Langmuir 1997, 13, 1519-1528
1519
Stabilized Polymer Microparticles by Precipitation with a Compressed Fluid Antisolvent. 2. Poly(propylene oxide)and Poly(butylene oxide)-Based Copolymers Simon Mawson, Matthew Z. Yates, Mark L. O’Neill, and Keith P. Johnston* Department of Chemical Engineering, University of Texas, Austin, Texas 78712-1062 Received October 21, 1996. In Final Form: January 17, 1997X Block copolymers containing either poly(propylene oxide) (PPO) or poly(butylene oxide) (PBO) stabilizer group(s) and a poly(ethylene oxide) (PEO) anchor group prevent flocculation of amorphous poly(methyl methacrylate) (PMMA) microparticles formed by spraying PMMA solutions into flowing liquid CO2 at 23 °C. When dissolved PPO-PEO-PPO triblock and PBO-PEO diblock copolymers are introduced with the CO2 feed stream, 0.1-0.5 µm primary PMMA particles are produced. However, larger, and in some cases more spherical microparticles (0.5-2.0 µm) are formed when these stabilizers are fed via the polymer solution phase, for the same overall quantity of stabilizer. The effectiveness of the stabilizer is described in terms of its concentration and how it partitions between the dispersed phase, the interface, and the CO2 phase. In many cases stabilizers with only moderate solubilities in CO2 are more effective than those with higher or lower solubilities. When the stabilizer is introduced with the solution phase, it does not have to be soluble in CO2 to prevent flocculation. The latex particle size, stability, critical flocculation density, and reversibility of floccuation have been measured in-situ by turbidimetry to understand the mechanism of steric stabilization in supercritical fluids. The size of the primary particles in the product determined by scanning electron microscopy is consistent with in-situ measurements of particle size by turbidimetry.
Introduction Uniform polymeric microspheres and microparticles from 0.1 to 10 µm are of interest for practical applications such as microencapsulation for controlled drug delivery and the production of polymer latexes. Microparticles can be produced by processes such as jet milling; however, it can be difficult to avoid losses, to prevent thermal decomposition, and to control particle size distributions and morphology.1 Recently, spray processes with compressed fluids, including supercritical fluids, have offered new opportunities for producing uniform submicron- and micron-sized particles and fibers. These spray techniques include rapid expansion from a supercritical solution (RESS)2-9 and precipitation with a compressed fluid antisolvent (PCA).10-21 In PCA, the CO2 antisolvent may be a gas, liquid, or supercritical fluid, but it must be miscible with the organic X
Abstract published in Advance ACS Abstracts, March 1, 1997.
(1) Hixon, L.; Prior, M.; Prem, H.; Van Cleef, J. Chem. Eng. 1990, November, 94-103. (2) Matson, D. W.; Fulton, J. L.; Peterson, R. C.; Smith, R. D. Ind. Eng. Chem. Res. 1987, 26, 2298-2306. (3) Tom, J. W.; Debenedetti, P. G. Biotechnol. Prog. 1991, 7, 403411. (4) Phillips, E. M.; Stella, V. J. Int. J. Pharm. 1992, 1-10. (5) Boen, S. N.; Bruch, M. D.; Lele, A. K.; Shine, A. D. In Polymer Solutions, Blends and Interfaces; Noda, I., Rubingh, D. N., Eds.; Elsevier Science Publishers B. V.: Amsterdam, 1992; pp 151-172. (6) Lele, A. K.; Shine, A. D. AIChE J. 1992, 38, 742-752. (7) Lele, A. K.; Shine, A. D. Ind. Eng. Chem. Res. 1994, 33, 14761485. (8) Tom, J. W.; Debenedetti, P. G.; Jerome, R. J. Supercrit. Fluids 1994, 7, 9-29. (9) Mawson, S. M.; Johnston, K. P.; Combes, J. R.; DeSimone, J. M. Macromolecules 1995, 28, 3182-3191. (10) Dixon, D. J. Ph.D. Thesis, The University of Texas at Austin, 1992. (11) Dixon, D. J.; Bodmeier, R. A.; Johnston, K. P. AIChE J. 1993, 39, 127-139. (12) Dixon, D. J.; Johnston, K. P. J. Appl. Polym. Sci. 1993, 50, 19291942. (13) Randolph, T. W.; Randolph, A. D.; Mebes, M.; Yeung, S. Biotechnol. Prog. 1993, 9, 429-435. (14) Yeo, S.; Lim, G.; Debenedetti, P. G.; Bernstein, H. Biotechnol. Bioeng. 1993, 41, 341-346. (15) Yeo, S.-D.; Debenedetti, P. G.; Radosz, M.; Schmidt, H.-W. Macromolecules 1993, 26, 6207-6210. (16) Dixon, D. J.; Luna-ba`rcenas, G.; Johnston, K. P. Polymer 1994, 35, 3997-4006.
