Evolution in Structural Polymorphism of Pluronic F127 Poly(ethylene

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Evolution in Structural Polymorphism of Pluronic F127 Poly(ethylene oxide)-Poly(propylene oxide) Block Copolymer in Ternary Systems with Water and Pharmaceutically Acceptable Organic Solvents: From “Glycols” to “Oils”† Rouja Ivanova,‡,§ Bjo¨rn Lindman,‡ and Paschalis Alexandridis*,‡,| Physical Chemistry 1, Center for Chemistry and Chemical Engineering, Lund University, S-221 00 Lund, Sweden, and Department of Chemical Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260-4200 Received March 13, 2000. In Final Form: July 8, 2000 The evolution in the self-assembly of an amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer in ternary systems with water and organic solvents of varying relative polarity is examined. The phase behavior and microstructure of two ternary systems consisting of Pluronic F127 (Poloxamer 407), water, and the pharmaceutically acceptable solvents propylene carbonate (4-methyl-1,3-dioxolan-2-one) or triacetin (glycerol triacetate) are presented. The microstructure of the lyotropic liquid crystalline phases formed and their characteristic length scales are determined from small-angle X-ray scattering (SAXS). The trends in the SAXS lattice spacing and the interfacial area per block copolymer molecule help establish the location of the solvents in the microstructure. The phase behavior of the two systems studied here is discussed in the context of ternary systems of Pluronic F127 with water and polar solvents (“glycols”, e.g., propylene glycol) or apolar organic solvents (“oils”, e.g., xylene). Propylene carbonate and triacetin are shown to have intermediate behavior between that of glycols and oils. The block copolymer structural polymorphism is modulated by the solvent preference to locate in different domains of the block copolymer microstructure.

Introduction Amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers, known as Poloxamers and Pluronics, are commercially available in a variety of molecular weights, PEO/ PPO ratios, and resulting physicochemical properties, and are used in diverse industrial applications.1-13 Of interest to pharmaceutical applications is the ability of PEO-PPO* To whom correspondence should be addressed at The State University of New York. E-mail: [email protected]. † Part of the Special Issue “Colloid Science Matured, Four Colloid Scientists Turn 60 at the Millenium”. ‡ Lund University. § Present address: Technical Physics II/Polymer Physics, Technical University of Ilmenau, D-98684 Ilmenau, Germany. | The State University of New York. (1) Alexandridis, P. Curr. Opin. Colloid Interface Sci. 1997, 2, 478489. (2) Alexandridis, P.; Hatton, T. A. In Polymeric Materials Encyclopedia; Salamone, J. C., Ed.; CRC Press: Boca Raton, FL, 1996; pp 743754. (3) Edens, M. W. Surf. Sci. Ser. 1996, 60, 185-210. (4) Rill, R. L.; Liu, Y.; Ramey, B. A.; VanWinkle, D. H.; Locke, B. R. Chromatographia 1999, 49, S65-S71. (5) Wu, C. H.; Liu, T. B.; Chu, B. J.; Schneider, D. K.; Graziano, V. Macromolecules 1997, 30, 4574-4583. (6) Ivanova, R.; Balinov, B.; Sedev, R.; Exerowa, D. Colloids Surf. A 1999, 149, 23-28. (7) Yang, L.; Alexandridis, P. Controlled Drug Delivery; Park, K., Mrsny, R. J., Eds.; ACS Symposium Series 752; American Chemical Society: Washington, DC, 2000, pp 364-374. (8) Ahmed, F.; Alexandridis, P.; Neelamegham S. Proc. Int. Symp. Controlled Release Bioact. Mater. 2000, 27, 7028. (9) Paavola, A.; Yliruusi, J.; Rosenberg, P. J. Controlled Release 1998, 52, 169-178. (10) Lu, G.; Won Jun, H. Int. J. Pharm. 1998, 160, 1-9. (11) Choi, H.-G.; Lee, M.-K.; Moon-Hee, K.; Kim, C.-K. Int. J. Pharm. 1999, 190, 13-19. (12) Luo, Y.-Z.; Nicholas, C. V.; Attwood, D.; Collett, J. H.; Price, C.; Booth, C.; Chu, B.; Zhou, Z.-K. J. Chem. Soc., Faraday Trans. 1993, 89, 539-546.

PEO block copolymers to form “gels” (lyotropic liquid crystalline structures) in water. In particular, the thermoreversible gelation exhibited by Poloxamers of high PEO content13-17 has been utilized for controlled drug release.7-13 A new application of the Poloxamer gelation properties in water is the separation of biomacromolecules such as DNA or proteins.4,5 In a number of Poloxamer formulations, cosolvents and cosolutes are present. In the presence of selective solvents or cosolvents, PEO-PPOPEO block copolymers can attain a greater variety of microstructures with different functional (e.g., rheological and release) properties. The ternary phase behavior and microstructure of PEOPPO-PEO block copolymers in water, a solvent selective for the hydrophilic PEO blocks, and an apolar solvent (“oil” such as xylene) selective for the relatively hydrophobic PPO block have now been established.18-24 It is (13) Cabana, A.; Ait-Kadi, A.; Juhasz, J. J. Colloid Interface Sci. 1997, 190, 307-312. (14) Chu, B.; Zhou, Z. Surf. Sci. Ser. 1996, 60, 67-143. (15) Wanka, G.; Hoffmann, H.; Ulbricht, W. Macromolecules 1994, 27, 4145-4159. (16) Malmsten, M.; Lindman, B. Macromolecules 1993, 26, 12821286. (17) Schmolka, I. R. J. Am. Oil Chem. Soc. 1991, 68, 206-209. (18) Alexandridis, P.; Olsson, U.; Lindman, B. Macromolecules 1995, 28, 7700-7710. (19) Alexandridis, P.; Zhou, D.; Khan, A. Langmuir 1996, 12, 26902700. (20) Alexandridis, P.; Olsson, U.; Lindman, B. Langmuir 1997, 13, 23-34. (21) Svensson, B.; Alexandridis, P.; Olsson, U. J. Phys. Chem. B 1998, 102, 7541-7548. (22) Alexandridis, P.; Olsson, U.; Lindman B. Langmuir 1998, 14, 4, 2627-2638. (23) Holmqvist, P.; Alexandridis, P.; Lindman, B. Macromolecules 1997, 30, 6788-6797. (24) Holmqvist, P.; Alexandridis, P.; Lindman, B. J. Phys. Chem. B 1998, 102, 1149-1158.

