The Formation of Fluorinated Tetraphenylporphyrin Nanoparticles via

Oct 5, 2005 - Amporn Sane† and Mark C. Thies*. Center for AdVanced Engineering Fibers and Films, Department of Chemical Engineering, Clemson ...
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J. Phys. Chem. B 2005, 109, 19688-19695

The Formation of Fluorinated Tetraphenylporphyrin Nanoparticles via Rapid Expansion Processes: RESS vs RESOLV Amporn Sane† and Mark C. Thies* Center for AdVanced Engineering Fibers and Films, Department of Chemical Engineering, Clemson UniVersity, Clemson, South Carolina 29634-0909 ReceiVed: March 24, 2005

Organic nanoparticles of a fluorinated tetraphenylporphyrin (TBTPP) were produced by rapid expansion of supercritical CO2 solutions into both air (RESS) and an aqueous receiving solution containing a stabilizing agent (RESOLV). The effect of processing conditions on both particle size and form was investigated. The size of the porphyrin nanoparticles produced via RESS increased in a well-behaved manner from 40 to 80 nm as the preexpansion temperature increased from 40 to 100 °C, independent of porphyrin concentration, degree of saturation, and preexpansion pressure. RESOLV of TBTPP + CO2 solutions was investigated both for minimizing particle growth in the free jet and for the prevention of particle agglomeration. Anionic, nonionic, and polymeric stabilizing agents for the aqueous receiving solution were considered. Expansion into a 0.05 wt % SDS solution produced nanorods 50-100 nm in diameter with an aspect ratio of 3-5. RESOLV in a 0.025 wt % Pluronic F68 solution produced well-dispersed, individual, spherical nanoparticles averaging 23 ( 10 to 32 ( 10 nm in diameter, independent of the rapid expansion processing conditions selected. Furthermore, the resulting nanoparticle suspensions were stable, with particle sizes remaining unchanged after several months. However, some particle agglomeration occurred at higher (i.e., 1 wt % TBTPP in CO2) concentrations. Contact-angle measurements on solid TBTPP compacts with the tested receiving solutions indicate that a moderate wetting agent such as Pluronic F68 is most effective for preserving the size and form of the porphyrin nanoparticles produced by RESOLV. Finally, the fact that nanoparticles are produced from RESS of TBTPP, in contrast with other organics for which microparticles are produced, can be explained in terms of the high melting point of TBTPP (388 °C), which results in a solid-state diffusion coefficient of TBTPP low enough so that particle coalescence is significantly reduced in the free jet.

Introduction Conventional techniques for producing organic and polymeric nanoparticles (i.e., particles of 100 nm or less) have several limitations, including generating broad particle size distributions, using organic solvents that must be removed from the final products, and requiring large amounts of surfactants to reach particle sizes below 100 nm.1-3 Rapid expansion of supercritical solutions (RESS) technology is recognized as a well-established technique for producing micrometer-sized particles from organics and polymers.4-11 However, recently we have discovered that RESS can also be used to consistently produce nanoparticles (58 ( 16 nm) of a fluorinated tetraphenylporphyrin, 5,10,15,20-tetrakis(3,5-bis(trifluoromethyl)phenyl)porphyrin (TBTPP), from solutions in CO2.12 To our knowledge, no other group has yet to report the use of RESS for producing organic nanoparticles. Still unanswered is the question as to why RESS can be used to produce nanoparticles from TBTPP, but not from the myriad of other compounds that have been investigated. For organic particles produced via RESS, there is lack of fundamental knowledge on how the physical and chemical properties of the solute affect the particle growth. RESS modeling work from * Corresponding author. Telephone: +1-864-656-5424. Fax: +1-864656-0784. E-mail: [email protected]. † Current address: Kasetsart University, Agro-Industry; Department of Physico-Chemical Processing Technology, 50 Paholyothin Rd., Lad Yao, Chatu Chak, Bangkok 10900, Thailand