S0743-7463(96)01017-7 CCC: $14.00
solvent. The liquid solution is sprayed through an atomization nozzle into concurrently flowing CO2. The two-way mass transfer of solvent into CO2 and CO2 into the solution causes the polymer to precipitate. Compared with the case for conventional liquid antisolvents, diffusion is much faster in both directions in PCA. Rapid phase separation can lead to particles and fibers with submicron features. As an antisolvent, CO2 is also benefical because it is inexpensive, nontoxic, nonflammable, and environmentally benign. In addition the critical conditions, i.e., Tc ) 31 °C and Pc ) 73.8 bar, are relatively mild. To date it has been difficult to produce uniform microspheres of amorphous polymers by PCA, as flocculation and agglomeration are often present.11,14,21 For amorphous polymer particles the degree of agglomeration upon exposure to CO2 is directly related to the Tg and the viscoelastic behavior of the plasticized polymer.22-25 It is possible to prevent flocculation with steric stabilizers. However, a great number of substances that could be useful as stabilizers do not dissolve in CO2 due to its very low polarizability/volume and hence weak van der Waals forces.26,27 To date only groups with low cohesive energy densities, e.g. fluorocarbons, fluoroethers, fluoroacrylates, and siloxanes, have been shown to be significantly soluble in CO2.9,28-31 (17) Luna-Ba`rcenas, G.; Kanakia, S. K.; Sanchez, I. C.; Johnston, K. P. Polymer 1995, 36, 3173-3181. (18) Mawson, S.; Kanakia, S.; Johnston, K. P. Polymer, in press. (19) Falk, R.; Randolph, T.; Meyer, J. D.; Kelly, R. M.; Manning, M. C. Pharm. Res., in press. (20) Mawson, S.; Kanakia, S.; Johnston, K. P. J. Appl. Polym. Sci., in press. (21) Mawson, S.; Johnston, K. P.; DeSimone, J. M. Macromolecules 1996. (22) Chiou, J. S.; Barlow, J. W.; Paul, D. R. J. Appl. Polym. Sci. 1985, 30, 2633-2642. (23) Condo, P. D.; Johnston, K. P. J. Polym. Sci.: Part B, Polym. Phys. 1992, 32, 523-533. (24) Condo, P. D.; Paul, D. R.; Johnston, K. P. Macromolecules 1994, 27, 365-371. (25) O’Neill, M. L. Ph.D. Thesis, Carleton, 1994. (26) Consani, K. A.; Smith, R. D. J. Supercrit. Fluids 1990, 3, 51-65. (27) McFann, G. J. Ph.D. Thesis, The University of Texas at Austin, 1993.
© 1997 American Chemical Society
1520 Langmuir, Vol. 13, No. 6, 1997
Mawson et al.
Table 1. Molecular Architecture and Phase Behavior of the Homopolymer and Copolymer Stabilizers Used in this Study stabilizer
Mw
poly(ethylene oxide) (PEO)
poly(butylene oxide) (PBO) poly(butyl acrylate)c (PBA) Pluronic 17R2 (PPO-b-PEO-b-PPO)
∼420
Pluronic 17R4 (PPO-b-PEO-b-PPO) Pluronic 25R2 (PPO-b-PEO-b-PPO)
2800 3000
∼1120 ∼600
Tetronic 90R4e (2(PPO)-b-PEO-b-2(PPO)) Tetronic 150R1e (2(PPO)-b-PEO-b-2(PPO)) SAM185 (PBO-b-PEO)
6700 7400 1500
∼2700 ∼740 ∼660
SAM187 (PBO-b-PEO)
2400
poly(propylene oxide) (PPO)
a
e
PEO Mw
400 600 1025 2000 4000 800 NAb 2100
b
400 600
∼1540 c
conc (wt %)
temp (°C)
cloud point (bar)
0.85 0.39 0.50 0.50 0.50d 0.50 NA 0.20 0.0055 0.13 0.13 0.05 0.150d 0.27d 0.05 0.0055 0.5d
25 25 30 25 25 25 25 25 23/35 25 25 25 25 25 23 23/35 25
88a 176a 81 178a 276a 121a 345a >345a 124 117/138 >345
(14 bar due to polydispersity. NA ) not available. Poly(butyl acrylate) fractionated with CO2 at 172 bar. Tetrafunctional structure.
Recently, the homopolymer poly(1,1-dihydroperfluorooctyl acrylate) (PFOA) and the diblock copolymer polystyrene (PS)-b-PFOA have been added to CO2 to prevent flocculation and agglomeration of poly(methyl methacrylate) (PMMA) and PS latexes produced by dispersion polymerization32-34 and PMMA latexes produced by PCA.21 For PCA, it was found that adsorption of the stabilizer at the interface between the microparticles and solution commenced in the jet on the order of several tenths of milliseconds and continued for seconds throughout the precipitator. Polymer dispersions have been studied in-situ for the first time in CO2 to understand stabilization and flocculation mechanisms by turbidimetry and dynamic light scattering.35,36 The high affinity of fluorinated molecules for CO2 has been well documented.9,21,26,28-31,37-39 Fluorinated stabilizers including fluoroacrylates and fluoroethers are however quite expensive and often insoluble in conventional organic solvents.40 These limitations are not of concern for block copolymers based upon poly(ethylene oxide) (PEO), poly(propylene -oxide) (PPO), and poly(butylene oxide) (PBO). PPO-PEO-PPO and PBO-PEO block copolymers with molecular weights from 1500 to 7400 g/mol have been shown to be soluble in CO2 at moderate temperatures and pressures.41,42 It was found (28) Hoefling, T. A.; Enick, R. M.; Beckman, E. J. J. Phys. Chem. 1991, 95, 7127-7129. (29) DeSimone, J. M.; Guan, Z.; Elsbernd, C. S. Science 1992, 257, 945-947. (30) Kissa, E. Fluorinated Surfactants Synthesis, Properties, Applications; Marcel Dekker, Inc.: New York, 1994; Vol. 50. (31) Harrison, K. L.; Goveas, J.; Johnston, K. P.; O’Rear, E. A. III. Langmuir 1994, 10, 3536-3541. (32) DeSimone, J. M.; Maury, E. E.; Menceloglu, Y. Z.; McClain, J. B.; Romack, T. J.; Combes, J. R. Science 1994, 265, 356. (33) Hsiao, Y.-L.; Maury, E. E.; DeSimone, J. M.; Mawson, S.; Johnston, K. P. Macromolecules 1995, 28, 8159-8166. (34) Canelas, D. A.; Betts, D. E.; DeSimone, J. M. Macromolecules 1996, 29, 2818-2821. (35) Yates, M. Z.; O’Neill, M. L.; Johnston, K. P.; Webber, S.; Caneles, D. A.; Betts, D. E.; DeSimone, J. M. Macromolecules, submitted. (36) O’Neill, M. L.; Yates, M. Z.; Harrison, K. L.; Johnston, K. P.; Canelas, D. A.; Betts, D. E.; DeSimone, J. M.; Wilkinson, S. P. Macromolecules, submitted. (37) Yee, G. G.; Fulton, J. L.; Smith, R. D. J. Phys. Chem. 1992, 96, 6172-6181. (38) McHugh, M. A.; Krukonis, V. J. Supercritical Fluid Extraction Principles and Practice, 2nd ed.; Butterworths: Stoneham, MA, 1994. (39) Wilson, E. K. Chem. Eng. News 1996, April 15, 27-28. (40) Shaffer, K. A.; Jones, T. A.; Canelas, D. A.; DeSimone, J. M.; Wilkinson, S. P. Macromolecules 1996, 29, 2704-2706. (41) Takishima, S.; O’Neill, M. L.; Johnston, K. P. In preparation. (42) O’Neill, M. L.; Fang, M.; Harrison, K. L.; Cao, Q.; Sieberg, J. F.; Johnston, K. P. J. Supercrit. Fluids, submitted.
