Effect of Glycols on the Self-Assembly of Amphiphilic Block

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Effect of Glycols on the Self-Assembly of Amphiphilic Block Copolymers in Water. 1. Phase Diagrams and Structure Identification 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 September 17, 1999. In Final Form: January 17, 2000 The effects of cosolvents such as glycerol, propylene glycol, ethanol, or glucose (referred here as “glycols”) on the phase behavior of a representative poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer (Pluronic P105, (EO)37(PO)58(EO)37) are presented. Regions of lamellar, bicontinuous cubic, hexagonal, and micellar cubic lyotropic liquid crystalline structures (established from small-angle X-ray scattering measurements) have been delineated in the four ternary isothermal (25 °C) PEO-PPO-PEO-water-glycol phase diagrams. Pronounced effects on the concentration range of stability of the different phases were found when the glycol was varied from ethanol (the least polar glycol examined here) to glucose (the most polar). For example, glycerol and glucose swell the hexagonal phase to lower copolymer content, while propylene glycol and ethanol do not show this effect. Our experimental observations are discussed in terms of modification of the system “interfacial curvature” affected through the ability of different glycols to swell the PEO-PPO-PEO macromolecule to different extents. A hypothesis is proposed, based on a correlation between the PEO-PPO-PEO-water-glycol phase behavior and the glycol polarity, to account for and predict the effect of glycols on the ternary phase behavior of PEOPPO-PEO block copolymers.

* To whom correspondence should be addressed at the State University of New York. E-mail: [email protected]. † Lund University. ‡ On leave from the Institute of Physical Chemistry, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria. § The State University of New York at Buffalo.

and reverse liquid crystalline microstructures, as demonstrated in recent reports.5,7-11 For a given block copolymer-water binary system, the type and the number of the microstructures formed depend on the initial interfacial curvature, which is set by the copolymer macromolecular architecture (e.g., its molecular weight and PEO/PPO ratio). In general, the different microstructures appear along the copolymer-water axis with increasing the copolymer concentration in the sequence: spherical micelles (micellar solution and micellar cubic liquid crystalline phase), cylindrical micelles (hexagonal liquid crystalline phase), planar micelles (lamellar liquid crystalline phase), which implies a decrease of the preferred curvature. As we have shown,5 the initial interfacial curvature can be readily modified by the ability of the copolymer blocks to swell to different extents with selective solvents. Thus the proper solvent selection offers a large diversity in the microstructure and the corresponding properties. Modification of the phase behavior of the PEO-PPO-PEO block copolymers in water by using oils of different polarity (xylene, butyl acetate, or butanol) has been recently reported.9,12 Due to the great potential for modification of their phase behavior and to the variety of their physicochemical properties, Poloxamers find numerous industrial applications.13 For many applications, however, it is important to gain knowledge for the Poloxamer phase

(1) Alexandridis, P. Curr. Opin. Colloid Interface Sci. 1997, 2, 478489. (2) Pluronic and Tetronic Block Copolymer Surfactants; Technical Brochure, BASF Corp., 1989. (3) Alexandridis, P.; Hatton, T. A. In Polymeric Materials Encyclopedia; Salamone, J. C., Ed.; CRC Press: Boca Raton, FL, 1996; pp 743754. (4) Olsson, U.; Wennerstro¨m, H. Adv. Colloid Interface Sci. 1994, 49, 113. (5) Alexandridis, P.; Olsson, U.; Lindman B. Langmuir 1998, 14, 2627-2638. (6) Evans, D. F.; Wennerstro¨m, H. The Colloidal Domain, 2nd ed.; Wiley-VCH: New York, 1999.

(7) Alexandridis, P.; Olsson, U.; Lindman, B. Macromolecules 1995, 28, 7700-7710. (8) Alexandridis, P.; Zhou, D.; Khan, A. Langmuir 1996, 12, 26902700. (9) Holmqvist, P.; Alexandridis, P.; Lindman, B. Macromolecules 1997, 30, 6788-6797. (10) Svensson, B.; Alexandridis, P.; Olsson, U. J. Phys. Chem. B 1998, 102, 7541-7548. (11) Svensson, M.; Alexandridis, P.; Linse, P. Macromolecules 1999, 32, 5435-5443. (12) Holmqvist, P.; Alexandridis, P.; Lindman, B. J. Phys. Chem. B 1998, 102, 1149-1158.

Introduction Amphiphilic triblock copolymers consisting of a relatively hydrophobic poly(propylene oxide) (PPO) middle block and two hydrophilic poly(ethylene oxide) (PEO) end blocks are commercially available as Poloxamers or Pluronics in a large variety of molecular weights and PEO/ PPO ratios.1,2 In the presence of a solvent selective for the hydrophilic PEO blocks, such as water, and a solvent selective for the hydrophobic PPO block, such as xylene (“oil”), PEO-PPO-PEO block copolymers self-organize into a variety of lyotropic liquid crystalline “gel” phases with lamellar, hexagonal, or (micellar or bicontinuous) cubic structure (respectively, with one-, two-, and threedimensional order).3 Both oil-in-water (“normal”) and water-in-oil (“reverse”) morphologies can be formed.4,5 A notable feature that distinguishes the self-assembling behavior of the PEO-PPO-PEO block copolymers from that of the low-molecular-weight surfactants6 is the ability of the block copolymers to exhibit much richer structural polymorphism and to form a great variety of both normal

10.1021/la991235v CCC: $19.00 © 2000 American Chemical Society Published on Web 03/03/2000

Self-Assembly of Block Copolymers

behavior in the presence of nonaqueous polar solvents or mixed solvents. A recent study of the phase behavior and microstructure of a representative PEO-PPO-PEO block copolymer in a binary system with formamide14 has shown that (i) the stability ranges of the liquid crystalline phases formed in formamide are shifted to higher copolymer concentrations compared to water and (ii) the interfacial area per PEO block in the lamellar and hexagonal structures is higher in formamide than in water. The influence of cosolutes (e.g., inorganic salts and urea) as well as cosolvents (such as ethylene glycol, ethanolamine, alcohols, and formamide) on the micellization process in dilute aqueous solutions has been studied for some PEOPPO-PEO block copolymers.15-22 The observed changes (increase or decrease) of the critical micellization concentration or cloud point upon the addition of cosolvents or cosolutes have been attributed to changes in the water solvent quality. A few studies22,23 on the gelation process in PEO-PPO-PEO block copolymer systems report strong dependence of the temperature (the copolymer concentration) of the solution/gel transition on the presence of cosolutes (inorganic salts or homopolymers) which influence the micellization process. The few available investigations24-29 of the micellization process and the formation of liquid crystalline phases of low-molecular weight surfactants and lipids in nonaqueous polar solvents, such as alcohols and formamide, show that micelles start to form at considerably higher surfactant concentration and are considerably smaller than those formed in water.24,25 The stability regions of the liquid crystalline phases are narrower, and fewer microstructures are formed in the presence of such solvents compared to water.24,26 Studies on the effect of polyols (e.g., glycerol, propylene glycol, 1,3-butanediol) on the phase behavior and microstructure of alkyl-oligo(ethylene oxide) ether surfactants using small-angle X-ray scattering have been recently reported.30,31 The observed increase (decrease) of the lattice spacing in the hexagonal liquid crystalline phase induced by some additives has been explained by dehydration (hydration) of the poly(ethylene oxide) chain of the surfactants and corresponding decrease (increase) of the surfactant hydrophilicity upon the addition of polyols. (13) Alexandridis, P. Curr. Opin. Colloid Interface Sci. 1996, 1, 490501. (14) Alexandridis, P. Macromolecules 1998, 31, 6935-6942. (15) Alexandridis, P.; Spontak, R. J. Curr. Opin. Colloid Interface Sci. 1999, 4, 130-139. (16) Alexandridis, P.; Andersson, K. J. Colloid Interface Sci. 1997, 194, 166-173. (17) Alexandridis, P.; Holzwarth, J. F. Langmuir 1997, 13, 60746082. (18) Armstrong, J.; Chowdhry, B.; Mitchell, J.; Beezer, A.; Leharne, S. J. Phys. Chem. 1996, 100, 1738-1745. (19) Alexandridis, P.; Athanassiou, V.; Hatton, T. A. Langmuir 1995, 11, 2442-2450. (20) Cheng, Y.; Jolicoeur, C. Macromolecules 1995, 28, 2665-2672. (21) Bahadur, P.; Pandya, K.; Almgren, M.; Li, P.; Stilbs, P. Colloid Polym. Sci. 1993, 271, 657-667. (22) Jo¨rgensen, E.; Hvidt, S.; Brown, W.; Schille´n, K. Macromolecules 1997, 30, 2355-2364. (23) Malmsten, M.; Lindman, B. Macromolecules 1993, 26, 12821286. (24) Sjo¨berg, M.; Wa¨rnheim, T. Surf. Sci. Ser. 1997, 67, 179-205. (25) Penfold, J.; Staples, E.; Tucker, I.; Cummins, P. J. Colloid Interface Sci. 1997, 185, 424-431. (26) Martino, A.; Kaler, E. Colloids Surf., A 1995, 99, 91-99. (27) Jonstro¨mer, M.; Strey, R. J. Phys. Chem. 1992, 96, 5993-6000. (28) Friberg, S. E.; Liang, Y. C.; Lockwood F. E. J. Dispersion Sci. Technol. 1987, 8, 407-422. (29) Alfons, K.; Engstro¨m, S. J. Pharm. Sci. 1998, 87, 1527-1530. (30) Iwanaga, T.; Suzuki, M.; Kunieda, H. Langmuir 1998, 14, 57755781. (31) Aramaki, K.; Olsson, U.; Yamaguchi, Y.; Kunieda, H. Langmuir 1999, 15, 6226-6232.

