a higher pressure drop during expansion lead to a lower product yield but smaller particles, caused by faster cooling due to the higher expansion rate (Section 3.1). Furthermore, the PGSS process offers a mechanism for controlling both macro- and microporosity via a single-step process. However, it should be considered that the
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particle size obtained from PGSS drying is similar to that obtained with the classical PGSS technique without H2O.
REFERENCES [1] E. Weidner, Z. Knez, Z. Novak, Process for Preparing Particles or Powders, International Patent WO 95/21688, 1995. [2] E. Weidner, R. Steiner, Z. Knez, Powder generation from polyethyleneglycol with compressible fluids, in: High Pressure Chemical Engineering, Elsevier, Amsterdam, 1996, p. 223. [3] E. Weidner, M. Petermann, Z. Knez, Multifunctional composites by high pressure spray processes, Curr. Opin. Solid State Mater. 7 (2003) 385e390. [4] http://www.vtp.ruhr-uni-bochum.de/pgss.html. [5] E. Weidner, V. Wiesmet, Z. Knez, M. Skerget, Phase equilibrium (solid-liquid-gas) in polyethyleneglycol-carbon dioxide systems, J. Supercrit. Fluids 10 (1997) 139e147. [6] J. Jung, M. Perrut, Particle design using supercritical fluids: literature and patent survey, J. Supercrit. Fluids 20 (2001) 179e219. [7] E. Weidner, High pressure micronization for food applications, J. Supercrit. Fluids 47 (2009) 556e565. [8] A.V.M. Nunes, C.M.M. Duarte, Dense CO2 as a solute, co-solute or co-solvent in particle formation processes: a review, Materials 4 (2011) 2017e2041. [9] D. Sanli, S.E. Bozbag, C. Erkey, Synthesis of nanostructured materials using supercritical CO2: part I. Physical transformations, J. Mater. Sci. 47 (2012) 2995e3025. [10] E. Weidner, R. Steiner, H. Dirscherl, B. Weinreich, Verfahren zur Herstellung eines pulverfo¨rmigen Produktes aus einem flu¨ssigen Stoff oder Stoffgemisch, European Patent, EP, October 6, 1997, p. 9705484. [11] M. Petermann, E. Weidner, S. Gru¨ner, B. Weinreich, CPF e concentrated powder form e a high pressure spray agglomeration technique, in: Proceedings of the Spray Drying ’01 and Related Processes, October 2001, pp. 8e10. Dortmund, Germany. [12] H. Lankes, Maximale Flu¨ssigkeitsaufnahmekapazita¨t von dispersen Tra¨gerstoffen beim Beladen und Tra¨nken (Ph.D. thesis), University of Munich, 2002. [13] E. Weidner, M. Petermann, K. Blatter, V. Rekowski, Manufacture of powder coatings by spraying of gas-enriched melts, Chem. Eng. Technol. 24 (2001) 529e533. [14] D. Meterc, M. Petermann, E. Weidner, Drying of aqueous green tea extracts using a supercritical fluid spray process, J. Supercrit. Fluids 45 (2008) 253e259. ´ . Martı´n, M.J. Cocero, Formulation of lavandin essential oil with [15] S. Varona, S. Kareth, A biopolymers by PGSS for application as biocide in ecological agriculture, J. Supercrit. Fluids 54 (2010) 369e377. ´ . Martı´n, H. Minh Pham, A. Kilzer, S. Kareth, E. Weidner, Micronization of polyethylene [16] A glycol by PGSS (particles from gas saturated solutions) e drying of aqueous solutions, Chem. Eng. Process. 49 (2010) 1259e1266. ´ . Martı´n, E. Weidner, PGSS-drying: mechanisms and modeling, J. Supercrit. Fluids 55 [17] A (2010) 271e281. [18] M. Pham, S. Pollak, M. Petermann, Micronisation of poly(ethylene oxide) solutions and separation of water by PGSS-Drying, J. Supercrit. Fluids 64 (2012) 19e24. [19] N. Ventosa, S. Sala, J. Veciana, DELOS process: a crystallization technique using compressed fluids, J. Supercrit. Fluids 26 (2003) 33e45.
96 Particle Formation with Supercritical Fluids [20] S. Sala, E. Elizondo, E. Moreno, T. Calvet, M.A. Cuevas-Duarte, N. Ventosa, J. Veciana, Kinetically driven crystallization of a pure polymorphic phase of stearic acid from CO2expanded solutions, Cryst. Growth Des. 10 (2010) 1226e1232. [21] M. Munto´, N. Ventosa, S. Sala, J. Veciana, Solubility behaviors of ibuprofen and naproxen drugs in liquid “CO2eorganic solvent” mixtures, J. Supercrit. Fluids 47 (2008) 147e153.