d
Partial solubility.
that PEO is insoluble in CO2, while PPO and PBO are moderately soluble. Thus the block copolymers of PEO/ PPO or PEO/PBO have the potential to be interfacially active in CO2. Interfacial activity is critical for steric stabilization to occur. The first objective of this study was to stabilize polymer latexes in CO2 formed during PCA with PPO-PEO-PPO triblock and PBO-PEO diblock copolymers. PMMA was chosen as the polymer, since it is highly plasticized by CO2, making it prone to agglomeration, and is biocompatible.43 Because of the varying solubilities of the copolymer stabilizers used in this study, the stabilizers were introduced dissolved in either CO2 or the polymer solution. The second objective was to characterize the mechanism of steric stabilization and flocculation of these latexes. In-situ turbidimetry measurements were used to determine the stability and average particle size of the latex and the reversibility of flocculation. Experimental Section Materials. Poly(methyl methacrylate) (PMMA) with a Mw of 75 000 was purchased from Scientific Polymer Products Inc. Spectrophotometric grade methyl ethyl ketone (MEK) (Mallinkrodt) and tetrahydroduran (THF) (EM Science) were used as received. All of the surfactants tested in this study were block copolymers comprised of PPO, PBO, and PEO, as shown in Table 1. Pluronic 17R2, 17R4, and 25R2 (BASF) are PPO-PEO-PPO triblock copolymers. The first two digits when multiplied by 100 indicate the approximate PPO Mw. The last digit multiplied by 10 gives the percent PEO in each polymer. Tetronic 90R4 and 150R1 (BASF) had the highest molecular weights. Tetronic surfactants are tetrafunctional block copolymers, which have four alkylene oxide chains connected to the central ethylenediamine group.44 SAM185 and -187 are PEO-PBO diblock surfactants (Pittsburgh Paint and Glass Co.). PCA Apparatus. The PCA apparatus and operating procedure for stabilizing microparticles with CO2-based surfactants have been described in greater detail in our previous paper.21 For all experiments, the polymer solution was sprayed into flowing CO2 in a 1.27 cm i.d., 13 mL sapphire tube to visually observe precipitation. A 50 µm i.d. × 16.5 cm long fused silica capillary tube (Polymicro Technology) was used to atomize the polymer solution (with or without surfactant) into CO2. A coaxial spray nozzle was used to introduce the CO2 at a high velocity in (43) Wang, H. M. S. Thesis, The University of Texas at Austin, 1993. (44) BASF Corporation, “BASF Performance Chemicals: Products for the Manufacture, Stabilization and Formulation of Latex Polymers”.
Stabilized Polymer Microparticles
Figure 1. Schematic of the PCA apparatus used for viewing the sprays and producing particles for SEM analysis.
Figure 2. Schematic of the PCA apparatus used for in-situ turbidimetry. an annular region about the capillary tube.20 Microparticle samples were collected in-situ on a 1/16 in. o.d. × 3/4 in. long section of stainless steel tubing.21 The latex morphology was analyzed and imaged with a Jeol JSM-35C scanning electron microscope (SEM). Samples were sputter coated with goldpalladium to a thickness of approximately 200 Å. Turbidimetry Apparatus. A schematic of the PCA turbidimetry apparatus is shown in Figure 2. The turbidimetry cell contains two sapphire windows, 3/8 in. in diameter by 1/8 in. thick, positioned opposite each other. To accommodate the capillary atomizaton nozzle, a 1 in. section of 1/4 in. o.d. tubing was welded to a 1 in. × 3/8 in. thick aluminum disk, which was sealed to the cell with a teflon o-ring. The PCA pressurizing assembly has been described in detail elsewhere.18,20,21 For CO2-based stabilizers, known amounts of stabilizer and CO2 were placed into the turbidimetry cell. The stabilizer solution was agitated using a stir bar and an air-driven immersible magnetic stirrer (Matheson Scientific, Model 214-858). The surfactant cloud point was obtained by reducing the pressure and observing a significant increase in solution turbidity. The cloud point was also confirmed by visual observation. The polymer solution was injected into the PCA turbidimetry apparatus from a stainless steel tube, 1 in. o.d. × 11/16 in. i.d. × 8 in. long (Autocloave Eng., model CNLX 1608-316). This vessel contained a movable piston which was fitted with two Buna-N O-rings and had a usable volume of 36 mL. The pressurizing fluid on the upstream side of the piston was CO2. The CO2 pressure was controlled by an automated syringe pump (ISCO,
Langmuir, Vol. 13, No. 6, 1997 1521 model 100DX). As shown in Figure 2, CO2 from the syringe pump was used to pressurize a second tube with the same dimensions to control the density of the stabilized latex in CO2. The turbidimetry cell had a path length of ∼3.0 cm. The turbidity measurements were recorded versus time with a Cary 3E UV-vis spectrophotometer (Varian) every 5 s for an incident wavelength of 650 nm. After we collected turbidity data for 1020 min, the pressure was decreased without agitation while we continued taking readings. The pressure was decreased in increments from 138 bar (F ) 0.878 g/mL) to 83 bar (F ) 0.789 g/mL) at 23 °C or 179 bar (F ) 0.848 g/mL) to 83 bar (F ) 0.568 g/mL) at 35 °C. Before and after the turbidity measurements the latex was scanned from 400 to 800 nm. The latex particle size was then estimated using the turbidity ratio method.45 All experiments were reproduced at least once. PCA and Turbidimetry Theory. The key features of the microparticle formation mechanism in PCA include the breakup of the liquid jet, the mass transfer pathway through the phase diagram, the collisions and drying of the suspended droplets, and the plasticization of the polymer by CO2 (and residual solvent). The jet breakup mechanism can be described by the dimensionless Weber number (NWe).13,14 The NWe is the ratio of the inertial forces to surface tension forces and is given by NWe ) FAv2∆/γ, where FA is the antisolvent density, v is