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The present study extends our previous investigation9 on the role of the oil type on the phase behavior of PEOPPO-PEO block copolymers to address the role of various polar cosolvents (glycerol, propylene glycol, ethanol, and glucose, referred to for simplicity as “glycols”). The objective is to study the effects of glycols on the PEOPPO-PEO block copolymer phase behavior and microstructure and to quantify these effects in terms of the glycol physicochemical parameters. The ultimate goal is to be able to predict the effects of cosolvents. In the first part of this investigation, results on the general isothermal ternary phase behavior are presented (“macroscopic” information), while the second part32 is concerned with an in-depth analysis of the role of glycols on the microstructure (“microscopic” information). This study has fundamental significance toward an improved understanding of the modulation of block copolymer microstructure as well as practical significance, e.g., in pharmaceutical formulations. The results presented here are organized as follows. First, the microstructure of the liquid crystalline phases obtained in each ternary system is characterized by analyzing the corresponding small-angle X-ray scattering diffraction patterns. Then, the overall phase behavior in the ternary systems of the four different glycols is examined. The discussion of the results focuses on the glycol effects on the phase behavior and the modification of the interfacial curvature through the ability of the different glycols to swell different blocks of the macromolecule to different extents. A correlation between the effects of the glycols on the phase behavior and their relative polarity is made. Materials and Methods Materials. The poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer, Pluronic P105, was obtained as a gift from BASF Corp. and used as received. According to the manufacturer2 it has molecular weight of 6500 and 50 wt % content of poly(ethylene oxide). On the basis of these data, Pluronic P105 can be represented as (EO)37(PO)58(EO)37. Glycerol (p.a.) was purchased from Prolabo, Fontenay, France. Propylene glycol (1,2-propanediol) (p.a.) and D(+)-glucose monohydrate (g99%) were purchased from Fluka Chemie AG, Buchs, Switzerland. Ethanol (spectrographic grade, g99.5%) was purchased from Kemetyl AB, Haninge, Sweden. The structural formulas of Pluronic P105 as well as of the glycols studied here are shown in Figure 1. Some basic physicochemical properties of the glycols are given in Table 1.33,34 Judging from their dielectric constants and dipole moments, glycerol, propylene glycol, ethanol, and glucose are all hydrophilic. The notation “glycols”, used to refer to all three polar cosolvents (glycerol, propylene glycol, and ethanol) and glucose, emphasizes their polarity and chemical classification as polyols. It is introduced here in order to simplify the presentation of the results. Determination of the Phase Diagrams. For each copolymer-water-glycol system, a large number of samples of various compositions covering the whole range of the ternary phase diagram were prepared by weighing the appropriate amounts of copolymer, Millipore-treated water, and glycol into 8 mm (i.d.) glass tubes and flamesealed immediately after. The samples were centrifuged several times over several days in alternating directions (32) Alexandridis, P.; Ivanova, R.; Lindman B. Langmuir 2000, 16, 3676. (33) Handbook of Chemistry and Physics; Lide, D., Ed.; CRC Press: Cleveland, OH, 1994. (34) McClellan, A. L. Tables of Experimental Dipole Moments; Rahara Enterprises: El Cerrito 1974.

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Figure 1. Chemical structure of Pluronic P105 and the glycols used in this study. Table 1. Physicochemical Parameters of the Glycols Examined Here solvent

MWa

mpb

bpc

water 18.01 0 100 glycerol 92.10 18 290 glucose 180.16 150 propylene 76.10 -60 188 glycol ethanol 46.07 -114 78

densityd dielectric dipole (g/cm3) constantd momente 0.9982 1.2567 1.5620 1.0327

78.5 40.1

0.7873

24.3

3.11 2.68 14.1

32.0 1.69

a

Molecular weight. b Melting point, °C. c Boiling point, °C. d The density and the dielectric constant of solvents are given at 25 °C. The data are taken from ref 33. e The dipole moment data (in debye units) are taken from ref 34.

in order to facilitate mixing and allowed to reach equilibrium at 25 ( 0.5 °C. The samples were monitored over a period of several months for birefringence and changes in their appearance by inspection under polarized light. The thermodynamic equilibrium state was considered reached when no changes with time were observed in all samples. No changes in the structure over such a time scale are a good indication of thermodynamic stability since there are no diffusion limitations in the systems studied and the slowest diffusional movement would be completed in about a month. The ability to reproduce the structure of samples of a given composition at different time periods is another indication for this. The one-phase samples are macroscopically homogeneous, clear, and transparent, whereas the multiple-phase samples are either homogeneous and not clear or macroscopically heterogeneous and phase-separated. The samples in the micellar solution, micellar and bicontinuous cubic liquid crystalline phases, are optically isotropic (nonbirefringent), while those in the hexagonal and lamellar liquid crystalline phases are anisotropic (birefringent). The ternary isothermal phase diagram for each system studied was drawn distinguishing in the above way between onephase regions with different microstructures and multiplephase regions. The phase boundaries were verified, and small corrections were made where necessary, based on small-angle X-ray scattering patterns (a few samples which appeared macroscopically homogeneous resulted in patterns consisting of a superposition of reflections from two different microstructures).