several groups13-15 all predict that only nanoparticles are formed up to the Mach disk, but that the particles grow by coagulation into submicrometer and micrometer sizes downstream of the Mach disk in the transonic and subsonic free-jet regions. A modification of conventional RESS is the so-called RESOLV (rapid expansion of supercritical solutions into liquid solVents) process,16,17 in which the supercritical solution is directly expanded into a liquid receiving solution (typically aqueous in nature) that may or may not contain a stabilizing agent. Organic particles produced via RESOLV have been found to be smaller than those obtained by RESS. Submicrometersized particles (40-920 nm) were obtained from cyclosporin,18,19 particles with a bimodal size distribution were obtained from β-sitosterol (5-50 and 120-200 nm)10 and phytosterol (1255 and 60-540 nm),20 and nanoparticles (25-60 nm) were recently produced from ibuprofen, naproxen, and a fluorinated acrylate polymer.16,17 However, agglomeration of organic and polymeric nanoparticles often occurs in the receiving solutions.16,17 Moreover, only limited work has been done toward understanding the effect of process variables on the size, form, and dispersibility of the particles created by RESOLV. Thus, it remains a challenge to produce well-dispersed nanoparticles by RESOLV. The formation of dispersions from a collection of particles (i.e., powders) generally involves three stages: (1) wetting of the powder, (2) breaking up of agglomerates and aggregates to colloidal size, and (3) stabilization of the dispersion itself.21-23

10.1021/jp0581072 CCC: $30.25 © 2005 American Chemical Society Published on Web 10/05/2005

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In principle, RESOLV should facilitate the dispersion process. Classical nucleation theory predicts that during rapid expansion nanoparticles are initially formed; by expanding into a receiving solution, the subsequent growth processes of condensation and coagulation that occur in the free jet should be suppressed. Thus, the need for the mechanical breakup of particles should be obviated, and the wetting and stabilization processes required to create dispersions should occur more at the level of individual particles. As originally described by Osterhof and Bartell,24 the wetting of solid particles involves three sequential processes: adhesion, immersion, and spreading. Each of these is defined by the changes in interfacial free energy that occur according to the interfaces that are created or destroyed. Spreading wetting is the least spontaneous of the three wetting processes, with the driving force (i.e., the decrease in the interfacial free energy per unit surface area) being less than that of immersion and adhesion by γLV and 2γLV, respectively, where γLV is the surface tension of the liquid. (Interfacial tension is defined as the interfacial free energy per unit surface area, and the term surface tension can be used when one of the interfaces is a gas or a vapor.) Because spreading wetting has the smallest driving force and is the last step in the submersion of particles into liquid, it is typically used as a measure of complete wetting of solid particles.22,25 The driving force behind spreading wetting is known as the spreading coefficient (SL/S), which is defined as

SL/S ) γSV - γSL - γLV

(1)

where γSV, γSL, and γLV are, respectively, the interfacial tensions of the solid-gas, solid-liquid, and liquid-gas interfaces. If SL/S is positive, complete wetting can occur spontaneously; if SL/S is negative, the liquid will not wet spontaneously over the particle surface. For a solid substrate, the values of γSV and γSL cannot be directly measured; thus, SL/S must be evaluated by indirect means. The equilibrium contact angle θ is the key characteristic property of the solid-liquid-vapor system that enables us to obtain SL/S and is defined by Young’s equation:22

γSV - γSL ) γLV cos θ

(2)

Substituting eq 2 into 1 yields

SL/S ) γLV(cos θ - 1)

(3)

On the basis of the contact angle concept, the maximum value of cos θ is 1 at θ ) 0°. (Even though it is impossible to measure a contact angle of less than 0°, eq 1 shows that a greater driving force in a wetting process can be obtained.) Thus, the maximum value of SL/S is 0, which indicates complete wetting. Unlike spreading wetting, immersion and adhesion wetting occur spontaneously when θ e 90° and θ e 180°, respectively.22 During expansion of the supercritical solution into the receiving liquid, the solute precipitates as a solid, and the CO2 expands to form a low-pressure gas surrounded by the liquid receiving solution. As the solid and liquid phases come into contact, the solid-gas interface is replaced by a solid-liquid interface. Clearly, then, this phenomenon is a wetting process. By modification of the wetting characteristics of the receiving solution (e.g., by the addition of stabilizing agents), the dispersibility of the nanoparticles formed in RESOLV can be affected, and perhaps even controlled. In addition to the effective wetting of the particles, the stability of the dispersion formed should also be considered. Dispersion stability can depend on the particle size, the particle size distribution, and on the

Figure 1. Schematic of the rapid expansion experimental apparatus.