the velocity of the jet relative to that of the CO2, D is the jet diameter, and γ is the interfacial tension. In PCA, the jet hydrodynamics are dominated by atomization rather than Raleigh instabilites because of the high solution velocity, small interfacial tension, and high CO2 density.4,36 The solution mass transfer pathway may be broken into two parts: atomization and jet breakup followed by recirculation and suspension of the particles throughout the entire precipitation vessel. In the coaxial nozzle, the solution is sprayed through a tube surrounded by an annulus with flowing CO2. With this coaxial nozzle the CO2 velocity is high relative to a standard nozzle with a low CO2 velocity. Atomization in the jet is less prevalent due to the smaller relative velocity between the solution phase and the continuous phase. However, recirculation and mixing of the suspended droplets is much more intense due to the high velocity CO2. An alternative method for mixing would be mechanical stirring. This enhanced mixing has been found to be beneficial to the formation of particles with minimum flocculation.21 While the characteristic time for precipitation in the first 0.1 cm of the jet is 10-4 s, stabilization of the suspensions throughout the precipitator is estimated to be on the order of seconds. The phase separation mechanism can be described by a ternary phase diagram and its accompanying mass transfer pathways.11,12,17,18 With the dilute solutions used in this study, the mass transfer pathway crosses the binodal curve below the plait point (critical point). Hence, polymer-rich domains nucleate and grow within a solvent continuous phase. After crossing the spinodal into the metastable region, the remaining phase separation takes place by spinodal decomposition. Polymer vitrification occurs when the mass transfer pathway crosses into the glassy region of the phase diagram. Because of plasticization by CO2, amorphous PMMA microparticles do not vitrify until the solution is depressurized at the end of the experiment. It is this plasticization which is largely responsible for agglomerating flocculated microparticles. Because the particle sizes are comparable to the wavelength of visible light, the turbidity of the dispersion can be determined from Mie theory. For a monodisperse suspension of spherical particles turbidity is given by τ ) 3K*c/2FD, where K* is the scattering coefficient, c is the concentration of the dispersed phase, F is the dispersed phase density, and D is the droplet diameter.46 The size of the latex particles can be estimated using the turbidity ratio method. In this method, the ratio of measured turbidities at two different wavelengths is equal to the ratio of scattering coefficients at the same wavelengths.45 An average droplet size is estimated by iteration of the calculated ratio of scattering coefficients to match the measured ratio of turbidities. Provided that the particle diameter λ/4 e d e 10λ, the turbidity ratio (45) Melik, D. H.; Fogler, H. S. J. Colloid Interface Sci. 1983, 92, 161-180. (46) Kourti, T., MacGregor, J. F., Hamielec, A. E., Kourti, T., MacGregor, J. F., Hamielec, A. E., Eds.; American Chemical Society: Boston, 1991; pp 1-63.
1522 Langmuir, Vol. 13, No. 6, 1997
Mawson et al. Table 2. Latex Particle Size from in-Situ Turbidimetry for PMMA in CO2 with Various Stabilizers particle size (µm) stabilizer none
method can provide a unique solution for average particle size. This method requires that the refractive index be known for both the PMMA- and CO2-rich phases. The refractive index of the CO2 phase was assumed to be that of pure CO2 even though a small amount of THF was present. The CO2 refractive index is available from the literature.47 However, the PMMA droplets will be highly swollen by CO2, and the refractive index of the CO2/PMMA mixture is unknown. An estimate of the droplet refractive index was made by assuming 35 vol % CO2 in PMMA at 138 bar and 30 vol % CO2 in PMMA at 69 bar.48 The LorentzLorenz equation for mixtures was then used to estimate the refractive index of the PMMA/CO2 mixture.49 These assumptions give a ratio of refractive indices of droplet to continuous phase of approximately 1.15 at 138 bar and 1.2 at 69 bar. Scattering coefficients were then estimated by interpolation of tabulated values calculated from Mie theory.50
Results and Discussion PMMA in CO2 Latex without Stabilizer. When a 1.0 wt % PMMA in MEK solution is sprayed into CO2 without any stabilizer, highly flocculated 0.1-1.0 µm primary microparticles are formed with a “cobweb-like” morphology, as shown in Figure 3, as has been reported previously.11,20,21 During precipitation, several visual observations were recorded. For the first 15 s of the 25 s spray, very fine PMMA microparticles recirculated throughout the entire vessel. After 15 s individual particles were observed within the otherwise uniform suspension of PMMA precipitate, indicating the onset of extensive flocculation. Once flocculation had begun the PMMA latex particles accumulated on the inside wall of the sapphire precipitator. Latexes of PMMA in CO2 without any stabilizer were studied by turbidimetry to provide a baseline for the stabilized systems. A 1.0 wt % PMMA in CO2 solution was atomized into CO2 at 23 °C and 138 bar. For the turbidity experiments about 15 s of spray provided an optimal amount of turbidity for the measurements. Longer spray times can lead to more concentrated latexes with undesirable multiple scattering. At 23 °C a constant decrease in the latex turbidity with time, |dτ/dt|, of 0.0056 cm-1/min was observed over 100 (47) Burns, R. C.; Graham, C.; Weller, A. R. M. Mol. Phys. 1986, 59, 41. (48) McHugh, M. A.; Liau, I. S. In Supercritical Fluid Science and Technology; Johnston, K. P., Penninger, J. M. L., Eds.; Elsevier Science Publishers B.V.: Amsterdam, 1985; pp 415-434. (49) Heller, W. J. Phys. Chem. 1965, 69, 1123-1129. (50) Heller, W.; Pangonis, W. J. J. Chem. Phys. 1957, 26, 498-506.