Small-Angle X-ray Scattering (SAXS). SAXS measurements were performed on a Kratky compact smallangle system equipped with a position-sensitive detector (OED 50M, Mbraun, Graz, Austria) consisting of 1024 channels of 53.0 µm width each. Cu KR radiation of wavelength 1.542 Å was provided by a Seifert ID-300 X-ray generator, operating at a maximum intensity of 50 kV and 40 mA. A 10 µm thick Ni filter was used to remove the Kβ radiation, and a 1.5 mm W filter was used to protect the detector from the primary beam. The sample-todetector distance was 277 mm. The camera volume was kept under vacuum during the measurements in order to minimize the background scattering from air. The temperature was controlled and kept at 25 ( 0.1 °C by using a Peltier element. The sample holder was an 1 mm quartz capillary which was filled with the samples by using a syringe. The viscosity of the samples in the hexagonal and micellar cubic liquid crystalline phases was higher than that in the lamellar liquid crystalline phase, but it was still possible to fill in the capillary. However, the samples in the bicontinuous cubic liquid crystalline phase were rather stiff. In these cases a sample holder for pastelike and solid materials was used. Characterization of the Microstructure. The microstructure and the characteristic length scales of the liquid crystalline phases were established through analysis of the SAXS diffraction patterns. The obtained Bragg diffraction peaks are relatively sharp and allow us to evaluate the peak positions directly from the slit-smeared spectra.7,8 Despite this and the small difference (within a few angstoms) between slit-smeared and desmeared data, we have evaluated the peak positions from the desmeared spectra deeming this way methodologically more precise. The desmearing was done according to the direct method of beam-height correction.35 The microstructure of the liquid crystalline phases was determined from the relative positions of the Bragg diffraction peaks. For the lamellar and hexagonal structures the relative positions of the peaks should obey, respectively, the relationship 1:2:3:4... and 1:x3:2:x7:3... Two parameters are characteristic of the microstructure: the lattice parameter (the repeat distance, d, in the lamellar structure and the distance between the centers of adjacent cylinders, a, in the hexagonal structure, see Figure 2) and the interfacial area per PEO block, ap (the area that a PEO block of the PEO-PPO-PEO block copolymer occupies at the interface between polar and apolar domains). When the lattice parameters in the lamellar and the hexagonal structures are compared, instead of a in the hexagonal structure we prefer to use the distance between the planes of the centers of two adjacent rows of cylinders, d, which is related to a through a simple geometrical relation (see Figure 2). Further as lattice parameter in the hexagonal structure we will discuss only the distance d. Here, the lattice parameter and especially the interfacial area, will be used in the establishment of the crystallographic space group of the cubic liquid crystalline structures. In the hexagonal and lamellar structures, the lattice parameter is given directly by the position, q*, of the first and the most intense diffraction peak:

d ) 2π/q*

(1)

The determination of the interfacial area per PEO block, however, is more complicated and involves some assump(35) Singh, M.; Ghosh, S.; Shannon, R. J. Appl. Crystallogr. 1993, 26, 787.


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Figure 2. Schematic of the different microstructures of the lyotropic liquid crystalline phases attained from the block copolymer self-assembly in the presence of selective solvents. The polar domains are given shaded, while the apolar are blank. The Gyroid minimal surface is used as a representation of the bicontinuous cubic structures. The notation used to indicate the different microstructures is the same as that used in Figure 3. The lattice parameter (d in the lamellar structure and a in the hexagonal) as well as the distance between the planes of the centers of two adjacent rows of cylinders, d, in the hexagonal structure are denoted.

tions. For detailed analysis and discussion of the calculation of the interfacial area in the lamellar and hexagonal structures, the assumptions made, and the trends in the glycol effects on the microstructure, see the companion paper.32 The establishment of the crystallographic space group of the cubic liquid crystalline phases (of both micellar or bicontinuous structure) is more complex than that of the lamellar and hexagonal structures and not always definite. The proper indexing of the cubic structure to a crystallographic space group is often ambiguous due to the small number of reflections and their relatively lower intensities. It is usually necessary to consider not only the relative positions of the diffraction peaks but also their relative intensities as well as other criteria, like the number of missing peaks, the values of the lattice parameter, and the interfacial area per PEO block. The indexing of the SAXS diffraction peaks to a crystallographic group was assessed by plotting the reciprocal spacing, 1/dhkl, of the reflections versus the sum of the Miller indices, (h2 + k2 + l2)1/2. For a correct assignment this plot is linear and passes through the origin. The lattice parameter, R, is given by the slope of this plot. In the normal micellar cubic structure the interfacial area per PEO block can be calculated from:7,36

ap ) (36πnu f2)1/3

υp 2ΦpR

(2)

where 0.54 is the volume fraction of the PPO block in the P105 macromolecule (the PPO weight fraction is 0.50, which makes up ∼0.54 volume fraction). The volume of one macromolecule is υp ≈ 10 300 Å3 for P105. To convert the weight fractions of the components into volume fractions, the bulk densities of the copolymer (1.05 g/cm3) and water and glycols (given in Table 1) are used. The aggregation number of the micelles, Nagg, can be determined using5

Nagg ) ΦpR3/nuυp

(4)

The bicontinuous cubic structure can be represented by a multiply connected bilayer, the midplane of which can be modeled as a minimal surface, and the polar/apolar interface can be described as two parallel surfaces displayed on the opposite sides of the minimal surface, each at a distance L.37 In the normal bicontinuous cubic structure the interfacial area per PEO block can be calculated from the relations:37,38

ap )

(

( ))

συp 2πχu L 1+ ΦpR σ R

2

(5)

and

1-f)

(

( ))

2πχu L 2σL 1+ R 3σ R

2

(6)

(3)

where σ is the dimensionless area per unit cell, χu is the Euler characteristic per unit cell, and 1 - f is the polar volume fraction (the volume fraction enclosed between the two parallel polar/apolar interfaces surrounding the minimal surface). For a given minimal surface, σ and χu are known quantities, thus allowing eq 6 to be solved for L, and then the interfacial area can be calculated from eq 5. In the cubic liquid crystalline phases, both lattice parameter and interfacial area depend on the crystallographic space group. The calculation of the interfacial area involves the number of the micelles that constitute

(36) Alexandridis, P.; Olsson, U.; Lindman, B. Langmuir 1997, 13, 23-34.

(37) Hyde, S. J. Phys. Chem. 1989, 93, 1458-1464. (38) Anderson, D.; Wennerstro¨m, H.; Olsson, U. J. Phys. Chem. 1989, 93, 4243-4253.

where nu is the number of the spherical micelles (structural elements) in the cubic cell, f is the apolar volume fraction, υp is the volume of one P105 macromolecule, Φp is the copolymer volume fraction in the ternary system, and R is the lattice parameter. The apolar volume fraction is given by eq 3 according to the following assumptions: (i) the copolymer is the only surface active component in all ternary systems, and (ii) the polar domains consist of the PEO blocks, water, and glycol, while the apolar domains consist only of the PPO blocks of the copolymer.

f ) 0.54Φp

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Figure 3. Effect of glycols on the phase behavior of Pluronic 105 in water at 25 °C: (top left) P105-water-glycerol system, (top right) P105-water-propylene glycol system, (bottom left) P105-water-glucose system, (bottom right) P105-water-ethanol system. L1 denotes the ternary composition region of liquid clear isotropic solution. I1 denotes the region where the samples are clear isotropic gels and the microstructure is that of spherical micelles arranged in a cubic lattice. H1 denotes the region where the samples are clear birefringent gels and the microstructure is that of cylindrical micelles arranged in a hexagonal lattice. V1 denotes the region where the samples are clear isotropic (hard) gels and the microstructure is that of interconnected (bicontinuous) cylindrical micelles arranged in a cubic lattice. LR denotes the region where the samples are clear birefringent (soft) gels and the microstructure is that of lamellae-planar micelles. The composition is given in weight fractions. The boundaries of the one-phase regions are drawn with solid lines.