10.1021/la000373d CCC: $19.00 © 2000 American Chemical Society Published on Web 08/26/2000

Block Copolymer Structural Polymorphism

notable that a given PEO-PPO-PEO block copolymer at a constant temperature can attain the whole spectrum of lyotropic liquid crystalline phases with lamellar, hexagonal, and (micellar or bicontinuous) cubic structure, of both oil-in-water (“normal”) or water-in-oil (“reverse”) morphologies18-24 by varying the type and content of the selective solvents (water and oil). Recently we have shown that modulation of PEO-PPO-PEO block copolymer selfassembly can also be achieved by using nonaqueous polar solvents (“glycols”).25,26 Oils such as butyl acetate or xylene, and glycols such as glycerol or ethanol have the ability to modify the block copolymer self-assembly because of their preference to locate in different domains of the microstructure depending on their relative polarity. Oils can reverse the preferred curvature (set by the polymer block PEO/PPO ratio) in the system, whereas glycols affect the preferred curvature to a lesser extent. In this study we are interested in bridging the “gap” between oils and glycols by investigating organic solvents of polarity intermediate to that of oils and glycols. We thus explored the phase behavior and microstructure in ternary systems consisting of a PEO-PPO-PEO block copolymer (Pluronic F127 or Poloxamer 407), water, and propylene carbonate (4-methyl-1,3-dioxolan-2-one) or triacetin (glycerol triacetate). In the Results section, the isothermal ternary phase diagrams and the microstructural characterization [using small-angle X-ray scattering (SAXS)] of the various lyotropic liquid crystalline phases formed are presented. In the Discussion section, the SAXS data are analyzed with respect to the lattice spacing, interfacial area per PEO block, and the location of the solvent in the microstructure. The Pluronic F127-waterpropylene carbonate and Pluronic F127-water-triacetin phase behavior and microstructure data are then discussed in the context of previously studied Pluronic F127 ternary systems so as to demonstrate the evolution of the block copolymer self-assembly by varying the solvent polarity. Materials and Methods Materials. The PEO-PPO-PEO block copolymer, Pluronic F127 (Poloxamer 407), was obtained from BASF Corp. and used as received. Pluronic F127 can be represented as EO100PO70EO100 on the basis of its 12 600 molecular weight and 70 wt % PEO content.27 Propylene carbonate (4-methyl-1,3-dioxolan-2one) (purum) and triacetin (glycerol triacetate) (purum) were purchased from Fluka Chemie, Buchs, Switzerland. Note that all these components are approved for pharmaceutical use and thus our study could have direct impact in pharmaceutical applications. The formulas of Pluronic F127 and the two organic solvents studied are shown in Figure 1. Basic physicochemical parameters of the different solvents considered here are given in Table 1.28-31 Triacetin is a relatively apolar solvent, as revealed by its positive octanol/water partition coefficient. Propylene carbonate is known to exhibit anomalous solvent properties.32,33 It possesses an unusually high dielectric constant and high boiling point. However, it does not show specific intermolecular association as would be expected for solvents with similar properties, (25) Ivanova, R.; Lindman B.; Alexandridis, P. Langmuir 2000, 16, 3660-3675. (26) Alexandridis, P.; Ivanova, R.; Lindman B. Langmuir 2000, 16, 3676-3689. (27) Pluronic and Tetronic Block Copolymer Surfactants, Technical Brochure, BASF Corp., 1989. (28) Handbook of Chemistry and Physics; Lide, D. R., Ed.; CRC Press: Boca Raton, FL, 1994. (29) McClellan, A. L. Tables of Experimental Dipole Moments; Rahara Enterprises: El Cerrito, CA, 1974. (30) Leo, A.; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525-616. (31) Hansen, Ch. in Handbook of Surface and Colloid Chemistry; Birdi, K. S., Ed.; CRC Press: New York, 1997; Ch. 10. (32) Simeral, L.; Amey, R. L. J. Phys. Chem. 1970, 74, 1443-1446. (33) Payne, R.; Theodorou, I. E. J. Phys. Chem. 1972, 76, 28922900.

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Figure 1. Chemical structure of the Pluronic F127 block copolymer and the organic solvents examined in this study. for example, water and N-monoalkyl amides.33 Its high dielectric constant is rather thought to be due to its large dipole moment only. Propylene carbonate has limited solubility in water at 25 °C.34 No experimental data for the octanol/water partition coefficient of propylene carbonate were found. The octanol/water partition coefficient log P is related to the solvent molal solubility in water S and an estimation can be made using the empirical equation:35

log

1 ) a log P + b S

(1)

where a ) 1.214 ( 0.05 and b ) -0.85 ( 0.11 are empirical constants. The solubility of propylene carbonate and triacetin in water is about 21 and 8 wt % respectively. The estimated values of log P for propylene carbonate and triacetin are given in the relevant column in Table 1 in brackets. The positive value of 0.4 indicates that propylene carbonate partitions preferably in the octanol phase. The estimated log P value for triacetin of 1.0 is higher than that for propylene carbonate, which indicates that triacetin is relatively more apolar. Note that the octanol/water partition coefficients of propylene carbonate and triacetin are much lower than that of xylene. In fact, the propylene carbonate and triacetin log P values are comparable to that of butanol. Determination of Phase Diagrams. Samples of various compositions covering the entire ternary phase diagram of the systems studied were prepared by weighing the appropriate amounts of block copolymer, Millipore-purified water, and propylene carbonate or triacetin into 8-mm (i.d.) glass tubes. Care has been taken during sample preparation to minimize the exposure of propylene carbonate and triacetin to atmospheric humidity. The samples were flame-sealed immediately after preparation, centrifuged several times over several days in alternating directions to facilitate mixing, and left for equilibration at 25 ( 0.5 °C. More samples were prepared in the vicinity of the phase boundaries where necessary to accurately determine them. During the equilibration period the samples were monitored for birefringence and possible changes in the structure by inspection under polarized light. The equilibration was considered complete in about six weeks. Previous experience has shown that this period is sufficient for reaching an equilibrium in similar copolymer systems that do not impose diffusion limitations.25,36 Visual inspection under polarized light distinguished between one-phase regions with different microstructures and multiplephase regions. The one-phase samples are macroscopically homogeneous, clear and transparent, whereas the multiple-phase samples are either homogeneous but not clear, or macroscopically heterogeneous and phase-separated. The samples in the solution, micellar cubic and bicontinuous cubic liquid crystalline phases are optically isotropic (nonbirefringent), whereas those in the hexagonal and lamellar liquid crystalline phase, are anisotropic (34) Catherall, N.; Williamson, A. J. Chem. Eng. Data 1971, 16, 335336. (35) Hansch, C.; Quinlan, J.; Lawrence, G. J. Org. Chem. 1968, 33, 347-350. (36) Ivanova, R.; Lindman B.; Alexandridis, P. J. Colloid Interface Sci., in press.