Figure 2. Schematic of the nozzle assembly used for rapid expansion experiments.

solubility of the solute in the dispersion medium (i.e., the receiving solution).23 Surfactants added to the aqueous dispersions to enhance wetting can dissolve organic particles and create undesirable effects, including (1) Ostwald ripening, in which larger particles grow at the expense of smaller ones due to the higher solubility of the smaller particles,26 and (2) changes in particle shape caused by the micellar structure that forms with the surfactant above the critical micelle concentration (cmc).22 In this work, we report on (1) the use of RESS and RESOLV to produce fluorinated tetraphenylporphyrin nanoparticles in the form of dry powders and suspensions, respectively, (2) the effect of selected stabilizing agents on the dispersibility of TBTPP nanoparticles produced by RESOLV, and (3) the effect of RESS and RESOLV processing conditions on particle size and morphology. Experimental Section Materials. TBTPP was synthesized by a modified Rothemund reaction, the condensation reaction between 3,5-bis(trifluoromethyl)benzaldehyde and pyrrole with an acidic catalyst. Details of the synthesis, which was carried out by Sun and co-workers, are described elsewhere.27 Water (HPLC grade) was purchased from VWR Scientific Products. Poly(vinylpyrrolidone) (PVP; MW ) 40 000) and sodium dodecyl sulfate (SDS; cmc ) 0.24 wt %) were purchased from Aldrich. Pluronic F68 (MW ) 8400; cmc ) 1.18 wt %) and Silwet L77 (cmc ) 0.007 wt %) were supplied by BASF and GE Silicones-Osi Specialties, respectively. CO2 (Coleman Instrument Grade, 99.99%) was obtained from National Welders Supply. RESS and RESOLV. Rapid expansion experiments with CO2 + TBTPP solutions were carried out using the apparatus shown in Figure 1. Figure 2 is a schematic of the nozzle that was specifically designed for accurate measurement and control of the true preexpansion temperature (Tpre). Tpre was measured with an ultrathin 0.5 mm o.d., type K thermocouple (Thermocoax) located inside the preexpansion tubing about 1 mm upstream of the nozzle. The thermocouple was axially centered