one unit cell (in the micellar cubic structure) or parameters characterizing the minimal surface (in the bicontinuous structure) which are specific for a given crystallographic space group. An agreement between the ap calculated in the different microstructures of the phase diagram has proved to be strong support to the correct assignment of the cubic lattice to a crystallographic space group.10,14 Results and Analysis A. Structural Characterization of the Lyotropic Liquid Crystalline Phases. Several one-phase regions were observed in each of the ternary isothermal (25 °C) phase diagrams studied of Pluronic P105 in the presence of water and each of the four glycols shown in Figure 3 (the phase boundaries are drawn with solid lines in the figure). The microstructure of the delineated lyotropic liquid crystalline “gel” phases, normal micellar cubic (I1),

normal hexagonal (H1), lamellar (LR), and normal bicontinuous cubic (V1), was established through analysis of the corresponding SAXS diffraction patterns measured in each phase. Lamellar Lyotropic Liquid Crystalline Phase (Lr). The samples in the lamellar liquid crystalline region have the simplest, one-dimensional, microstructure consisting of lamellae (planar micelles). A schematic of the structure is given in Figure 2. Macroscopically the samples in the LR region are clear birefringent (soft) gels. The SAXS diffraction patterns obtained for the samples at 75 wt % P105 are shown in Figure 4. The relative positions of the Bragg peaks of the diffraction patterns follow the expected sequence for a lamellar structure: 1:2:3... In each system two to three peaks following this sequence are usually registered, confirming the lamellar microstructure. The lattice parameter, d, was obtained directly from the


Langmuir, Vol. 16, No. 8, 2000 3665

Figure 4. SAXS diffraction patterns obtained from lamellar, LR, samples at 75 wt % copolymer concentration and at various glycol contents. The layout of the graphs is the same as that used for the ternary phase diagrams: (top left) P105-water-glycerol system, (top right) P105-water-propylene glycol system, (bottom left) P105-water-glucose system, (bottom right) P105-water-ethanol system. The glycol content for each diffraction pattern is given above the corresponding curve. The diffraction patterns have been shifted by multiplying them by an appropriate number to avoid overlapping. The relative diffraction peak intensities are comparable since all spectra were recorded under the same conditions.

position of the first peak of the SAXS spectra using eq 1. The results for the lattice parameter together with the interfacial area per PEO block are summarized in Table 2. The data for these two parameters, calculated in the lamellar and the hexagonal structure, will be used latter in the structural characterization of the cubic liquid crystalline phases, micellar and bicontinuous. For details in the calculation of the interfacial area and a discussion of the trends in the effects shown by the different glycols on the lattice parameter and the interfacial area, see the companion paper.32 A comparison of the SAXS diffraction patterns (Figure 4) reveals some common trends when water is replaced by a glycol: (i) the intensity of the first diffraction peak increases relative to that of the higher order reflections, and (ii) higher order peaks tend to vanish (without a

distinguishable increase in the main peak intensity). The increase of the main peak intensity is more pronounced in the cases of glycerol and glucose, while the vanishing of the higher order peaks is more pronounced in the case of ethanol. These tendencies are most probably connected to the electron density of the compounds (changing the contrast between the solvent and the copolymer) as well as to possible rearrangements in the microstructure (change the degree of intermixing upon replacing water with glycol). Normal Hexagonal Lyotropic Liquid Crystalline Phase (H1). The hexagonal liquid crystalline microstructure has two-dimensional order and consists of cylindrical micelles packed in a hexagonal lattice (Figure 2). The samples in the H1 region are clear birefringent gels, usually stiffer than the lamellar ones. The SAXS diffraction

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Table 2. Characteristic Parameters in the Lr and H1 Liquid Crystalline Phases phase and glycol LR glycerol glucose propylene glycol ethanol H1 glycerol glucose propylene glycol ethanol

Φp

volume fractions Φwater

Φglycol

apolar vol fraction f

lattice parameter d (Å)

interfacial area ap (Å2)

0.74 0.75 0.76 0.74 0.77 0.74 0.73 0.75 0.73 0.72

0.26 0.21 0.16 0.22 0.16 0.21 0.17 0.10 0.20 0.15

0 0.04 0.08 0.04 0.07 0.05 0.10 0.15 0.07 0.13

0.40 0.40 0.41 0.40 0.42 0.40 0.39 0.40 0.39 0.39

111.5 112.3 111.5 113.9 112.3 104.2 103.5 93.8 102.2 94.9

125 123 122 123 119 133 136 148 138 151

0.49 0.49 0.50 0.50 0.50 0.51 0.52 0.49 0.49 0.49 0.48 0.47 0.47

0.51 0.47 0.42 0.37 0.47 0.42 0.38 0.46 0.41 0.36 0.46 0.40 0.34

0 0.04 0.08 0.13 0.03 0.07 0.10 0.05 0.10 0.15 0.06 0.13 0.19

0.26 0.27 0.27 0.27 0.27 0.27 0.28 0.26 0.26 0.26 0.26 0.25 0.25

118.1 119.9 120.8 122.6 120.0 122.2 124.5 117.2 115.5 112.3 110.7 103.5 97.8

151 148 146 143 148 144 139 152 154 159 163 175 186

patterns obtained for samples at 50 wt % P105 are shown in Figure 5. The relative positions of the Bragg diffraction peaks follow the sequence expected for a hexagonal structure: 1:x3:2:x7... In each SAXS diffraction pattern three to five peaks following this sequence are usually registered confirming the hexagonal microstructure. As in the lamellar microstructure, more (and/or more intense) peaks are observed in the case of glycerol and glucose. On the contrary, ethanol, and to a lesser extent propylene glycol, has a tendency to decrease the intensities of the higher order peaks, without showing distinguishable tendency of developing peaks. The lattice parameter, d, in the hexagonal phase (as in the lamellar one) was obtained directly from the position of the first peak of the SAXS spectra (eq 1). The results for the lattice parameter and the interfacial area are given in Table 2. Normal Bicontinuous Cubic Lyotropic Liquid Crystalline Phase (V1). The V1 microstructure is obtained in a limited composition region at 25 °C only in the systems P105-water-propylene glycol and P105-waterethanol (Figure 3). The bicontinuous cubic phases are of special interest because of their intricate microstructure (shown schematically in Figure 2) and potential applications in drug delivery systems and pharmaceutical formulations, e.g.29 Two representations, which can converge topologically, are common to describe the V1 microstructure: interconnected (bicontinuous) cylindrical micelles or interconnected bilayers arranged in a cubic lattice. Macroscopically the V1 samples are clear, optically isotropic, and very stiff gels. SAXS diffraction patterns of three samples were recorded in each V1 region (shown in Figure 6). The most commonly observed crystallographic space group for the bicontinuous cubic phases of surfactants and lipids,39,40 as well as in amphiphilic PEO-PPO-PEO block copolymer systems,5,7 is Ia3d. It features two characteristic Bragg peaks: the first and most intense at Miller indices hkl ) 211, and a “shoulder” at hkl ) 220. The first two Bragg peaks in each diffraction pattern shown in Figure 6 were indexed as 211 and 220. Two to four higher order (39) Fontell, K. Colloid Polym. Sci. 1990, 268, 264-285. (40) Mariani, P.; Luzzati, V.; Delacroix, H. J. Mol. Biol. 1988, 204, 165-189.

diffraction peaks in each spectra, though of 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 shown in Figure 7. Therefore, the cubic lattice is assigned to the Ia3d crystallographic space group. The cubic lattice of the Ia3d space group is consistent with that afforded by the Gyroid minimal surface.39,40 The microstructure of the Ia3d space group can be visualized as interconnected polar bilayers (channels), consisting in this case of the PEO blocks of the copolymer and water, separating two apolar domains, consisting of the PPO block of the copolymer and (possibly) propylene glycol or ethanol. The lattice parameter is given by the slope of the plot shown in Figure 7. The interfacial area per PEO block and the thickness of the polar bilayer were calculated through eqs 5 and 6. For the Gyroid minimal surface χu ) -8 and σ ) 3.091.41 The results are given in Table 3. The comparison of the calculated values of the interfacial area with those obtained for propylene glycol and ethanol in the adjacent lamellar and hexagonal phases (compare column 7 in Table 2 and Table 3) shows that they are in a very good agreement and follow the expected trends (see ref 32). Such agreement supports the assignment of the bicontinuous cubic structure to the Ia3d crystallographic space group, consistent with a Gyroid minimal surface. Normal Micellar Cubic Lyotropic Liquid Crystalline Phase (I1). Macroscopically the samples in the I1 region are clear optically isotropic (nonbirefringent) gels. The microstructure of the micellar cubic phase can be visualized as discrete micelles (spherical, slightly elongated, or disklike) which have crystallized in a cubic lattice (shown schematically in Figure 2). The structural elements (micelles) can be arranged in a large number of cubic lattices belonging to different crystallographic space groups.39,40 The positions of the Bragg diffraction peaks obey different relationships for the different space groups. However, all space groups can be classified in three main families of cubic lattices:40 primitive (P...), body-centered (I...), and face-centered (F...). The SAXS diffraction pat(41) Anderson, D.; Davis, H.; Scriven, L.; Nitsche, J. Adv. Chem. Phys. 1990, 77, 337.