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Table 1. Physicochemical Parameters of Solvents Examined in This Study

solvent

MW

mp °C

bp °C

densitya (g/cm3)

water propylene glycol propylene carbonate 1-butanol triacetin p-xylene

18.01 76.10 102.09 74.12 218.21 106.17

0 -60 -49 -90 -78 13

100 188 242 117 259 138

0.9982 1.0327 1.1990 0.8061 1.1580 0.8577

dielectric constanta

dipole momentb

78.5 32.0 65.1 17.1

3.11

2.2

4.94 3.00 2.37 0.10

log Pc

solubility parameterd (MPa1/2) 47.8 30.2 27.2 23.3

-1.41 (0.4 ( 0.1) 0.88 0.25 (1.0 ( 0.1) 3.15

a

17.9 b

MW: molecular weight; mp, melting point; bp, boiling point; log P: logarithm of the octanol/water partition coefficient. The density, the dielectric constant and dipole moments (in debye units) of solvents are given at 25 °C. c The data are taken froma refs 28;b 29;c 30;d 31.

(birefringent). AXS measurements on selected samples were used to verify the phase boundaries. Structural Characterization Using SAXS. SAXS diffraction patterns were recorded using a Kratky compact small-angle system equipped with a position-sensitive detector (OED 50M, Mbraun, Graz, Austria).25 The microstructure of the liquid crystalline phases was determined by the relative positions of the Bragg diffraction peaks evaluated from the desmeared37 spectra. For lamellar and hexagonal structures the relative positions of the peaks should obey, respectively, the relations 1:2:3... and 1:x3:2:x7:3 .... The lattice parameter in the lamellar structure, d, and the distance between the planes defined by the centers of two adjacent rows of cylinders in the hexagonal structure, d, both referred to as lattice spacing, were determined from the position q* of the first and most intense diffraction peak:

d)

2π q*

(2)

The average area, ap, that a PEO block of the triblock copolymer occupies at the interface between the PEO-rich and the PPOrich domains of the microstructure can be calculated from the lattice spacing and (a) the volume fraction of the components that constitute the interfacial region, Φint, and (b) the volume fraction of the PPO-rich domains, f. In the lamellar structure the calculation of ap involves only Φint, whereas in the hexagonal structure it involves both Φint and f. The polar PEO-rich microdomains consist of the PEO blocks and water, and the relatively more apolar PPO-rich microdomains consist of the PPO blocks and possibly apolar organic solvent. The organic solvents partition or participate in these microdomains depending on their relative polarities. Obviously, the block copolymer creates the interface between the PEO-rich and the PPO-rich domains and thus constitutes a major part of Φint. A solvent that acts as a cosurfactant would also contribute to Φint. The definition of these two parameters for a particular block copolymer-solvent combination will be discussed in detail in the Discussion section. In general, the following relations can be considered:

Φint ) Φp + xΦs

(3)

f ) 0.34Φp + yΦs

(4)

and

where Φp is the volume fraction of the block copolymer in the ternary system and Φs is the volume fraction of the organic solvent; 0.34 is the volume fraction of the PPO block in the Pluronic F127 macromolecule (PPO weight fraction ) 0.30). To convert the weight fractions of the components into volume fractions, the bulk densities of the copolymer (1.05 g/cm3), water, and solvents (given in Table 1) are used. In eq 3 x denotes the fraction of the solvent that contributes to the formation of the interfacial region, whereas y in eq 4 is the fraction of the solvent that is located in the PPO-rich domains. The values of x and y vary from 0 to 1 depending on the properties of the given organic solvent. Different sets of x and y can result in dramatic variations (37) Singh, M.; Ghosh, S.; Shannon, R. J. Appl. Crystallogr. 1993, 26, 787.

in the values of the interfacial area. The interfacial area per PEO block can be calculated from:18,20

lamellar: ap )

νp dΦint

hexagonal: ap )

( )

νp πx3 f dΦint 2

1/2

(5)

where υp ≈ 20 000 Å3 is the volume of one Pluronic F127 macromolecule. The establishment of the crystallographic space group of the cubic liquid crystalline phases is more complex than those of the lamellar and hexagonal structures and not always unambiguous. An agreement between the interfacial area calculated in the different microstructures of the phase diagram is usually very useful to confirm the indexing of the cubic lattice.21,25,38 A detailed description of the indexing of the cubic lattice, the calculation of the lattice parameter, and the interfacial area in the cubic (micellar and bicontinuous) liquid crystalline phases can be found in ref 25.

Results PluronicF127-Water-PropyleneCarbonatePhase Diagram: Overview, Structural Characterization, and SAXS Lattice Spacing Trends. Four one-phase regions were identified in the ternary phase diagram of Pluronic F127 in the presence of water and propylene carbonate (Figure 2, top). Starting from the water corner of the phase diagram the following phases appear in counterclockwise direction: isotropic water-rich solution (L1), normal (oil-in-water) micellar cubic (I1) and normal hexagonal (H1) lyotropic liquid crystalline phases, and isotropic water-lean solution (L2). The two- and threephase regions were not examined in detail and the study focused on the one-phase liquid crystalline regions. The values of the SAXS lattice spacing measured in the hexagonal phase are reported in Figure 2 at the corresponding compositions in the phase diagram. Analysis of the lattice spacing data measured at various compositions, the calculation of the area per PEO block, and the information extracted for the location of the solvent in the microstructure will be presented in the Discussion section. Water-Rich (L1) and Water-Lean (L2) Solution Phases. The isotropic water-rich solution extends from the water corner of the phase diagram up to 17 wt % Pluronic F127 along the copolymer-water axis and up to 21 wt % propylene carbonate along the water-propylene carbonate axis. PEO-PPO-PEO block copolymers are wellknown to form micelles in water39-46 and in water(38) Alexandridis, P. Macromolecules 1998, 31, 6935-6942. (39) Alexandridis, P.; Spontak, R. J. Curr. Opin. Colloid Interface Sci. 1999, 4, 130-139. (40) Alexandridis, P.; Holzwarth, J. F. Langmuir 1997, 13, 60746082. (41) Jo¨rgensen, E.; Hvidt, S.; Brown, W.; Schille´n, K. Macromolecules 1997, 30, 2355-2364. (42) Exerowa, D.; Sedev, R.; Ivanova, R.; Kolarov, T.; Thadros, Th. F. Colloids Surf. A 1997, 123-124, 277-282. (43) Alexandridis, P.; Athanassiou, V.; Hatton, T. A. Langmuir 1995, 11, 2442-2450.


Figure 2. Isothermal (25 °C) phase diagrams of the ternary systems (top) Pluronic F127-water-propylene carbonate, and (bottom) Pluronic F127-water-triacetin. The composition is given in weight fractions. The boundaries of the one-phase regions are drawn with solid lines. L1 denotes the ternary composition region of isotropic water-rich solution. I1 denotes the region of normal micellar cubic (lyotropic liquid crystalline) microstructure, H1 the normal hexagonal microstructure, V1 the normal bicontinuous cubic microstructure, and LR the lamellar microstructure. L2 denotes the region of isotropic waterlean solution. The samples whose composition falls outside the L1, I1, H1, V1, LR, and L2 regions are two- or three-phase. The values (in Å) of the SAXS lattice spacing obtained in the lyotropic liquid crystalline microstructures are shown at the corresponding compositions in the phase diagram.

cosolvent mixtures.47 Although we have not examined the micellization process of Pluronic F127 in the presence of water and propylene carbonate, the occurrence of the neighboring micellar cubic liquid crystalline phase indicates micelle formation in the L1 phase. Propylene carbonate has limited solubility in water and leads to the (44) Bahadur, P.; Pandya, K.; Almgren, M.; Li, P.; Stilbs, P. Colloid Polym. Sci. 1993, 271, 657-667. (45) Wanka, G.; Hoffmann, H.; Ulbricht, W. Colloid Polym. Sci. 1990, 268, 101-117. (46) Alexandridis, P.; Andersson, K. J. Colloid Interface Sci. 1997, 194, 166-173. (47) Alexandridis, P.; Yang, L. Langmuir 2000, 16, 4819-4829.