NAb NA
NA
Pluronic 17R2 CO2 0.0055
0.96
SAM185
0.01 CO2 0.0055
1.72 0.96
Pluronic 17R4 Pluronic 25R2 SAM185 SAM187 Tetronic 90R4
soln soln soln soln soln
d
Figure 3. SEM micrographs of PMMA precipitated by spraying a 1.0 wt % PMMA/MEK solution through a 50 µm coaxial capillary nozzle into CO2 at 23 °C and 124.1 bar without any stabilizer.
surf. conc g of stab./ temp F ) 0.878 F ) 0.789 phase (wt %) g of PMMA (°C) g/mL g/mL
0.01 1.0 1.0 1.0 1.0 0.1
1.72 1.0 1.0 1.0 1.0 0.1
23 35a 23 35a 23 23 35 23 23 23 23 23 23
1.61 1.44 0.60 0.56c 0.56 0.63 0.58c 0.45 1.15 1.06 1.92 1.70 1.01
NAb,d NAd NAd NAd 1.32 NAb NAb 0.73 1.39 1.74 1.75 1.41 0.97
a F ) 0.568 g/mL. b NA ) not applicable. c Heated from 23 °C. Complete sedimentation after depressurization.
min as the density of the CO2 was decreased in increments from 0.878 g/mL (P ) 138 bar) to 0.789 g/mL (P ) 83 bar). The initial size of the latex particles was estimated to be ∼1.61 µm (Table 2) from the 700 nm/800 nm turbitity ratio (m ) 1.15). By the end of the experiment the cell was clear due to sedimentation of the latex. Consequently, the particle size could not be estimated at 83 bar. At 35 °C, a constant value for |dτ/dt| of 0.004 cm-1/min was observed as the density was decreased in increments from 0.848 g/mL (179 bar) to 0.700 g/mL (83 bar). When the density was decreased to 0.568 g/mL, the flocculation and subsequent sedimentation increased the rate of decay in turbidity dramatically to 0.93 cm-1/min. The refractive index ratio changes from approximately 1.15 at the highest density to 1.20 at the lowest density. The change in turbidity caused by the change in refractive index changes should be directly proportional to the change in the scattering coefficient, K*. To determine the relative change in turbidity due to the change in the CO2 refractive index, a scattering coefficient was calculated for a given size at a refractive index ratio of 1.15 or 1.20. These calculations show that for the smallest particles formed, ∼500 nm, the turbidity should increase approximately 40% as the pressure is lowered from 2000 to 1100 psi. However, for the largest particles observed, ∼2800 nm, the turbidity is expected to decrease approximately 30% as the pressure is lowered from 2000 to 1100 psi. For each decrease in density, no discontinuity in turbidity was observed. Thus, it is likely that, for a polydisperse latex, the two effects cancel each other so that the measured change in turbidity due to refractive index changes is small.50 Latex Formation with Stabilizer Introduced with the CO2 Phase. When a diblock copolymer with a CO2philic tail and CO2-phobic anchor group is added to the CO2 continuous phase, latex stabilization can occur by a steric mechanism.21,32,35,36 Consequently, the phase behavior of the stabilizer in the continous phase must be known in order to determine the minimum experimental pressure for a given temperature, if it is desired to fully solubilize the surfactant. The cloud points for the various stabilizers are listed in Table 1. Detailed phase behavior diagrams are available elsewhere for PPO and PEO homopolymers and Pluronic 17R2, 17R4, and 25R2 triblock copolymers.42 Table 1 shows that 1000 Mw PPO is more soluble than 800 Mw PBO, which in turn is more soluble than 600 Mw PEO and that increasing the stabilizer Mw decreases solubility in CO2. A summary of the experimental results for the PMMA microparticles stabilized with dissolved surfactants fed
Stabilized Polymer Microparticles
Langmuir, Vol. 13, No. 6, 1997 1523
Table 3. Visual Observations of Flocculation and Accumulation on the Sides of the Sapphire Tube during the Spray and Morphology from SEM for 1.0 wt % PMMA in MEK Solutions Precipitated into CO2 at 23 °C and 149 bara stabilizer SAM185 Pluronic 17R2
PPOb + 17R2 PPOb none a
surf. conc (wt %)
g of stab./ g of PMMA
visual flocc
visual accum
primary particles (µm)
microparticle macrostructure
0.01 0.05 0.0012 0.0036 0.01 0.053 0.0064c 0.0102d 0.041
1.14 5.42 0.13 0.39 1.14 5.71 0.70 1.11 4.46
no no yes no no no yes yes yes yes
no no yes slight no no yes yes yes yes
0.1-0.5 0.1-0.5 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0 0.1-1.0
ind & sl flocc 1-2 µm ind & sl flocc 0.5-1.0 µm flocc cobweb flocc cobweb ind & sl flocc 1-2 µm ind & sl flocc 0.5-1.0 µm flocc cobweb flocc cobweb flocc cobweb flocc cobweb
The stabilizers were introduced in the CO2 phase. b Mw ) 1000. c 47% Pluronic 17R2.
d
52% Pluronic 17R2.
Figure 5. Turbidity-time profiles for PMMA latex particles stabilized with 0.01 wt % Pluronic 17R2 and SAM185 introduced into the CO2 phase at 35 °C and various densities above and below the stabilizer phase boundary.