19690 J. Phys. Chem. B, Vol. 109, No. 42, 2005 inside the tubing with a gland. A 1 mm o.d. cable heater (Thermocoax 1NcI10) was inserted into the grooves in the preexpansion tubing in order to provide heat to the fluid during expansion across the nozzle. The nozzle pinhole (50 µm dia., L/D ) 4) was manufactured using the microelectrical discharge machining technique (Optimation), creating a pinhole that is round, calibrated, and free from edge distortion. For a typical experiment, the variable-volume equilibrium cell (capacity ≈45 mL) was loaded with 0.02-0.20 ( 0.0005 g of TBTPP solid. The cell was then sealed, purged to remove all air, and charged with 20 ( 0.05 g of CO2 using the syringe pump (Isco 500HP). Before the mixture in the cell was heated to 40 °C in the isothermal bath, valve V2 was opened (while valves V1, V3, and V4 were closed), and the syringe pump was used to compress the mixture to the desired preexpansion pressure (as measured by pressure transducer P). The mixture in the cell was then stirred for 2 h using a magnetic stirrer to obtain a homogeneous solution. Next, valve V2 was closed in order to isolate the cell from the rest of system. Valve V3 was then opened, allowing pure CO2 to flow from the syringe pump (being operated in the constant-pressure mode) to the six-port switching valve (Valco Instruments 6C6UWEY) and then to expand across the nozzle, bypassing the equilibrium cell. The fluid in the tubing leading to the nozzle and nozzle assembly was heated to the desired preexpansion temperature using two additional cable heaters (Thermocoax 1NcI10). During the flow of pure CO2, the preexpansion temperature and pressure (Tpre, Ppre) were monitored upstream of the nozzle, see Figure 1. After steady-state conditions (as indicated by constant Tpre and Ppre) were obtained, valve V4 was opened and the switching valve was switched to the position shown in Figure 1 to divert the flow of pure CO2 to the working fluid side of the equilibrium cell, indirectly pushing the supercritical (SC) CO2 + TBTPP solution out of the cell by means of the movable piston. For RESS, the solution was subsequently expanded through the nozzle into an unheated, ambient-pressure 1.5-L chamber made from Pyrex conical end glass process pipe (10.2 cm i.d. × 11.5 cm o.d.). The minimum temperature attained in the chamber due to the cooling effect of CO2 expansion depended on Tpre and ranged from ∼2 to 20 °C. For RESOLV, 10 mL of SC solution was expanded into 50 mL of receiving solution by submerging the nozzle ∼2 cm below the liquid surface to rapidly create contact between the expanding solution, the particles being formed, and the receiving liquid. The tubing leading to the nozzle and nozzle assembly was insulated with a Teflon sleeve to minimize heat transfer from the heating cable to the receiving solution. The pH of the receiving solution before and after expansion was measured using a pH meter (Corning 430). Samples from both RESS and RESOLV experiments were characterized using field emission scanning electron microscopy (FESEM, Hitachi S4700). Samples from RESS were collected onto SEM stages located on the sampling device at 4 and 14 cm from the nozzle exit. For samples from RESOLV, one drop of the suspension was deposited onto a carbon-coated copper microgrid and dried at a pressure of 10 Torr at ambient temperature overnight. The average particle size and particle size distribution (PSD) were statistically determined from FESEM images using image analysis (Image-Pro Plus Version 4.0). Contact-Angle Measurement. Contact angles (θ) between compressed disks of TBTPP and receiving solutions were measured using the drop shape analysis system (Kru¨ss G10/ DSA10). TBTPP powder (0.16 g) was compacted in a die assembly (1.3 cm dia.) at a pressure of 690 bar using a Carver

Sane and Thies

Figure 3. Schematic of a liquid droplet on a TBTPP compact and the resulting contact angle (θ).

TABLE 1: Experimental Conditions and Sizes of TBTPP Nanoparticles Produced by RESS and RESOLV TBTPP [wt %]

Tpre [°C]

Ppre [bar]

S

RESS dp ( σ [nm]

RESOLVb dhp ( σ [nm]

0.1 0.1 1.0 0.1 0.1 1.0 0.1 0.1 1.0

40 40 40 70 70 70 100 100 100

128 273 287 187 280 288 228 298 303

0.9 0.1 0.9 0.9 0.1 0.9 0.9 0.1 0.9

45 ( 14, 30 ( 5a 42 ( 9, 30 ( 5 45 ( 12 61 ( 19 59 ( 17 60 ( 18, 54 ( 9 88 ( 16 86 ( 23, 82 ( 21 76 ( 18

29 ( 8, 27 ( 9 30 ( 8 26 ( 6 27 ( 9, 23 ( 10 29 ( 10 24 ( 6 26 ( 10 31 ( 10, 32 ( 10

a Duplicate run. b RESOLV experiments were with 0.025 wt % Pluronic F68 solution.