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appearance of a second (water-lean) solution region in the phase diagram. Propylene carbonate can dissolve only about 7.5 wt % water and about 10 wt % Pluronic F127. The L2 region however, extends down from the propylene carbonate corner of the phase diagram up to as much as 35 wt % water and 50 wt % Pluronic F127. At such water and block copolymer contents, much higher than their mutual solubility with propylene carbonate, the system can form an equilibrium clear solution only in the case where the polar and apolar domains are separated by the block copolymer because of, for example, formation of reverse micelles. Normal Micellar Cubic Liquid Crystalline Phase (I1). A normal micellar cubic phase is identified over a broad concentration range (18-64 wt % Pluronic F127) along the copolymer-water axis, and can accommodate up to 25 wt % propylene carbonate. The micellar cubic phase consists of discrete micelles crystallized in a cubic lattice. SAXS diffraction patterns from samples at 30 wt % Pluronic F127 are presented in Figure 3a. The intensity was low and only few Bragg peaks could be identified. This imposed difficulties in the assignment of the cubic lattice to one of the many possible crystallographic space groups.48,49 We have tested several possible indexations of the recorded SAXS diffraction patterns to the most commonly observed crystallographic space groups in similar systems20-22,26 by plotting the reciprocal dhkl spacing versus the sum of the Miller indices (h2 + k2 + l2)1/2 (plots are not shown). The main criteria used in resolving the crystallographic space group were values of the interfacial area per PEO block that were close to the corresponding values in the neighboring microstructures and consistency of the lattice parameter and interfacial area with the trends observed over the entire phase diagram; the association number of the micelles was also taken into consideration. For a correct assignment the plot of dhkl versus (h2 + k2 + l2)1/2 passes through the origin, and the lattice parameter, R, is given by the slope of the plot. The interfacial area per PEO block, ap, and the association number of the micelles, Nassoc, were calculated using eqs 2 and 4 from ref 25 assuming that the entire propylene carbonate amount contributes to the formation of the interface together with the block copolymer, and that 20% of it participates in the PPO-rich domains, that is, x ) 0.2 in eq 3 and y ) 1 in eq 4 (see Discussion section). The SAXS diffraction pattern for a sample with composition 30 wt % Pluronic F127 and 70 wt % water shown in Figure 3a was indexed to body-centered (I...) cubic lattice. Values of R ) 208 Å, ap ) 215 Å2, and Nassoc ) 65 were thus obtained. A body-centered cubic structure had been found earlier in the binary Pluronic F127-water system in small-angle neutron scattering studies of shearoriented samples.50,51 The cubic lattices of samples with ternary Pluronic F127-water-propylene carbonate compositions, however, have been assigned to primitive (P...) structure. The corresponding values of their characteristic parameters are R ) 149 Å, ap ) 205 Å2, and Nassoc ) 63 for composition of 30 wt % Pluronic F127, 60 wt % water, and 10 wt % propylene carbonate, and R ) 141 Å, ap ) 192 Å2, and Nassoc ) 67 for composition of 30 wt % Pluronic F127, 50 wt % water, and 20 wt % propylene carbonate. The micellar cubic structure obtained in the ternary Pluronic F127-water-butanol system has also been (48) Fontell, K. Colloid Polym. Sci. 1990, 268, 264-285. (49) Mariani, P.; Luzzati, V.; Delacroix, H. J. Mol. Biol. 1988, 204, 165-189. (50) Holmqvist, P.; Alexandridis, P.; Lindman, B. Langmuir 1997, 13, 2471-2479. (51) Mortensen, K. J. Phys. Condens. Matter 1996, 8, A103-A124

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Figure 3. SAXS diffraction patterns obtained in various microstructures in the Pluronic F127-water-propylene carbonate system: (a) micellar cubic microstructure, I1, at 30 wt % copolymer content; (b) hexagonal microstructure, H1, at 65 wt % copolymer content (the propylene carbonate content is indicated above the corresponding curves); and (c) hexagonal microstructure, H1, a sample with composition 30 wt % Pluronic F127, 35 wt % water, and 35 wt % propylene carbonate. The identified Bragg peaks in the SAXS spectra are marked by arrows. The Miller indices (hkl) to which the diffraction peaks in the SAXS spectra from the I1 microstructure are indexed are indicated. The diffraction patterns are shifted vertically where necessary to avoid overlap. The relative diffraction peak intensities in the hexagonal structure are comparable because the spectra were recorded under the same conditions.

indexed to a primitive cubic lattice.52 The transition from body-centered to primitive cubic lattice has not been investigated further. Normal Hexagonal Liquid Crystalline Phase (H1). A normal hexagonal phase, with microstructure consisting (52) Mortensen, K.; Talmon, Y. Macromolecules 1995, 28, 8829.