Figure 4. SEM micrographs of PMMA precipitated by spraying a 1.0 wt % PMMA/MEK solution through a 50 µm coaxial capillary nozzle into (A, top) 0.01 wt % Pluronic 17R2 in CO2 solution or (B, bottom) 0.01 wt % SAM185 in CO2 solution at 23 °C and 124.1 bar.
in with the CO2 phase is presented in Table 3. This table is arranged from the best to worst performance in terms of preventing flocculation. Figure 4 shows the PMMA morphology obtained after spraying a 1.0 wt % PMMA in MEK solution into CO2 containing 0.01 wt % (1.02 g/g of PMMA) (A) Pluronic 17R2 or (B) SAM185. Clearly there is a dramatic change in the microparticle morphology compared to the case with no stabilizer (Figure 3). Here individual PMMA primary particles are formed which range in size from 0.1 to 0.5 µm with only slight flocculation. The flocs range in size from 1 to 2 µm. When the stabilizer concentration is increased to 0.05 wt %, slightly less flocculation is observed (Table 2). During
precipitation, microparticle flocculation and accumulation on the sides of the spray chamber do not take place, on the basis of visual observations. In attempts to achieve PMMA stabilization with a smaller amount of Pluronic 17R2, this copolymer was mixed with 1000 Mw PPO homopolymer. The composition of the resulting solution was 0.0053 wt % 17R2 and 0.0049 wt % PPO, corresponding to a total stabilizer concentration of 0.0102 wt % (∼50/50 17R2/PPO). During precipitation, flocculation and accumulation on the sides of the vessel occurred, unlike the case with 0.01 wt % Pluronic 17R2 without PPO. Flocculation and accumulation were also observed when 0.041 wt % PPO homopolymer was used alone as a stabilizer for times upto 26 s. The turbidity-time profiles for the PMMA latex stabilized at 35 °C with 0.0055 wt % (0.96 g/g PMMA) of either Pluronic 17R2 or SAM185 are shown in Figure 5. Because the spray time was decreased to ∼15 s, the stabilizer concentration was lowered to 0.0055 wt % to maintain a constant weight ratio of stabilizer to polymer as in previous experiments. At first a stable latex was formed at 23 °C. From the turbidity ratio, the estimated particle sizes for the Pluronic 17R2 and SAM185-stabilized latexes were 0.60 and 0.63 µm (Table 1), respectively. These particle sizes agree with the sizes of the primary particles determined by SEM shown in Figure 4. A negligible change in particle size occurred after heating the dispersion to 35 °C, as determined by turbidity (Table 2). At the highest densities, i.e., 0.848-0.818 g/mL, the turbidity changes little over 10 min, indicating a stable latex. As the density is lowered to 0.772 g/mL and then to 0.700 g/mL, a large increase in turbidity is observed. For a given volume fraction of dispersed phase the turbidity
1524 Langmuir, Vol. 13, No. 6, 1997
Figure 6. Log |dτ/dt| versus density for PMMA latex particles in CO2 formed with no stabilizer, and with Pluronic 17R2 and SAM185 at 35 °C for the conditions in Figure 5.
increases with flocculation due to an increase in the amount of light scattered by the larger floccs. With an adsorbed block copolymer stabilizer, the onset of latex flocculation is manifested by a dramatic increase in the turbidity.51 The increase in turbidity may also be partially due to phase separation of the stabilizer from CO2. For SAM185 and Pluronic 17R2 (Table 1) phase separation begins at 0.827 and 0.788 g/mL, respectively. When a homogeneous solution of stabilizer and CO2 at a concentration of 0.0055 wt % is depressurized, the turbidity increases by a maximum of ∼0.4 cm-1 at the phase boundary. However, the turbidity increase at 0.700 g/mL is ∼1.0 cm-1 for 17R2 and ∼0.5 cm-1 for SAM185. As mentioned above the turbidity is not affected by the change in the refractive index of CO2. Therefore the additional increase in turbidity is attributed to latex flocculation. From Figure 5, the effect of flocculation upon the turbidity of the latex stabilized with Pluronic 17R2 is far greater than that with SAM185. This increase is consistent with the change in the latex particle size as the density is changed from 0.878 to 0.789 g/mL at 23 °C. For 17R2, the latex particle size increases from 0.56 to 1.32 µm as compared to the increase from 0.45 to 0.73 µm for SAM185 (Table 2). After the turbidity increase at a density of 0.772 g/mL due to flocculation, the latex stability decreases, and so |dτ/dt| increases. This decrease in stability is sharper for 17R2, compared to SAM185. At 0.629 g/mL, another significant increase in the turbidity occurs for the SAM185stabilized latex. Because the SAM185 phase separates at ∼0.827 g/mL, most of this increase is attributed to flocculation rather than the precipitation of stabilizer from solution. After the latex flocculates, the turbidity decreases sharply over time as sedimentation becomes prevalent. At a density of 0.568 g/mL, sedimentation of both latexes was nearly complete. By increasing the density back to 0.848 g/mL, the latex could not be redispersed with the magnetic stir bar. The slopes of turbidity verses time for PMMA latexes without stabilizer and with 0.01 wt % Pluronic 17R2 or SAM185 at 23 and 35 °C are shown in Figure 6. The latex stability, log |dτ/dt|, was determined quantitatively from the slope of a given decay curve. The transients from the first few minutes of each decay curve were excluded. The vertical dotted lines represent the stabilizer phase boundary. At the higher densities, the constant latex stability of the PMMA-CO2 binary without stabilizer suggests that (51) Napper, D. H. Polymeric Stabilization of Colloidal Dispersions; Academic Press Inc.: New York, 1983.