Press (Carver Press C).28 A drop of test liquid (receiving solution) was placed onto the powder compact (Figure 3), which had been saturated with the receiving solution by storing in a 95% relative humidity chamber at ambient temperature for 1 week in order to prevent the drop from penetrating the compact. The contact angle between the TBTPP surface and the receiving solution was measured within 1 s after deposition of the liquid droplet on the surface to avoid the effect of liquid penetrating into the solid.29 For each solution, measurements were repeated at least five times on two different TBTPP compacts. The reproducibility of contact angle values was generally better than 4°. For a given solution of known surface tension (γLV), contact angles were then used to calculate spreading coefficients using eq 3. Results and Discussion Before performing RESS and RESOLV experiments, the solubility of TBTPP in SC CO2 had been previously determined using a semicontinuous flow method.27 Solubility isotherms at 40, 70, and 100 °C were measured at pressures ranging from 103 to 304 bar. Because of the presence of the trifluoromethyl groups, TBTPP exhibits a relatively high solubility in SC CO2 (i.e., ∼1.5 wt % at 300 bar), approximately 2 orders of magnitude higher than nonfluorinated porphyrins. Effect of RESS Variables. RESS process variables selected for this investigation were the degree of saturation, concentration, and preexpansion temperature and pressure, as researchers have generally found that these variables can affect the size and morphology of RESS products4-10 (however, conflicting results are also not uncommon). The degree of saturation, S, is defined as the ratio of the actual solute concentration (C) (which is known from the cell charge) to the equilibrium concentration at preexpansion conditions (Tpre, Ppre). The average size (dhp) and standard deviation (σ) of TBTPP primary (individual) particles obtained from RESS at different processing conditions are shown in Table 1. At a preexpansion temperature of 40 °C, average particle sizes of ∼40 nm were reproducibly obtained, independent of C, Ppre, and S. Only Tpre was found to affect particle size, as increases in preexpansion temperature to 70

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Figure 5. FESEM micrograph of nanoparticles obtained from RESOLV into water of a 0.1 wt % TBTPP solution in CO2 with S ) 0.1, Tpre ) 40 °C, Ppre ) 273 bar.

Figure 6. Chemical structures of selected stabilizing agents.

Figure 4. FESEM micrographs of nanoparticles obtained from RESS of a TBTPP solution in CO2 with S ) 0.9: (a) 0.1 wt %, Tpre ) 40 °C, Ppre ) 128 bar; (b) 1.0 wt %, Tpre ) 70 °C, Ppre ) 288 bar; (c) 1.0 wt %, Tpre ) 100 °C, Ppre ) 303 bar.

and 100 °C increased the average particle size to ∼60 and ∼80 nm, respectively (see Table 1 and Figure 4).12 These nanoparticles were loosely agglomerated together because we were able to disperse them as individual particles in an aqueous solution containing 0.025 wt % Pluronic F68 after sonication for 1 min. No difference in particle size was observed whether the samples were collected either 4 or 14 cm downstream of the nozzle. Experiments were rerun several times to ensure reproducibility, and essentially identical results were obtained in all cases. Similar trends of increasing particle size with increasing Tpre were previously reported for the precipitation of naphthalene,4,7 salicylic acid,5 and benzoic acid10 from SC CO2 solutions; however, those particles were much larger (i.e., typically micrometer-sized) than our TBTPP nanoparticles. These results suggest that the size of particles produced by RESS depends on both the processing conditions and on the material properties of the solute. The increase in particle size that occurs with Tpre during RESS is consistent with classical nucleation theory, as a higher Tpre would give a higher temperature and vapor pressure in the downstream expansion jet and thus a lower degree of supersaturation for a given concentration, resulting in lower nucleation rates and larger particles.30,31 Classical nucleation theory also