Langmuir, Vol. 16, No. 8, 2000 3667

Figure 5. SAXS diffraction patterns obtained from hexagonal samples, H1, at 50 wt % copolymer concentration and at various glycol contents. The layout of the graphs is the same as used for the ternary phase diagrams: (top left) P105-water-glycerol system, (top right) P105-water-propylene glycol system, (bottom left) P105-water-glucose system, (bottom right) P105-waterethanol system. The glycol content for each diffraction pattern is given above the corresponding curve. The diffraction patterns have been shifted by multiplying them by an appropriate number to avoid overlapping. The relative diffraction peak intensities are comparable since all spectra were recorded under the same conditions.

terns obtained for the samples in the I1 phase are shown in Figure 8. Four to eight Bragg peaks can be identified in each diffraction pattern, with the higher order peaks having very low intensities. As it is seen from Figure 8, the SAXS diffraction patterns are very similar in the cases of glycerol, propylene glycol, and glucose. However, the one obtained for the P105-water-ethanol system differs (see the discussion below). Although it is arduous to check all possible cubic structures against the experimental SAXS spectra, we can exclude certain crystallographic space groups on the basis of the relative positions of the observed reflections. Thus the face-centered cubic lattice can be ruled out for all of the experimental diffraction patterns, because none of them follows its reflection relationship. Distinguishing between I... and P... cubic lattices is more difficult because the reflections afforded

by the P... structure include as a subset those afforded by the I... structure. To check the experimental data against the sequence expected for the I... and P... structures, the reciprocal dhkl spacings of the peaks in each diffraction pattern were plotted versus the function of the Miller indices (h2 + k2 + l2)1/2. Two typical 1/dhkl versus (h2 + k2 + l2)1/2 plots are shown in Figure 9. As is evident, both assignments are equally possible. In this case we need to involve more criteria in resolving the cubic structure. In simple primitive or body-centered cubic lattices, the first peak is the most intense one, while in more complex structures this rule does not hold. Indeed, in the experimental SAXS diffraction patterns for glycerol, propylene glycol, and glucose the first diffraction peak is the most intense. Therefore, in this cases we are dealing with simple

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Figure 6. SAXS diffraction patterns obtained from bicontinuous cubic, V1, samples: (top) P105-water-propylene glycol system, and (bottom) P105-water-ethanol system. The composition of the samples for each diffraction pattern is given above the corresponding curve. The diffraction patterns have been shifted by multiplying them by an appropriate number to avoid overlapping. The relative diffraction peak intensities are comparable since all spectra were recorded under the same conditions. The identified diffraction peaks used in the assignment of the cubic lattice are indicated with arrows.

primitive or body-centered structures. The case of ethanol is a more complex structure. We will first consider the cases of glycerol, propylene glycol, and glucose. In the assignment to the body-centered structure, the Bragg diffraction peak with Miller indices hkl ) 200 is systematically missing in all experimental spectra except for those at the highest glycerol and propylene glycol concentrations where an indication for its presence is evident. In the assignment to the primitive structure, the Bragg peak with hkl ) 110 is missing. Dealing with simple structures, however, allows us to compare both the lattice parameter, R, and the interfacial area per PEO block, ap, with the corresponding values obtained for the neighboring hex-

Ivanova et al.

Figure 7. Two representative plots of the reciprocal d spacings (1/dhkl) of the identified reflections versus the sum of the Miller indices (h2 + k2 + l2)1/2 for the SAXS spectra of V1 samples (the sample composition is indicated in the figure). The Miller indices to which the diffraction peaks are indexed are denoted in the graphs.

agonal and lamellar structures. The lattice parameter is obtained from the slope of the 1/dhkl versus (h2 + k2 + l2)1/2 plot. These data were used to calculate the interfacial area per PEO block and the aggregation number using eqs 2 and 4. In these equations nu ) 1 for the unit cell of the primitive cubic lattice consisting of one micelle and nu ) 2 for that of the body-centered lattice consisting of two micelles. The results for both primitive and bodycentered lattices are given in Table 4. The comparison of the values of the lattice parameter and the interfacial area with those obtained in the hexagonal and lamellar phases (compare column 7 in Table 2 and Table 4) shows that, although we expect (for decreasing Φp) an increase in R and ap, the lattice parameter for the body-centered structure is considerably higher and the interfacial area per PEO block is considerably lower than expected (see ref 32). Therefore, we consider the primitive structure as more plausible.


Langmuir, Vol. 16, No. 8, 2000 3669

Table 3. Characteristic Parameters in the V1 Liquid Crystalline Phase (Structure Consistent with Ia3d Crystallographic Space Group, Gyroid Minimal Surface)

glycol

Φp

propylene glycol

0.69 0.69 0.64 0.65 0.62 0.56

ethanol

volume fractions Φwater Φglycol 0.16 0.11 0.10 0.27 0.25 0.25

0.15 0.20 0.25 0.08 0.13 0.19


lattice parameter R (Å)


polar film thickness 2L (Å)

0.37 0.37 0.35 0.35 0.34 0.30

262 259 246 267 260 244

142 144 159 146 154 175

56 56 56 60 60 60

Figure 8. SAXS diffraction patterns obtained from micellar cubic, I1, samples at 30 wt % copolymer concentration and at various glycol contents. The layout of the graphs is the same as that used for the ternary phase diagrams: (top left) P105-water-glycerol system, (top right) P105-water-propylene glycol system, (bottom left) P105-water-glucose system, (bottom right) P105-waterethanol system. The glycol content for each diffraction pattern is given above the corresponding curve. The diffraction patterns have been shifted by multiplying them by an appropriate number to avoid overlapping. The relative diffraction peak intensities are comparable since all spectra were recorded under the same conditions. The identified diffraction peaks used in the assignment of the cubic lattice are indicated with arrows.

However, for the P105-water-ethanol system the R and ap values for either primitive or body-centered lattice do not fit to the trends followed by the other three systems (for details see the companion paper32). This is evidence

that assignment to a simple I... or P... cubic lattice is not correct. We consider the crystallographic space group Pm3n as more likely in the case of ethanol (in the concentration range examined here). The Pm3n space

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Ivanova et al.