Mawson et al.
buoyancy and vicosity have little effect on the stability in this region. For densities above the stabilizer phase boundary, it is clear that both stabilizers increase the stability by about an order of magnitude. At the phase boundary, a gradual discontinuity in the slope occurs for both stabilizers, and the latex remains moderately stable below the phase boundary. In this region, latex flocculation is reversible when F is increased back above the stabilizer phase boundary. At the lowest densities, the latex stability is similar to that of the PMMA-CO2 binary, and the latex is not redispersible. As shown in Figure 6, the 17R2- and SAM185-stabilized latexes are an order of magnitude more stable than the latex without stabilizer. As mentioned previously, the polymer solutions were sprayed for 15 s, the PMMA-CO2 latex became significantly less stable due to flocculation, whereas the surfactant-stabilized latex remained stable. For PEHA emulsions in CO2 stabilized with PFOA, O’Neill et al.36 and Yates et al.35 have reported a sharp discontinuity in Log |dτ/dt| versus F, reflecting a point of destabilization of emulsions below the stabilizer phase boundary. Unlike the lower Mw 17R2 or SAM185, the PFOA (Mw ) 1 × 106 g/mol) chains easily span the distance between two or more emulsion droplets, leading to irreversible flocculation by a bridging mechanism. Because the 17R2 and SAM185 stabilizers are too short to span two particles, bridging is not present. As mentioned previously, latex flocculation is reversible when the CO2 density is decreased slightly below the phase boundary. Reversible behavior was observed with a lower Mw PSb-PFOA diblock polymer, where the PFOA Mw was only 24.5 × 103 g/mol. As is the case for the stabilizers in this study, the PFOA chains are too short to lead to significant bridging. Furthermore, the surface coverage appears to be sufficiently high for those surfactants to prevent irreversible flocculation due to Hamaker forces even when the density is lowered 0.1 g/mL below the stabilizer phase boundary. Latex sedimentation due to gravitational forces can be calculated by Stoke’s Law, t ) 9ηh/2∆Fgr2, where t is the sedimentation time, η is the continuous phase viscosity, h is the distance the droplets fall, ∆F is the density difference between the dispersed phase and the continuous phase, and r is the droplet radius. From Stoke’s Law, it is estimated that the time required for 0.5 µm PMMA latex particles to sediment the diameter of the optical aperture, 0.79 cm, in CO2 at 23 °C with a measured density difference of 0.326 g/mL and a CO2 viscosity of 8.88 × 10-4 P is approximately 4.5 h. This is consistent with the large negative values for log |dτ/dt| at high densities, indicating a latex not prone to flocculation or sedimentation. Both thermodynamic and transport issues will influence the mechanism of stabilization of PMMA latexes as they form from THF. On the basis of their molecular structures and solubilities in CO2 and THF, all of the stabilizers may be expected to be much more soluble in PMMA/THF solutions than in CO2. When they start out in the CO2 phase, they will have a strong tendency to diffuse to the CO2-PMMA/THF interface. The thermodynamic driving force for this diffusion will be greater for SAM185 than Pluronic 17R2, since it contains more CO2-phobic PEO groups. The solubility of PEO in CO2 is quite sensitive to the molar mass over this range.42,52 Furthermore, the 840 molar mass PBO tail in SAM185 is less soluble in CO2 (52) Daneshvar, M.; Kim, S.; Gulari, E. J. Phys. Chem. 1990, 94, 2124-2128.
Stabilized Polymer Microparticles
Langmuir, Vol. 13, No. 6, 1997 1525
Table 4. Visual Observations of Flocculation and Accumulation on the Sides of the Sapphire Tube during the Spray and Morphology from SEM for 1.0 wt % PMMA in MEK Solutions Precipitated into CO2 at 23 °C and 149 bara surfactant Pluronic 17R4 Pluronic 25R2 SAM185 SAM187 Tetronic 90R4 PBA Tetronic 150R1 PPO Pluronic 17R2 PPO PEO PBO a
surf. conc (wt %)
visual flocc
visual accum
primary particles (µm)
microparticle macrostructure
0.1 1.0 0.1 1.0 0.1 1.0 0.1 1.0 0.1 1.0 1.0 0.1 1.0 1.0b 0.1 1.0-5.0 1.0c 1.0 1.0
yes no yes no yes no yes no no no yes no no no yes no yes yes yes
yes yes yes no yes no yes no yes no yes yes yes yes yes yes yes yes yes
0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-2.0 0.5-1.0 0.5-1.0 0.5-2.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0 0.5-1.0
flocc cobweb ind & sl flocc 2-4 µm flocc cobweb ind & sl flocc 2-4 µm flocc cobweb ind & sl flocc 2-3 µm flocc cobweb individual microspheres ind, sl flocc & agglom 5-10 µm flocc & agglom 5-10 µm agglom 2-3 µm flocc & agglom 10-20 µm flocc & agglom 10 µm agglom 10-20 µm flocc cobweb flocc cobweb flocc cobweb flocc cobweb flocc cobweb
The stabilizers were introduced in the solution phase. b 4000 Mw. c 2000 Mw.