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of cylindrical assemblies packed in a hexagonal lattice, has been obtained at high copolymer content (66-75 wt %) along the copolymer-water axis. It can accommodate up to 35 wt % propylene carbonate and swells to lower copolymer content with increasing propylene carbonate content (this swelling is reflected to a bend in the phase boundaries of the H1 region toward the water-propylene carbonate axis). SAXS diffraction patterns obtained for samples at 65 wt % copolymer concentration are shown in Figure 3b. Four to six Bragg diffraction peaks with relative positions that follow the sequence 1:x3:2:x7... are registered in each SAXS pattern, confirming the hexagonal structure. A shift of the peaks toward higher q values with increasing propylene carbonate content (at constant copolymer content), corresponding to a decrease of the lattice spacing, is observed. This trend is observed through the entire H1 region (as seen in Figure 2) and will be further analyzed in the Discussion. The extent of the H1 region to as low as 22 wt % Pluronic F127 at 30-35 wt % propylene carbonate is notable. The samples in the H1 region are clear stiff birefringent gels, but their viscosity is decreasing at lower copolymer content, and those in the shaded area shown in Figure 2 exhibit peculiar shearing behavior. Even a small mechanical disturbance causes loss of the hexagonal structure and transformation into nonbirefringent liquid. After being left to relax, they attain again the hexagonal structure. A SAXS diffraction pattern from a sample in the shaded area proving its hexagonal structure is shown in Figure 3c. Pluronic F127-Water-Triacetin Phase Diagram: Overview, Structural Characterization, and SAXS Lattice Spacing Trends. The ternary Pluronic F127water-triacetin system (Figure 2, bottom) offers a richer phase behavior than the propylene carbonate system: two isotropic solution phases, a water-rich (L1) and a waterlean (L2), and four lyotropic liquid crystalline phases, normal micellar cubic (I1), normal hexagonal (H1), normal bicontinuous cubic (V1), and lamellar (LR) are observed. The values of the SAXS lattice spacing obtained in the hexagonal and lamellar liquid crystalline phases are recorded at the corresponding compositions in the phase diagram. Water-Rich (L1) and Water-Lean (L2) Solution Phases. Triacetin exhibits a miscibility gap with water much broader than propylene carbonate. Triacetin 8 wt % is soluble in water and up to 4 wt % water is soluble in triacetin. Therefore, both L1 and L2 solution phases appear in a more limited range than in the case of propylene carbonate. It is notable, however, that the extent of the L2 region from the triacetin corner of the phase diagram up to 35 wt % water and 55 wt % Pluronic F127 is comparable to that in the propylene carbonate system. The presence of micelles in the two solution phases can be rationalized with similar arguments as presented in the case of propylene carbonate. The very narrow range of water/copolymer ratios in which the water-lean solution appears is notable. The boundary of L2 at higher copolymer content coincides with a dilution line of constant water/ copolymer ratio of 0.5 water molecules per EO monomer unit. This value reflects the minimum amount of hydration water necessary to induce reverse micelle formation.46 Normal Micellar Cubic Liquid Crystalline Phase (I1). The normal micellar cubic phase identified at 18 to 64 wt % Pluronic F127 along the copolymer-water axis can accommodate up to 11 wt % triacetin. The assignment of the cubic lattice has been assessed in the same way as in the system of propylene carbonate. A SAXS diffraction pattern of a sample with composition 30 wt % Pluronic F127, 65 wt % water, and 5 wt % triacetin is shown in


Figure 4a. The cubic lattice was assigned to primitive (P...) structure, as in the case of propylene carbonate. Values of R ) 168 Å, ap ) 194 Å2, and Nassoc ) 79 were estimated for its characteristic parameters. Normal Hexagonal Liquid Crystalline Phase (H1). The normal hexagonal phase attained by the copolymer at 66 to 75 wt % Pluronic F127 content along the copolymer-water axis can accommodate only up to 15 wt % triacetin. The SAXS diffraction patterns for samples at 65 wt % Pluronic F127 shown in Figure 4b exhibit four to six Bragg diffraction peaks that follow the sequence 1:x3:2:x7... and confirm the hexagonal structure. In the triacetin system (similarly to propylene carbonate), a shift is observed toward higher q values of the SAXS diffraction patterns corresponding to a decrease of the lattice spacing with increasing triacetin content. Again, this trend is preserved through the entire H1 region (see Figure 2 and the Discussion section). Normal Bicontinuous Cubic Liquid Crystalline Phase (V1). A normal bicontinuous cubic phase (V1) is obtained in a very narrow composition region, 53 to 57 wt % Pluronic F127 and 19 to 22 wt % triacetin. V1 is a microstructure rarely observed.22,25 The bicontinuous cubic phases have intricate microstructure that can be represented as interconnected (bicontinuous) cylindrical micelles arranged in a cubic lattice. An alternative representation is that of interconnected bilayers arranged in a cubic lattice. Both representations are commonly used to describe the V1 microstructure and can converge topologically. A SAXS diffraction pattern of a V1 sample is shown in Figure 4c. The most common crystallographic space group observed for the bicontinuous cubic phases formed in PEO-PPO-PEO block copolymer systems18,22,25 as well as in surfactant and lipid systems48,49 is Ia3d. Two specific Bragg peaks are characteristic of Ia3d: The first and most intense at Miller indices hkl ) 211, and a “shoulder” at hkl ) 220. The first two Bragg peaks in the diffraction pattern indeed were indexed as 211 and 220. Several higher-order diffraction peaks (some with very low intensities) support this indexation judging from the linearity and the (0,0) intercept of the plots of the reciprocal dhkl spacing versus the sum of the Miller indices (h2 + k2 + l2)1/2 (not shown). A value of 357 Å is obtained for the lattice parameter, determined by the slope of the dhkl versus (h2 + k2 + l2)1/2 plot. The interfacial area per PEO block was calculated using eqs 5 and 6 from ref 25. Assuming that x ) 0.2 in eq 3 and y ) 1 in eq 4, which is equivalent to the assumption that the entire triacetin amount contributes to the formation of the interface together with the block copolymer, and 20% of it participates in the PPO-rich domains (see the Discussion section), a value of 159 Å2 is obtained. This value is close to the values of the interfacial area (obtained under the same assumption for the location of the solvent) in the neighboring hexagonal and lamellar phases, which supports the assignment of the bicontinuous cubic structure to the Ia3d space group. Lamellar Liquid Crystalline Phase (Lr). A lamellar phase, with microstructure consisting of planar assemblies (lamellae), has been obtained between 35 and 55 wt % Pluronic F127 content and higher triacetin content, 25 to 48 wt %. LR does not form along the copolymer-water axis because the Pluronic F127 macromolecule is asymmetric, having much larger PEO blocks than PPO block, and the preferred curvature in the binary Pluronic F127water system is positive. The SAXS diffraction patterns obtained for samples at 45 wt % copolymer concentration are shown in Figure 4d. Two Bragg diffraction peaks can be clearly distinguished in each SAXS pattern. Their

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Figure 4. SAXS diffraction patterns obtained in various microstructures in the system Pluronic F127-water-triacetin: (a) micellar cubic microstructure, I1, at 30 wt % copolymer content; (b) hexagonal microstructure, H1, at 65 wt % copolymer content; (c) bicontinuous cubic microstructure, V1, a sample with composition of 55 wt % Pluronic F127, 25 wt % water, and 20 wt % triacetin; and (d) lamellar microstructure, LR, at 45 wt % copolymer content. The triacetin content is indicated above the corresponding curves. The identified Bragg peaks in the SAXS spectra are marked by arrows. The Miller indices (hkl) to which the diffraction peaks in the SAXS spectra from the I1 and V1 microstructures are indexed are indicated. The diffraction patterns are shifted vertically where necessary to avoid overlap. The relative diffraction peak intensities in the hexagonal and lamellar structure are comparable because the spectra were recorded under the same conditions.