Figure 9. Two representative plots of the reciprocal d spacings (1/dhkl) of the identified reflections versus the sum of the Miller indices (h2 + k2 + l2)1/2 for the SAXS spectra of I1 samples (the sample composition is indicated in the figure). The Miller indices to which the diffraction peaks are indexed are denoted in the graphs. The two possible indexations are given. Table 4. Characteristic Parameters in the I1 Liquid Crystalline Phase

lattice and glycol primitive glycerol glucose propylene glycol ethanol body centered glycerol glucose propylene glycol ethanol Pm3n, ethanol

Φp

volume fractions Φwater Φglycol


lattice parameter R (Å)


aggregation no., Nagg

0.29 0.29 0.30 0.29 0.31 0.29 0.29 0.28

0.71 0.61 0.53 0.63 0.55 0.61 0.50 0.59

0 0.10 0.17 0.08 0.14 0.10 0.21 0.13

0.16 0.16 0.16 0.16 0.17 0.16 0.16 0.15

140 148 153 150 161 138 134 148

178 169 161 166 151 181 186 170

77 90 105 96 127 74 68 92

0.29 0.29 0.30 0.29 0.31 0.29 0.29 0.28

0.71 0.61 0.53 0.63 0.55 0.61 0.50 0.59

0 0.10 0.17 0.08 0.14 0.10 0.21 0.13

0.16 0.16 0.16 0.16 0.17 0.16 0.16 0.15

196 203 212 212 222 194 186 206

160 155 146 148 138 162 169 154

106 117 140 135 166 103 91 120

0.28

0.59

0.13

0.15

206

244

29

group is common in systems of surfactants and lipids.39,40 It has been observed in some PEO-PPO-PEO block copolymer systems10,14 as well. The cubic lattice of the crystallographic space group Pm3n consists of eight short rodlike (with axial ratio of 1.2-1.3) micelles per unit cell, two of them having complete rotational freedom and the other six only lateral rotational freedom.39 A value of 244 Å2 was obtained for the interfacial area (in eqs 2 and 4, nu ) 8). While it is significantly larger than that obtained for the neighboring H1 (Table 2), the interfacial area for the Pm3n space group in the case of ethanol follows the trends observed in the other liquid crystalline phases (see ref 32). As we have already pointed out, the SAXS diffraction patterns of cubic phases are in general of low scattering intensities which may lead to an equivocal assignment. Hence, the crystallographic analysis of the cubic liquid crystalline phases is not an easy task. Usually rather few reflections are detected because some peaks either are too close together and remain unresolved or are too weak to be observed. To corroborate our analysis, we have repeated the measurements with the very same samples for those of the SAXS diffraction patterns which have

seemed obscure and may be a source of erroneous indexation. The first measurements were done 2 months after the sample preparation (sufficient time for equilibration) and were then repeated 6 months later. The comparison of the SAXS spectra (given in Figure 10) shows that the general appearance of the spectra obtained from one and the same sample may vary over time. Note that the peak at hkl ) 110, which was missing in the P... indexation (respectively hkl ) 200 in the I... indexation) in the first run, appears in the second run. It should be emphasized that the development of this reflection does not influence the indexation. On the contrary, it ensures the correct indexation. Though the cubic lattice was already achieved at the first measurement, the structure continues to “mature” and the systematically missing reflection develops with time probably due to growth of the microcrystals. The binary Pluronic P105-water system was studied previously.8 The SAXS diffraction pattern for composition 40 wt % P105 and 60 wt % water was at that time assigned to a body-centered cubic lattice. This is not in agreement with the preference that we give here to the primitive structure. To body-centered structure has been assigned


Langmuir, Vol. 16, No. 8, 2000 3671

Figure 11. SAXS diffraction pattern obtained for a Pluronic P105-water binary system with composition 40 wt % water and 60 wt % P105 of normal micellar cubic structure, I1.

Figure 10. Comparison of the SAXS diffraction patterns obtained from normal micellar cubic samples, I1, 2 months after sample preparation (denoted as run 1) and 6 months later (denoted as run 2): (top) P105-water binary system with composition of 30 wt % P105 and 70 wt % water; (bottom) P105water-propylene glycol system with composition of 30 wt % P105, 60 wt % water and 10 wt % propylene glycol. The relative diffraction peak intensities are comparable since the spectra were recorded under the same conditions.

also the cubic lattice in the binary P85-water system.42 We have thus measured the SAXS spectrum for composition 40/60 wt % of P105-water (given in Figure 11). There is a very good agreement between the spectra recorded here and that reported some years ago8 with obviously different copolymer batch and probably different preparation and measurement procedures. Furthermore, the value for the lattice parameter obtained considering the I... structure for composition 40/60 wt %, 190 Å, is in very good agreement with the previously reported one, 200 Å.8 Despite the earlier assignment to body-centered lattice, (42) Mortensen, K. J. Phys. Condens. Matter 1996, 8, A103A124.

here we give preference to the primitive lattice for the binary P105-water system as well as for the ternary systems in the presence of glycerol, propylene glycol, and glucose, primarily on the basis of the better agreement of the interfacial area per PEO block with those obtained in the adjacent hexagonal and lamellar phases. The above analysis shows that to be able to assign correctly the cubic lattice, knowledge about the entire phase diagram and the values of the lattice parameter and the interfacial area in the neighboring liquid crystalline phases is necessary. B. Pluronic P105-Water-Glycol Phase Diagrams: Overview. The ternary isothermal (25 °C) phase diagrams of Pluronic P105 in the presence of water and glycol are presented in Figure 3 for four different glycols. A common behavior with respect to the types of the thermodynamically stable structures in which the macromolecules can self-assemble is observed in the four ternary systems studied. An isotropic solution (L1) and three lyotropic liquid crystalline phases, normal (oil-inwater) micellar cubic (I1), normal hexagonal (H1), and lamellar (LR), are established in each of the four systems. In the case of propylene glycol and ethanol, a bicontinuous cubic liquid crystalline phase (V1) is obtained in addition to the L1, I1, H1, and LR microstructures. Along the copolymer-water axis at low (up to 23 wt %) copolymer concentrations, micellar solutions43 are formed. At sufficiently high copolymer concentrations (25-46 wt %) the micelles order and crystallize in a cubic lattice, forming a micellar cubic phase. Further along the copolymer-water axis, a transition to hexagonal packing occurs, i.e., hexagonal liquid crystalline phase is formed between 49 and 68 wt % copolymer, since the cylindrical domains can better accommodate the increased PPO volume compared to the spherical micelles domains. Upon further increase of the copolymer concentration (75-86 wt %), the cylindrical interface becomes also unfavorable and lamellar structure is formed. Above ∼86 wt %, at the copolymer-rich corner of the phase diagrams, nonhomogeneous samples of slightly hydrated copolymer were (43) Alexandridis, P.; Yang, L. Langmuir 2000, in press.