predicts that increases in concentration or S should increase the nucleation rate and produce smaller particles. However, neither effect was observed. B. Effect of RESOLV Variables. RESOLV experiments were carried out by directly expanding the CO2 + TBTPP solution at the same preexpansion conditions (C, Tpre, Ppre, and S) as in RESS, but into a liquid receiving solution instead of air. The idea was to capture the particles in the liquid immediately after exiting the nozzle in order to minimize particle growth in the free jet. It was expected that expanding directly into liquid would minimize the collision of particles during expansion and produce smaller primary particles. B1. Effect of Stabilizers on Dispersibility of TBTPP Nanoparticles. Because TBTPP is insoluble in water, aqueous solutions were used as the receiving solutions. However, water is not a good dispersing medium for hydrophobic TBTPP nanoparticles (90°) compared to that of 0.05 wt % Silwet L77 solution (10.6°) because TBTPP, being a fluorinated compound, has a very low surface energy.46 Although PVP slightly improved the wetting properties of water, these properties were significantly increased in dilute solutions of Pluronic F68, SDS, and Silwet L77. However, as SL/S increased from -49.8 to -38.7 to -0.4 mN/m, suspension instability due to the solubilization of TBTPP nanoparticles in the receiving solutions occurred, resulting in a change in particle morphology from nanospheres to nanorods in the SDS solution (Figure 7b) and an increase of particle size in the Silwet L77 solution (Figure 7c). The solubility of organic particles in dilute aqueous surfactant solutions is known to increase with an improvement in the wetting properties of the liquids.33,47 Thus, a stabilizer with too much wetting can have an adverse effect on the dispersion stability of organic nanoparticles.23 On the other hand, results indicate that a moderate wetting agent such as Pluronic F68 is effective for maintaining the size and morphology of the TBTPP particles produced by RESOLV. In fact, moderately wetting stabilizers may be ideal for rapid expansion processes, as particles with very large surface areas are created, and intimate mixing between those particles and the receiving solution is provided by the free jet. B2. Effect of C, Tpre, Ppre, and S on TBTPP Nanoparticles. To determine the effect of RESOLV on particle growth, experiments were carried out by expanding the CO2 + TBTPP mixture into the 0.025 wt % Pluronic F68 solution at the same preexpansion conditions as in RESS. As shown in Table 1, TBTPP nanoparticles with an average size of less than 30 nm were consistently produced, independent of Tpre, Ppre, C, and S. Particle size distributions (PSDs) comparing RESOLV and RESS at Tpre of 40 and 100 °C are shown in Figure 8. Although the nanoparticles produced by RESOLV were only slightly smaller than those produced by RESS at a Tpre of 40 °C, RESOLV at Tpre ) 70 °C reduced particle growth by a factor of 2, and at Tpre ) 100 °C by a factor of almost three. Clearly, the particle growth and aggregation/agglomeration that occur in RESS at the higher preexpansion temperatures is suppressed in the receiving solution. In contrast with RESS, where no effect was observed, particle agglomeration increased with solute concentration in RESOLV.

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Figure 9. FESEM micrographs of nanoparticles obtained from RESOLV of a 1 wt % TBTPP solution in CO2 with 0.9 S at (a) Tpre ) 70 °C, Ppre ) 288 bar; (b) Tpre ) 100 °C, Ppre ) 303 bar. Figure 8. PSDs of TBTPP nanoparticles obtained from RESOLV and RESS of 0.1 wt % TBTPP, S ) 0.1 at (a) Tpre ) 40 °C, Ppre ) 273 bar; (b) Tpre ) 100 °C, Ppre ) 298 bar.

At 0.1 wt % (0.2 mg/mL) TBTPP, nanoparticles were typically well-dispersed, as is shown in Figure 7d. At 1 wt % (2 mg/ mL) TBTPP, the majority of nanoparticles were still welldispersed, but some were agglomerated. Sections of a sample containing severe agglomeration are shown in Figure 9, parts a and b. As Tpre increased from 70 to 100 °C, additional agglomeration was observed and the particles appeared to be more fused together, forming spherical-shaped aggregates with an average diameter of 63 ( 11 nm (Figure 9b). Why the particles are fusing together is unclear, because the temperature of the free jet is still very low (i.e., in RESS, we measured a temperature of -58 °C at 2.5 mm from the nozzle exit for Tpre ) 100 °C and Ppre ) 298 bar). One explanation is that the particle temperature is significantly higher than that of the flow field because of energy release during coalescence of nanoparticles.48 Another contributing factor could be that the melting point of the initially formed nanoparticles is much lower than that of bulk material (e.g., the melting points of bulk Sn vs 10 nm particles of Sn are 232 and 154 °C, respectively).49 Comparing our results with RESOLV to those of other researchers, we note that the average diameters and standard deviations of our TBTPP nanoparticles (dhp ) 24-32 nm, σ ) 6-10 nm) are in the same range as the ibuprofen and poly(HDFDA) nanoparticles (dhp ) 25-43 nm, σ ) 5-10 nm) produced by Sun and co-workers.16,17 Our particles are much smaller than the cyclosporin particles (40-920 nm) produced by Young et al.18,19 and are similar in size to the smaller PSD modes for β-sitosterol (5-50 nm) and phytosterol (12-55 nm) obtained by Tu¨rk and co-workers.10,20 However, they also obtained much larger modes of PSD ranging from 120 to 200 nm for β-sitosterol10 and from 60 to 540 nm for phytosterol,20 which were claimed to be due to agglomeration of the smaller