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positions relate as 1:2 and indicate the lamellar structure. The shift to higher q values of the SAXS spectra, corresponding to lower lattice spacing with increasing the triacetin content, is also observed through the lamellar structure (see Figures 4d and 2). Discussion A. SAXS Lattice Spacing Trends with Varying Water-Organic Solvent Content. To understand the role of the solvents in the self-assembly of PEO-PPO-PEO block copolymers it is necessary to examine not only the macroscopic phase behavior but also the trends in the characteristic length scales in the different microstructures.23,24,26,36 Systematic SAXS measurements were performed on a series of samples in the liquid crystalline phases of the ternary Pluronic F127-water-propylene carbonate and Pluronic F127-water-triacetin systems. The lattice spacing for each sample in the hexagonal and lamellar structures (values are shown in Figure 2) was obtained directly (with no assumptions involved) from the relative position of the first peak of the SAXS diffraction patterns using eq 2. The lattice spacing decreases both with increasing the copolymer content at constant solvent content and with increasing the propylene carbonate or triacetin content at constant copolymer content. The first trend is commonly observed and originates from an increase in the total amount of interface for a given volume. The second trend is specific to the solvent effects26,36 and results from the preference of the different solvents (depending on their relative polarity) to locate in different parts of the microstructure. The effects of propylene carbonate and triacetin on the lattice spacing expressed as percentage variations of the lattice spacing in the hexagonal structure at two copolymer concentrations are shown in Figure 5. This presentation of the SAXS data reveals that within the same microstructure and at constant copolymer content the lattice spacing can decrease (compared with that in water) by no more than about 20% in the presence of propylene carbonate or triacetin. Similarly, the lattice spacing has been found to vary by no more than (20% in the presence of glycols.26 These limits within which the lattice spacing can vary while preserving the same microstructure reveal the extent to which the block copolymer macromolecule can deform under external stresses imposed by changes in the solvent conditions and appear to be common for various solvents. In particular, the way propylene carbonate and triacetin affect the lattice spacing is similar to that of ethanol26 or butanol.23 It has been shown23 that butanol is located in the PPO-rich domains but participates in the formation of the interface together with the block copolymer. The similarity in the influence of these solvents indicates that propylene carbonate and triacetin are located in the PPO-rich domains of the liquid crystalline microstructures. This conclusion is supported by the macroscopic phase behavior of Pluronic F127-waterpropylene carbonate and Pluronic F127-water-triacetin systems (Figure 2) as compared with that of butanol.23 Propylene carbonate and triacetin are immiscible with water and induce formation of structures with less positive or zero curvature, that is, decrease the preferred curvature by swelling the PPO block. The location of propylene carbonate and triacetin in the microstructure was estimated by analysis of the trends in the interfacial area per PEO block calculated on the basis of SAXS lattice spacing data. B. Interfacial Area per PEO Block and Location of Propylene Carbonate and Triacetine in Microstructure. The variations in the lattice spacing shown in

Figure 5. Percent variation of the lattice spacing at different organic solvent contents with respect to that in the absence of organic solvent plotted versus the percent volume fraction of the organic solvent in the solvent + water mixture. Data in the hexagonal structure at constant copolymer content (65 and 55 wt % Pluronic F127) for both propylene carbonate (circles) and triacetin (squares) are shown on the same graph. The absolute values of the lattice spacing are shown at the corresponding compositions in the phase diagrams in Figure 2.

Figure 5 and discussed in section A can be related to changes in the interfacial area that one Pluronic F127 macromolecule occupies at the interface between the PEOrich and the PPO-rich domains. To calculate the interfacial area per PEO block in the lamellar structure, the interfacial volume fraction (Φint) has to be determined in addition to the lattice spacing. In the hexagonal structure this calculation involves also the volume fraction of the PPO-rich domains (f). The determination of these parameters is usually connected to an assumption for the location of the organic solvents in the PEO-rich or the PPO-rich domains of the microstructure. The trends in the interfacial area calculated within a given assumption on the solvent distribution can be used as a criterion to establish the microdomains in which the solvents are located.23,26 The interfacial area has been shown to remain almost constant (within (10%) for many systems of PEOPPO-PEO block copolymers with water and xylene, solvents that are clearly located in the PEO-rich and the PPO-rich microdomains respectively.21-23 Invariance of the interfacial area has been found as well in systems of nonionic surfactants containing poly(ethylene oxide).53 Hence, self-consistence and invariance of the values of


the interfacial area in the liquid crystalline structures over the entire phase diagram were sought. Several locations of propylene carbonate and triacetin in the different microdomains were tested to obtain relatively constant interfacial areas. As discussed in the previous section, the influence of propylene carbonate and triacetin on the lattice spacing and their overall phase behavior are similar to those of solvents of intermediate polarity such as butanol. Therefore, it is not reasonable to consider that propylene carbonate or triacetin are located in the PEO-rich domains. We thus assumed initially that the entire amount of propylene carbonate or triacetin is located in the PPO-rich domains (y ) 1 in eq 4: f ) 0.34Φp + Φs) and only the block copolymer participates in the formation of the interface (i.e., x ) 0 in eq 3: Φint ) Φp). The ap values obtained within this assumption at three copolymer concentrations (65, 55, and 45 wt % Pluronic F127) in the hexagonal, lamellar, and bicontinuous cubic liquid crystalline structures are shown with filled symbols in Figure 6. Although the interfacial area is expected21-23 to be invariable, Figure 6 shows that the area per PEO block changes significantly (compared with that at the binary Pluronic F127-water compositions) with increasing the volume fraction of the organic solvent in the solvent + water mixture. Hence, the assumption made above that all solvent is located in the PPO-rich domains is not correct and needs to be revised. Unreasonably large changes in the interfacial area have been found previously in the case of butanol if butanol was assumed to locate entirely in the PPO-rich domains.23 We have tested also the assumption that all the (propylene carbonate or triacetin) solvent is located at the interface, that is, x ) 1 in eq 3 and y ) 0 in eq 4. However, this is not a feasible location because it resulted in values of the interfacial area per PEO block decreasing unreasonably with varying water/ solvent ratio (data are not shown). It has been then shown23 by probing different locations for butanol (varying x and y in eqs 3 and 4 respectively) that the whole amount of butanol participates in the formation of the interface together with the block copolymer and about 20% of butanol contributes to the PPOrich microdomains. To calculate the interfacial area per PEO block in the Pluronic F127-water-propylene carbonate and Pluronic F127-water-triacetin systems, we have tested the same assumption (i.e., x ) 1 in eq 3, leading to Φint ) Φp + Φs, and y ) 0.2 in eq 4, leading to f ) 0.34Φp + 0.2Φs). The results obtained within this assumption are shown with open symbols in Figure 6. The values previously determined for butanol are indicated in the figure with lines. The invariance of the interfacial area and the good agreement between the values calculated at constant copolymer content in different microstructures are strong evidence that the above assumption is correct, that is, propylene carbonate and triacetin (similarly to butanol) are located at the interface between the PEOrich and the PPO-rich domains and about 20% of the solvent amount participates in the PPO-rich domains of the microstructure. The microstructural information for the location of propylene carbonate and triacetin at the interface between the PEO-rich and the PPO-rich microdomains carries implications on their macroscopic phase behavior with respect to the inability of these solvents to form reverse structures, as discussed below. C. Evolution of Microstructure in PEO-PPO-PEO Block Copolymer-Water-Organic Solvent Ternary Systems: from Glycols to Oils. Both the macroscopic (53) Olsson, U.; Wennerstro¨m, H. Adv. Colloid Interface. Sci. 1994, 49, 113.