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observed. The microstructure along the copolymer-water axis is depicted schematically in Figure 2. These data are in very good agreement with the previous report on the Pluronic P105-water binary system.8 The sequence in which different phases appear with increasing copolymer concentration is consistent with the concept of the interfacial curvature.5 The interfacial curvature is defined positive when the interface bends toward the apolar domains and negative when the interface bends toward the polar domains.6 The interfacial curvature is zero in the lamellar structure. In a binary block copolymer-selective solvent system, the preferred curvature is initially set by the macromolecular architecture. The Pluronic P105 macromolecule, being symmetric (the ratio of hydrophilic to hydrophobic blocks in P105 is 1:1 in terms of weight), favors the formation of structures of zero curvature (lamellar). The progression of the structure over the phase diagram with decreasing the block copolymer content (increasing the selective solvent content) LR f H1 f I1 f L1 is a consequence of an increase in the interfacial curvature: it changes from zero in the lamellar structure (planar micelles) to positive in the normal hexagonal structure (cylindrical micelles) to highly positive in the normal micellar cubic structure (spherical micelles). The interfacial curvature increases due to an increased swelling (solvation) of the PEO blocks with increasing the solvent content. Reverse (water-inoil) liquid crystalline phases were not obtained in any of the systems studied since the initial preferred curvature of P105 does not favor the formation of reverse structures in the absence of an apolar solvent.5 Such reverse structures in the absence of an apolar solvent (in copolymer-water binary system) have been observed for PEOPPO-PEO block copolymers with low (20 wt %) PEO content.44 The block copolymer (low-right) corner of the phase diagrams is affected by the crystallinity of the PEO block of the copolymer. The glycol (top) corner of the phase diagrams is affected by the solubility of the glycol in water. In all systems studied, the isotropic solution L1 is the most extensive region and expands up to the solubility limit along the water-glycol axis (100 wt % for glycerol, propylene glycol, and ethanol and 60 wt % for glucose). The extent of the L1 solution region decreases in the order ethanol > propylene glycol > glycerol > glucose. The P105-water-ethanol system is notable with respect to the broad solution phase which replaces all liquid crystalline phases at above ∼18 wt % ethanol. The micellar cubic (I1) and the hexagonal (H1) liquid crystalline regions are quite extensive. Their extents vary significantly with the glycol, whereas the lamellar stability region depends less on the type of the glycol (see Figure 3). The hexagonal liquid crystalline phase, for example, can swell with significant amount of glycerol or propylene glycol: up to 2.5:1 parts glycerol per parts water (in terms of weight) and up to 5:1 parts propylene glycol per parts water, respectively. In the case of glucose, this value is 1.2:1 parts glucose per parts water and for ethanol only 0.6:1 parts ethanol per parts water. To the best of our knowledge, such phenomena are reported for the first time and can possibly find practical applications. The presence of normal bicontinuous liquid crystalline cubic phase (V1) in the P105-water-propylene glycol and P105-water-ethanol systems is notable. Bicontinuous cubic phases appear seldom. Of them, V1 seems to be even more scarce. There are only two other reports of V1 (44) Svensson, M.; Alexandridis, P.; Linse, P. Macromolecules 1999, 32, 637-645.

Ivanova et al.

microstructure in PEO-PPO-PEO block copolymer systems: in the Pluronic P84-water5 and the P105-formamide14 binary systems. V1 has also been observed in the Pluronic P105-water binary system in a very narrow region (69-71 wt % P105) and at temperatures below 20 °C.14 It does not appear in the P105-water binary system at 25 °C; instead, it is promoted by the presence of a sufficient amount of propylene glycol or ethanol. The stability region of the bicontinuous cubic phase in the case of propylene glycol is between 65 and 70 wt % P105 and can accommodate from 15 to 25 wt % propylene glycol. In the case of ethanol, V1 exists from 60 to 67 wt % P105 and from 5 to 15 wt % ethanol. The extent of the V1 microstructure in these two systems is comparable; however a lower ethanol than propylene glycol concentration is needed to promote it. In all systems studied, two-phase samples of micellar cubic and hexagonal phases as well as of hexagonal and lamellar phases were identified. Several other two-(three)phase samples are observed (e.g., solution/hexagonal samples, bicontinuous cubic/lamellar samples, and samples consisting of milky precipitate and clear solution). Twophase samples of solution and micellar cubic phases, although expected, were not found in any of the systems studied. The samples of the solution and neighboring micellar cubic phase vary gradually from less viscous at the lowest copolymer concentrations to quite viscous at the highest ones, which sometimes made the discrimination between the two phases difficult. It should be noted that in most cases where it has been detected, the twophase solution/micellar cubic region is quite narrow, e.g.45 The a priori anticipation of such a two-phase region is depicted in the phase diagrams (Figure 3) as a narrow strip. The two- and three-phase regions were not thoroughly examined, which does not allow us to draw the tie-lines in the phase diagrams. Although informative for the phase behavior,46 these details were not studied further since they fall outside our main goal, to capture the general features of the effect of glycols on the Poloxamer phase behavior. Discussion A. Effect of Glycols on the Phase Behavior of PEOPPO-PEO Block Copolymers. A comparison of the effects of the different glycols on the ternary phase behavior of Pluronic P105 (Figure 3) reveals two levels of similarity. At the first level, a similarity is observed between glycerol and propylene glycol in contrast to glucose and ethanol (compare the top and bottom rows in Figure 3) in terms of the extended swelling of the liquid crystalline regions to high glycol/water ratios. Note however, that the lower extent of I1 and H1 in the case of glucose and ethanol can be attributed to different reasons: the low solubility of glucose in water (leading to an immiscibility region due to unfavorable solvency conditions) and the disordering effect of ethanol (favoring the L1 solution region), respectively. The effect of glycols on the degree of swelling of the liquid crystalline phases is much more pronounced for the cubic and hexagonal structures (2.5 and 5 glycol/water wt % ratio for glycerol and propylene glycol versus 1.2 and 0.6 glycol/water wt % ratio for glucose and ethanol), while LR is less affected and extends up to ∼1 glycol/water wt % ratio in all cases. At the second level, a similarity is observed between glycerol and glucose in contrast to propylene glycol and (45) Zhou, D.; Alexandridis, P.; Khan, A. J. Colloid Interface Sci. 1996, 183, 339-350. (46) Laughlin, R. G. The Aqueous Phase Behavior of Surfactants; Academic Press: London, 1994.


ethanol (compare the left and right columns in Figure 3) in terms of swelling of the hexagonal structure to lower copolymer contents with increasing the glycol content, and in terms of the L1-I1 boundary occurring at constant copolymer content (parallel to the glycol-water axis). A similarity is also observed between propylene glycol and ethanol in terms of deswelling of the micellar cubic structure to higher copolymer contents with increasing the glycol content (a bend of the L1-I1 boundary toward the glycol-copolymer axis). The similarity between glycerol and glucose on one hand and propylene glycol and ethanol on the other can also be visualized as a much broader immiscibility region adjacent to the glycolcopolymer axis in the former case than in the latter. This similarity is supported by the different effects of the glycols on the solution region (Figure 3). Both glycerol and propylene glycol are completely miscible with water, but glycerol is relatively more polar than propylene glycol as can be judged by their dielectric constants (see Table 1). The competition between the glycol and PEO blocks of the copolymer for water is much stronger in the case of glycerol than in the case of propylene glycol. As a consequence, the glycerol “solubility” in water decreases (1 wt % P105 decreases it by 10%), while that of propylene glycol remains practically unchanged even at 10 wt % P105. The similarity in the effects of glycerol and glucose opposing those of propylene glycol and ethanol on the phase behavior of P105, described above with respect to the phase boundaries and the immiscibility region, is further reinforced by the appearance of a bicontinuous cubic phase in the cases of propylene glycol and ethanol. Although of limited extent, the appearance of the V1 microstructure is significant for the implication it carries in terms of fluctuations and degree of block segregation. Such bicontinuous structures (intermediate between lamellar and hexagonal) are favored close to the order-disorder transition (weak segregation state).47 Indeed, the V1 structure, though not observed along the P105-water axis, is promoted by the addition of propylene glycol and ethanol but not glycerol and glucose. To investigate more deeply the mechanism of the glycol effects on the ternary phase behavior of PEO-PPO-PEO block copolymers, we have examined below parameters that can be used to describe the ternary phase diagrams studied and their correlation to some physicochemical properties of the glycols. B. Correlation of the PEO-PPO-PEO Block Copolymer-Water-Glycol Phase Behavior to the Glycol Physicochemical Characteristics. The general features of the Pluronic-water-glycol phase diagrams can be captured by two parameters. The first parameter, the water/PEO (hydration) ratio, determines the extent of the liquid crystalline structures toward the block copolymer apex. This ratio does not vary significantly with the glycol type (but may vary with the polymer type because of different PEO content and molecular weight) and for P105 is approximately 0.8 water molecules per EO monomer unit. The second parameter, the highest glycol/water ratio able to maintain the liquid crystalline structures, characterizes the extent of the I1, H1, and LR regions and varies with the glycol type. Although the glycols are all polar and soluble with water, they obviously have different degrees of hydrophilicity. Hence, their different effects can be related to their relative polarity. There are several parameters that can be used as a measure of the glycol polarity, among them are the (47) Bates, F. S.; Schultz, M. F.; Khandpur, A. K.; Fo¨rster, S.; Rosedale, J. H.; Almdal, K.; Mortensen, K. Faraday Discuss. 1994, 98, 7-18.