particles. Finally, we note that both Young et al. and Tu¨rk and co-workers used dynamic light scattering (DLS) for particle size measurement. Unlike scanning electron microscopy (SEM), DLS cannot be used to distinguish between individual particles and agglomerates. In any case, our results agree with Young et al. and Tu¨rk et al. in that particles produced by RESOLV are smaller than those obtained from RESS. C. Proposed Mechanism for Particle Growth in RESS Free Jet. It is of interest to explain our results in terms of the collision-coalescence theory developed by Friedlander and coworkers.50-52 The focus of their work is on producing inorganic nanoparticles via gas-phase reactions in aerosol reactors, and they have developed rate equations to predict the sizes of the nanoparticles produced. However, unlike current RESS modeling work, the material properties of the particles themselves are explicitly included in their analyses. In his work, Friedlander assumes that nucleation is rapid compared with particle collision and coalescence (i.e., coagulation). The growth of particles is assumed to be primarily due to coagulation because condensation processes can be ignored for high-melting-point inorganic materials. These assumptions are, in fact, also reasonable for rapid expansion processes, as condensation is generally assumed to be less important than either nucleation or coagulation.15 Whether collision between two particles of a given size will result in fusion and the formation of a larger particle depends on the rates of collision and coalescence. The coalescence rate depends primarily on the solid-state diffusion coefficient D, where D ∝ exp(-Tm/T).53,54 Here Tm is the melting point of the solute and T is the particle temperature. Solid-state diffusion occurs when the particles are in contact, and the molecules from each particle are transported across the particle surface in the contact region, resulting in particle fusion. Figure 10 shows how Friedlander’s collision-coalescence theory can be used to qualitatively explain the increase in particle size with Tpre in RESS. The temperature at which the charac-

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Sane and Thies

Figure 10. Collision-coalescence theory can be used to explain why higher Tpre lead to larger particle sizes in RESS.

TABLE 3: Size of Particles Produced by RESS Can Be Related to Tm and Tpre through the Solid-State Diffusion Coefficient solute

Tm [°C]

Tpre [°C]

Ppre [bar]

Tpre [K]/ Tm [K]

dhp [nm]

TBTPP, our work

388

lovastatin β-sitosterol

191 140

benzoic acid

122

phenanthrene naphthalene

100 80

40 70 100 105 75 115 77 115 145 130 100 87 105

287 288 303 379 300 300 300 300 300 200 200 204 203

0.47 0.52 0.56 0.81 0.84 0.94 0.89 0.98 1.06 1.02 1.00 1.02 1.07

45 57 76 1804 20010 18010 21010 29010 34010 2000-80008 1000-50008 5000-80007 8000-100007