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Figure 6. Interfacial area per PEO block in various microstructures and at various block copolymer contents (65, 55, and 45 wt % Pluronic F127) plotted as a function of the percent volume fraction of the organic solvent in the solvent + water mixture. Data for propylene carbonate (circles) and triacetin (squares) are shown on the same graph. The open and filled symbols refer to different assumptions for the locations of the organic solvents in the microstructure. The filled symbols correspond to an assumption that the entire amount of the organic solvent is located in the PPO-rich microdomains. The open symbols correspond to an assumption that the entire amount of the organic solvent is located at the interface and 20% of the solvent contributes to the PPO-rich microdomains. The lines denote the values of the interfacial area for butanol calculated under the latter assumption. The calculation of the interfacial area is discussed in detail in the text.

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changes in the phase boundaries and the microscopic trends in the SAXS lattice spacing reflect changes in the preferred curvature of the system. Solvents have different preferences to locate in different microdomains, depending on their physicochemical parameters, and in this way will affect the preferred curvature of the system.23,26 The phase behavior of PEO-PPO-PEO block copolymers is initially determined by the ratio of the hydrophilic PEO blocks to the relatively hydrophobic PPO block. By adding solvents that distribute between the PEO and the PPO domains, the preferred curvature is modified and the resulting phase behavior depends on the relative volume ratio of the PEOrich domains, consisting of the PEO blocks of the copolymer and their selective solvent, to the PPO-rich domains, consisting of the PPO block of the copolymer PPO and its selective solvent. Water, a solvent selective for PEO, swells the PEO blocks and induces formation of structures with higher (positive) preferred curvature (oil-in-water) with increasing water content. This tendency can be seen in Figure 2 by following the progression of the microstructure at the binary Pluronic F127-water axis. Solvents that are selective for the PPO block swell it preferably and induce formation of structures with less positive or negative curvature (water-in-oil). This tendency can be seen in Figure 2 by following the progression of the microstructure along dilution lines originating from the propylene carbonate or triacetin corner. The latter is also illustrated by the series of Pluronic F127-water-organic solvent phase diagrams shown in Figure 7 (see particularly the Pluronic F127-water-xylene system). The phase behavior in representative PEO-PPO-PEO block copolymer - solvent systems is shown in Figure 7. The layout of this figure indicates the evolution of the microstructure attained by PEO-PPO-PEO block copolymers in ternary systems with water and an organic solvent, by proceeding from a polar solvent (“glycol”) such as propylene glycol, through solvents of intermediate polarity such as propylene carbonate, butanol, or triacetin, to an apolar solvent (“oil”) such as xylene. The octanol/water partition coefficient of glycols is negative, for example, for propylene glycol log P ) -1.41, whereas that of oils is highly positive, for xylene log P ) 3.15 (see Table 1). The octanol/water partition coefficient of propylene carbonate, triacetin, or butanol is in the order of 1, which is significantly different from that of both glycols and oils. The comparison of these phase diagrams clearly shows the different action of the glycols and oils. Glycols are polar solvents that have the ability to maintain the stability of one and the same microstructure up to very high glycol/water ratios. Some water-soluble glycols can have a relative preference to locate in the PPO-rich domains. In asymmetric macromolecules with large PEO blocks such as Pluronic F127, glycols are not able to induce the development of reverse structures (with negative curvatures), irrespective of the glycol location in the microstructure.36 Oils are apolar solvents that, in contrast to glycols, show a distinctive tendency to promote the formation of a larger variety of microstructures. Oils are immiscible with water and segregate from it by locating in the PPO-rich domains. At sufficiently high oil/water ratios the preferred curvature of the system passes through zero and the formation of reverse phases is favored. Solvents such as propylene carbonate, butanol, and triacetin have intermediate behavior. They form a larger variety of microstructures than glycols such as propylene glycol, and fewer microstructures but over larger stability regions than the apolar oils such as xylene. These solvents are still partly located in the PPO-rich domains but are

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mainly active by increasing the total interfacial area, that is, act as cosurfactants (see section B). The ability of the different solvents to modify the preferred curvature in the block copolymer systems (revealed by the series of ternary phase diagrams shown in Figure 7) is presented in a more explicit way in Figure 8. The extent of the lyotropic liquid crystalline phases at two sections of the ternary phase diagrams, at 25 and at 53 wt % Pluronic F127, is redrawn with respect to the organic solvent volume fraction in the solvent + water mixture. This presentation helps to compare the influence of the different solvents with respect to their effect on the preferred curvature. Figure 8 shows that starting from xylene and moving down to propylene glycol, higher and higher volume fractions of the organic solvent are necessary to induce transition from normal micellar cubic to normal hexagonal structure, that is, to decrease the preferred curvature. In other words, in this sequence, the solvents become less capable of promoting new structures with less positive or negative preferred curvature. This is evidence that less and less amount of the solvent locates in the PPO-rich domains. The point of zero curvature, where the volume of the PPO-rich and the PEO-rich domains are equal (f ) 0.5), was calculated for the case of xylene and is marked in Figure 8 by an arrow. Higher volume fractions of the solvent would be necessary to reach this point in the cases of solvents other than xylene. This can be represented by moving the point of zero curvature to higher Φsolvent/(Φsolvent + Φwater) values. This change is so effective that already triacetin is not able to promote reverse structures, and for propylene carbonate and propylene glycol the point of zero curvature cannot be reached even in the absence of water. A conclusion that, starting from xylene and moving to propylene glycol, the solvent amount in the PPO-rich domains decreases, hence the solvent amount at the interface increases, can be made on the basis of the trends in the boundaries of the liquid crystalline phases, as shown in Figure 8. This agrees very well with the location of propylene carbonate and triacetin obtained from the analysis of the trends in the interfacial area calculated on the basis of the SAXS experiments (see Figure 6). D. Solvent Properties of Propylene Carbonate. With respect to both macroscopic changes in the phase diagram and microscopic changes in the lattice spacing, propylene carbonate has similar behavior to butanol and triacetin, which have intermediate polarity between that of the polar glycols and the apolar oils. However, propylene carbonate is a polar solvent, as evident from its high dielectric constant and dipole moment (Table 1). On the contrary, the estimated value of 0.4 for the octanol/water partition coefficient given in Table 1 shows that propylene carbonate partitions preferably in the octanol phase. As noted in the materials section, propylene carbonate exhibits anomalous properties, for example, being highly polar and having limited miscibility with water at the same time. Its unusually high dielectric constant is due to its large dipole moment rather than to specific intermolecular association.33 The hypothesis we have developed to rationalize the different behavior of the polar solvents and the preferences of some glycols to locate in the PPOrich domains is based on a simple classification of solvents as PEO-resembling or PPO-resembling, respectively, with a lower octanol/water partition coefficient than that of ethylene glycol and higher than that of propylene glycol.25 This hypothesis was corroborated by the correlation of macroscopic and microscopic parameters describing the solvent effect on the block copolymer self-assembly to the solvent relative polarity expressed in terms of the dielectric


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Figure 7. Progression of the microstructure in Pluronic F127-water-organic solvent ternary systems with decreasing the solvent polarity from glycols (e.g., propylene glycol) to oils (e.g., xylene). The notation is as in Figure 2. The layout of the phase diagrams in the figure is such that it leads through the evolution in the block copolymer self-assembly from polar glycols to apolar oils through solvents of intermediate polarity such as propylene carbonate, butanol, and triacetin.