than each of the two 840 molar mass PPO tails on Pluronic 17R2. Finally, SAM185 is less soluble than Pluronic 17R2 in CO2. This expectation of a greater thermodynamic driving force for diffusional adsorption to the interface of SAM185 relative to Pluronic 17R2 is consistent with its greater effectiveness as a stabilizer at intermediate densities in Figure 5. Latex Formation with Stabilizer Introduced with the Solution Phase. The surfactant feed concentrations in the solution phase (Table 4) were much higher than those in the CO2 phase (Table 3). These concentrations were chosen so that the total mass of the surfactant in the system at the end of the spray was similar in each case. Figure 7 shows the PMMA morphology obtained after spraying a 1.0 wt % PMMA in THF solution containing 1.0 wt % (1.0 g/g of PMMA) Pluronic 17R4 (A) or 25R2 (B) into CO2 at 23 °C. Although both cases lead to individual microparticles ranging in size from 0.5 to 1.0 µm, a significantly larger amount of the smaller 0.5 µm latex particles is formed with Pluronic 25R2. During the spray, visual flocculation and accumulation were clearly absent for both stabilizers (Table 4). When Pluronic 17R2 (Table 2) was added to the solution phase (up to 3.0 wt %) extensive flocculation occurred, unlike the case for the other Pluronics. Figure 8 shows the PMMA morphology obtained after precipitating a 1.0 wt % PMMA in THF solution containing 1.0 wt % (1.0 g/g of PMMA) (A) SAM185 or (B) SAM187 into CO2. For SAM185 (Figure 8A) individual microparticles are formed which range in size from 0.5 to 1.0 µm with slight flocculation, producing larger 2-3 µm groups. In contrast, the particles stabilized with SAM187 (Figure 8 B) range in size from 0.3 to 2.0 µm. Compared to the SAM185-stabilized latex particles, particles with SAM187 are far more spherical and less flocculated. The SAM187stabilized particles were the most spherical of all the particles throughout the study. For both of these PBObased stabilizers, flocculation and accumulation on the inside wall were clearly absent during precipitation. Also, visual flocculation was observed when the stabilizer concentration was decreased to 0.1 wt %. Figure 9 shows the PMMA morphology obtained after precipitating a 1.0 wt % PMMA in THF solution containing (A) 1.0 wt % or (B) 0.1 wt % (0.1 g/g of PMMA) Tetronic 90R4 into CO2. As shown in Figure 9A, 0.1-1.0 µm PMMA microparticles are formed with 1.0 wt % Tetronic 90R4. These flocculated particles have agglomerated into larger
Figure 7. SEM micrographs of PMMA precipitated by spraying a 1.0 wt % PMMA/THF solution containing 1.0 wt % (A, top) Pluronic 17R4 or (B, bottom) Pluronic 25R2 through a 50 µm coaxial capillary nozzle into CO2 at 23 °C and 124.1 bar.
2-5 µm particles. In contrast, far less flocculation and agglomeration are observed with the addition of only 0.1 wt % Tetronic 90R4 (Figure 9B). Flocculation was also absent during precipitation on the basis of visual observation. Similar trends were also observed with Tetronic 150R1, but with slightly more agglomeration.
1526 Langmuir, Vol. 13, No. 6, 1997
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Figure 8. SEM micrographs of PMMA precipitated by spraying a 1.0 wt % PMMA/THF solution containing 1.0 wt % (A, top) SAM185 or (B, bottom) SAM187 through a 50 µm coaxial capillary nozzle into CO2 at 23 °C and 124.1 bar.
Figure 9. SEM micrographs of PMMA precipitated by spraying a 1.0 wt % PMMA/THF solution containing (A, top) 1.0 wt % or (B, bottom) 0.1 wt % Tetronic 90R4 through a 50 µm coaxial capillary nozzle into CO2 at 23 °C and 124.1 bar.
When a 1.0 wt % PMMA in THF solution containing 1.0 wt % (A) poly(butyl acrylate) (PBA) or (B) 4000 Mw PPO homopolymer is precipitated in CO2, a highly agglomerated morphology is produced, as shown in Figure 10. The PBA was fractionated by CO2 at 172 bar. The soluble fraction was utilized and is expected to be partially soluble at the PCA pressure (138 bar). As shown in Table 2, the PPO at 4000 Mw is insoluble in CO2. Although the PMMA microparticles shown in Figure 10 appear to be highly agglomerated, these particles were too small to be seen visually during precipitation. The turbidity-time profiles for 1.0 wt % PMMA (1.0 g/g of PMMA) stabilized with 1.0 wt % Pluronic 17R4, 25R2, and SAM185 added via the solution phase are shown in Figure 11. With 17R4, the turbidity steadily increases over 100 min as the density is changed from 0.878 to 0.789 g/mL. Both the 17R4- and 25R2-stabilized latexes appear to be stable at the higher densities. However, the latex with 25R2 flocculates and sediments quite rapidly once the CO2 density is lowered to 0.856 g/mL. In contrast, the turbidity of the SAM185-stabilized latex steadily decreases over the entire density range. The turbidity behavior shown in Figure 11 is consistent with the particle sizes obtained using the turbidity ratio method. Whereas the size of the 17R4-stabilized latex particles changed from ∼1.15 to ∼1.39 µm (Table 2), a far larger increase from ∼1.06 to ∼1.74 µm was determined with 25R2. Clearly the 25R2 stabilized latex was much less stable on the basis of the isochoric turbidity profiles.
The initial size of the SAM185-stabilized latex particles was nearly twice the size of of those for Pluronic 17R2 and 25R2. As expected, these larger particles sedimented much faster than those for the other two stabilizers at densities above 0.848 g/mL, leading to a decrease in turbidity. At the lowest density, the Pluronic 17R4 stabilized latex had settled the least, on the basis of on the turbidity. This result is extremely consistent with the smaller particles for Pluronic 17R4 at F ) 0.789 g/mL. Furthermore, the similar behavior in the sedimentation decay curves for SAM185- and Pluronic 25R2-stabilized latexes in Figure 11 at 0.789 g/mL is consistent with the similar particle sizes in Table 2. The same trends in turbidity and particle size were observed with SAM187 (Table 2). An improvement in the latex stability, i.e., a more negative log |dτ/dt|, was observed at the highest CO2 densities for Pluronic 17R4 and 25R2. Although no improvement in the latex stability was observed with SAM185 and 187, flocculation was absent during precipitation, on the basis of visual observation, even for spray times > 25 s. The differences in particle size and stability can be explained by examining the stabilizer molecular architecture and its affinity for the latex interface. When the stabilizers are introduced with the solution phase, they must go to the interface and not get trapped in the interior of the latex particles (if they are to stabilize the latex). The CO2-philic tails must also be sufficiently solvated and long enough to provide steric stabilization. In Table 4,
Stabilized Polymer Microparticles
Figure 10. SEM micrographs of PMMA precipitated by spraying a 1.0 wt % PMMA/THF solution containing 1.0 wt % (A, top) poly(butyl acrylate) (