teristic times for collision and coalescence, defined as the average time between binary particle collisions (τc) and the time for two particles to coalesce (or fuse) after making contact (τf), are equal is defined as TD.51 When the particle temperature is higher than TD, coalescence occurs more rapidly than collision (τf < τc). As the temperature decreases, τf increases considerably faster than τc due to a rapid decrease in the solid-state diffusion coefficient of the material. Eventually, the temperature decreases below TD, coalescence stops and further collisions result only in the agglomeration of individual particles (τf > τc). RESS at higher Tpre (Tpre,H) produces larger primary particles than at lower Tpre (Tpre,L) because the coalescence of particles occurs faster and longer before the temperature decreases to TD. Collision-coalescence theory can also be used to explain why our TBTPP particles are considerably smaller than particles produced from other compounds. A review of the RESS literature shows that smaller particles are generally produced for organic solutes when there is a large difference between Tm of the solute and Tpre, with TBTPP having the highest temperature difference (348 °C) of solutes tested (see Table 3). Because the solid-state diffusion coefficient D ∝ exp(-Tm/T), the coalescence rate of particles from high-melting-point materials is considerably lower than that of low-melting-point materials. In addition, the solid-state diffusion coefficient increases rapidly at temperatures above 0.75 Tm.55 As seen in Table 3 for Tpre/ Tm, only in our work was the preexpansion temperature Tpre below this point. As an alternative explanation to collision-coalescence theory for why we can produce nanoparticles from TBTPP, we also considered the interfacial tension behavior between TBTPP solute and the solvent phase. First, surface tensions of organic solids and polymers are, unlike the solid-state diffusion coefficient, only weakly dependent on temperature. Second, we know from the work of Eggers and co-workers56 that the

interfacial tension for solutes in supercritical fluids ranges from a low of zero for low molecular weight, low-melting solids and increases in a fairly linear manner to 20-60 mN/m at ambient pressures for compounds such as those shown in Table 3. For polymers and other compounds that never reach complete solubility in the supercritical fluid, the interfacial tension remains at small positive values (e.g., ∼10 mN/m)57 at high pressures. Thus, based on known literature values for other highly fluorinated solids at ambient conditions46 and on Egger’s work, we can bound the range of expected interfacial tension values for TBTPP + CO2 during the RESS process from ∼5 to 20 mN/m. Such values are not significantly different from the behavior of other RESS systems presented in the literature. Third, we looked at what RESS modeling work says about the effect of interfacial tension. Weber et al.14 found that for the CO2 + phenanthrene system, doubling the interfacial tension from the assumed value of 19 mN/m reduced the particle size by only 12%, while halving the interfacial tension increased particle size by 19%. For their model, Franklin et al.13 assumed a much lower value (i.e., 1 mN/m) of the interfacial tension for their highly miscible mixture of liquid perfluoropolyether diamide in CO2. In exploring the sensitivity of their model to 5-fold increases/decreases in interfacial tension, they found that lower interfacial tension produced smaller nucleating droplets in the expansion nozzle, but that this effect was obviated by the time the nozzle exit was reached, with lower interfacial tensions producing larger droplets past the nozzle exit. Thus, both modeling efforts predict that if interfacial tension effects are important, the TBTPP + CO2 system, with the lower surface free energy of the fluorinated TBTPP, should produce larger particles than have been observed for the RESS of the solid compounds shown in Table 3. In summary, then, an analysis of the possible role of interfacial tension on particle size in the TBTPP system produces no evidence that it plays a significant role in the determination of particle size. Conclusions We have demonstrated that RESS and RESOLV can be used to consistently produce spherical nanoparticles of TBTPP in the form of nanopowders (38 ( 9 nm) and nanosuspensions (28 ( 9 nm), respectively. During RESOLV, the particle growth that occurs at higher preexpansion temperatures was suppressed by the use of the stabilizing agent Pluronic F68 in the receiving solution. Pluronic F68 plays an important role in the receiving solution by enhancing wetting, preventing collisions, and stabilizing the TBTPP nanoparticles. Contact-angle measurements and spreading coefficients proved to be useful indicators for assessing the suitability of a given stabilizer for our TBTPP + CO2 system. Our success in using the solid-state diffusion coefficient of the solute to qualitatively explain the various particle sizes that have been produced by RESS suggests that this material property needs to be explicitly accounted for in future RESS modeling efforts. Finally, our work indicates that for certain organics and polymers, RESOLV can be a useful technique for producing stable suspensions of well-dispersed and uniform nanoparticles, with the process requiring relatively small amounts of stabilizing agents and being amenable to commercial scale-up. Acknowledgment. This work was supported primarily by the National Science Foundation under the auspices of the ERC Program (Award No. EEC-9731680) and by the NSF-EPSCoR program (EPS-0132573). The authors thank Prof. Ya-Ping Sun and Shelby Taylor from the Department of Chemistry at

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