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Figure 9. Plot of the polar solubility parameter, δp, versus the hydrogen bonding solubility parameter, δH, for the solvents examined here (water, propylene glycol, propylene carbonate, butanol, and xylene) as well as for glycerol, ethylene glycol, ethanol, and butyl acetate. The shaded area represents the range of polarities encompassed by the PEO-PPO-PEO block copolymer.

Figure 8. Stability composition extent of the lyotropic liquid crystalline structures in Pluronic F127-water-organic solvent systems with respect to the relative volume fraction of the organic solvent in the solvent + water mixture at two sections of the ternary phase diagrams (top) at 25 wt % Pluronic F127 and (bottom) at 53 wt % Pluronic F127. Data for propylene glycol, propylene carbonate, butanol, triacetin, and xylene are given in the same graph. The arrows represent the point of zero curvature calculated for the xylene system.

constant, octanol/water partition coefficient, or solubility parameter.25,26,36 These three parameters have given the same trends in correlations. However, this hypothesis would fail to explain the behavior of propylene carbonate if only its dielectric constant or solubility parameter were considered. Obviously the properties of this solvent are not best described by the dielectric constant or the solubility parameter. Other properties should be taken into consideration in this case. In contrast to other polar solvents studied previously such as propylene glycol, ethanol, and butanol,23,25,26 which are H-donors, propylene carbonate has an H-acceptor ability, which may be one of the reasons for its peculiar behavior. The octanol/water partition coefficient and the solubility parameter, when used as a measure of the solvent polarity, have the advantages of capturing a number of features related to the solvent polarity, including the interactions in the system and the hydrogen bonding ability. In the so-called three-dimensional solubility parameter, the overall solubility parameter is represented as a sum of individual contributions for the dispersive, polar, and hydrogen bonding interactions in the system.31 A plot of the polar solubility parameter versus the hydrogen bonding solubility parameter, rather than the overall solubility parameter, has been suggested as useful in

evaluating the solvent affinity to a given polymer.31 Such a plot for the solvents studied here and in our recent works23,26,36 is shown in Figure 9 (data for the total solubility parameter of the organic solvents are given in Table 1). The dispersive solubility parameter for all the solvents does not vary much and allows such a plot to be considered. It is obvious from Figure 9 that all the solvents examined, except for propylene carbonate, follow the expected dependence: their hydrogen bonding ability decreases as their polarity decreases. Hence, the correlations and the hypothesis proposed to rationalize the cosolvent effects on the PEO-PPO-PEO block copolymer ternary phase behavior23,26,36 worked well. At the same time, Figure 9 shows clearly that propylene carbonate deviates from this expected dependence. It has high polarity but very low H-bonding ability, which explains the low solubility in water, the tendency to phase-separate from water, and the ternary phase diagram of propylene carbonate. The low H-bonding ability, which is apparently essential in systems of PEO-PPO-PEO block copolymers, water, and organic solvent, remains masked in the case of propylene carbonate by the high-polarity contribution when the overall solubility parameter is considered. Conclusions The phase behavior and microstructure of two ternary systems consisting of an amphiphilic PEO-PPO-PEO block copolymer (Pluronic F127), water, and a pharmaceutically acceptable organic solvent (propylene carbonate or triacetin) is presented here. In the case of propylene carbonate two lyotropic liquid crystalline phases, normal micellar cubic and normal hexagonal, are identified, whereas triacetin shows a richer phase behavior with four lyotropic liquid crystalline phases, normal micellar cubic, normal hexagonal, normal bicontinuous cubic, and lamellar. For a given microstructure and at constant copolymer content the lattice spacing decreased by up to about 20% when replacing water with propylene carbonate or triacetin. By testing different locations of propylene carbonate and triacetin in the microstructure and assessing the


resulting values of the interfacial area per PEO block, it was shown that propylene carbonate and triacetin are located at the interface between the PEO-rich and the PPO-rich domains and about 20% of the organic solvent participates in the PPO-rich domains of the microstructure, similarly to butanol reported earlier.24 This conclusion on the location of propylene carbonate and triacetin is corroborated by the trends observed in the ternary phase diagrams. The phase behavior of the Pluronic F127-waterpropylene carbonate and Pluronic F127-water-triacetin systems studied here is discussed in the context of ternary systems of Pluronic F127 with polar solvents (“glycols”), for example, propylene glycol, and apolar organic solvents (“oils”), for example, xylene. Glycols can maintain the stability of one and the same microstructure up to high glycol/water ratios but do not induce development of reverse structures, and the preferred curvature of the system remains positive. Oils promote the formation of a larger variety of microstructures and have the ability to reverse the preferred curvature in the systems at sufficiently high oil/water ratios and to promote the formation of reverse structures. Solvents such as propylene carbonate, butanol, and triacetin have intermediate behavior between that of glycols and oils. They form a larger variety of microstructures than glycols and fewer microstructures but over larger stability regions than the oils. Propylene glycol (log P ) -1.41) and xylene (log P ) 3.15) are typical

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examples for a glycol and an oil respectively. The octanol/ water partition coefficient of solvents of intermediate polarity (propylene carbonate, triacetin, or butanol) is in the order of 1. The ability to control the type of the microstructures afforded by PEO-PPO-PEO block copolymers should be useful in applications. Depending on the specific requirements, a broad spectrum of microstructures, composition range of stability, and properties can be met by only selecting the solvent or varying its content. For example, stability of one and the same microstructure over large composition range or large varieties of microstructures can be easy obtained by using a glycol or an oil. The ability of pharmaceutically approved solvents to achieve the above (as shown in this study) should be of importance for pharmaceutical applications. Acknowledgment. This study was supported by the Procter and Gamble Co. University Exploratory Research Program (UERP) including a postdoctoral fellowship for R.I. The research of P.A. at Lund University is supported financially by the Swedish Natural Science Research Council (NFR). The research of P.A. in solvated block copolymers at The State University of New York is sponsored by the National Science Foundation (grant CTS-9875848). LA000373D

Evolution in Structural Polymorphism of Pluronic F127 Poly(ethylene

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