Langmuir, Vol. 16, No. 8, 2000 3673 Table 5. Octanol/Water Partition Coefficients and Solubility Parameters of the Glycols glycol

octanol/water partition coeff, log Pa

solubility parameter, db (MPa1/2)

glucose glycerol ethylene glycol propylene glycol ethanol

-3.29 -2.55 -1.93 -1.41 -0.32

36.2 33.0 30.2 26.5

a

The data are taken from ref 48. b The data are taken from ref

51.

dielectric constant and the octanol/water partition coefficient. While the dielectric constant is a parameter defining a single physicochemical property, the octanol/ water partition coefficient is a more complex parameter, which encompasses a number of glycol properties. It represents the ratio of the equilibrium concentrations of a given solvent partitioning between the octanol and the water phase.48 The logarithm of this ratio is usually discussed. Data for the dielectric constant of the glycols are given in Table 1. The values of the octanol/water partition coefficients for the glycols used as well as for ethylene glycol as a reference are given in Table 5. The advantages of using the octanol/water partition coefficient as a measure of the glycol polarity rather than simpler parameters, such as the dielectric constant, is in its ability to capture more features related to the solvent polarity, e.g., dipole moment, hydrogen bonding ability, molecular weight. It can also serve as a measure for the hydrophobic interactions in the system, especially widely used in biological and pharmaceutical systems. However, the experimental determination of the octanol/water partition coefficients is subject to errors due to the nature of the system (e.g., processes as ionization, dimerization, or hydrate formation) and the use of different methods.48 The theoretical calculation of the octanol/water partition coefficients also does not always give good predictions because the real systems have nonideal behavior. Lately, computer simulation studies predicting the octanol/water partition coefficients of solvents based on a quantitative structure-property relationship approach have been reported.49 Another complex parameter that can be used to describe the interactions in the system is the solubility parameter. It is commonly used in the physical chemistry of polymers to characterize the affinity of a polymer to a given solvent. The solubility parameter is related to the cohesive energy density and can be used to provide an estimate for the χ Flory-Huggins interaction parameter.50 To minimize the enthalpy of mixing in the system, a wide-spread and convenient approach is choosing the best solvent for a polymer based on the solubility parameter. However, it can fail when specific interactions occur in the system, e.g., hydrogen bounding. To improve the accuracy of the prediction, Hansen51 has introduced the so-called threedimensional model according to which the overall solubility parameter is represented as a sum of individual contributions for the dispersive, polar, and hydrogen bounding interactions in the system. In our discussion we have used the values for the solubility parameters of the glycols reported by Hansen51 (see Table 5). (48) Leo, A.; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525-616. (49) Huuskonen, J.; Villa, A.; Tetko, I. J. Pharm. Sci. 1999, 88, 229233. (50) Fried, J. R. Polymer Science and Technology; Prentice Hall: Englewood Cliffs, NJ, 1995; Chapter 3. (51) Hansen, Ch. Handbook of Surface and Colloid Chemistry; Birdi, K. S., Ed.; CRC Press: New York, 1997; Chapter 10.

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Figure 12. Correlation between the highest glycol/water ratio (expressed as molar parts) able to maintain the stability of the liquid crystalline structures and the relative polarity of the glycols expressed in terms of (top) the octanol/water partition coefficient, log P, (middle) the dielectric constant, , and (bottom) the solubility parameter, δ. The lines are drawn as a guide to the eye.

We thus have examined the correlation between the highest glycol/water ratio able to maintain the stability of the liquid crystalline phases and the relative polarity of the glycols, expressed in terms of their octanol/water partition coefficient, dielectric constant, or solubility parameter (Figure 12). The dielectric constants of the glycols as well as their octanol/water partition coefficients and solubility parameters show that the relative polarity of the glycols increases in the order: ethanol < propylene glycol < glycerol < glucose. The extent of the L1 solution region decreases in the same order. The non-monotonic trends revealed in Figure 12 suggest that there are “optimal” glycols where maximum extent of the liquid crystalline phases can be achieved. Propylene glycol possibly belongs to this group.

Ivanova et al.

C. Hypothesis for the Role of Glycols, Based on their Relative Polarity. The correlations demonstrated between the effect of the glycols on Pluronic phase behavior in water and their octanol/water partition coefficients, dielectric constants, or solubility parameter indicate that the relative polarity of the cosolvents (glycols) plays an important role in determining the block copolymer phase behavior in selective solvents. As seen from Table 5, the logarithms of the octanol/water partition coefficients of the glycols are negative. Ethylene glycol has the closest structure to the PEO segments of the copolymer and log P ) -1.93, whereas propylene glycol is closest to the PPO segments and its log P ) -1.41. Thus, while both are polar, propylene glycol is relatively more hydrophobic than ethylene glycol. If we assume the relative polarities of poly(ethylene oxide) and poly(propylene oxide) to follow those of ethylene glycol and propylene glycol, respectively, then we can classify further the glycols as PEO- or PPOresembling, on the basis of their octanol/water partition coefficients. PEO-resembling glycols have log P lower than that of ethylene glycol and will have preference to locate in the polar microdomains, the same that the PEO segments of the copolymer and water occupy. PPO-resembling glycols have log P higher than that of propylene glycol and will have a preference to locate in the apolar microdomains, the same as the PPO segments. Therefore PEO- and PPOresembling glycols will exhibit different effects on the phase behavior of the copolymer. Of the glycols examined here, ethanol has log P higher than that of propylene glycol, while glycerol and glucose have log P lower than that of ethylene glycol (Table 5). Therefore, ethanol and propylene glycol are expected to exhibit similar effects on Pluronic phase behavior, which should be opposite to those of glycerol and glucose. Indeed, this hypothesis is corroborated by the similarities in the experimental results discussed in section A. The symmetric Pluronic P105 macromolecule favors the formation of planar structures at high copolymer content along the copolymer-water axis. When the copolymer content is lowered (i.e., at higher water contents), structures with higher curvature (cylindrical or spherical) are formed. When glycerol or glucose is added, it occupies the polar domains of the microstructure but does not contribute to the swelling of the PEO blocks as evidenced by the decrease of the preferred curvature (preference of hexagonal over cubic structure) at higher glycol content. When propylene glycol or ethanol is added, it swells both PEO and PPO blocks as is evidenced by the constant preferred curvature in the system (phase boundaries being at constant copolymer content). At the same time, a PPOresembling glycol together with water provides better solvency conditions for the whole macromolecule and broadens the miscibility region. This peculiarity of the P105-water-ethanol system was already emphasized. The effect of weakening the block segregation, which is induced by water (a solvent selective for the PEO blocks but not for the PPO block), by PPO-resembling glycols can also explain why only propylene glycol and ethanol but not glycerol and glucose provide the requirements necessary to promote bicontinuous cubic phase. The trends in the effect of glycols on Pluronic phase behavior (macroscopic aspects) predicted by this hypothesis are furthermore confirmed and quantified by the systematic SAXS investigation of the glycol effects on the liquid crystalline microstructure analyzing their characteristic length scales (microscopic aspects).32 As we have previously shown,5,9 the interfacial curvature which is initially set by the macromolecular architecture


can be further modified by the ability of the copolymer blocks to swell to a different degree with selective solvents (water and/or oil). Here, we demonstrate that modification of the preferred curvature can also be achieved by polar cosolvents (glycols) with different degree of polarity. The phase diagrams of the systems studied, however, are dominated by structures with high preferred curvature: micellar solution, micellar cubic, and hexagonal liquid crystalline phases. Although with different degree of polarity, all glycols are polar and therefore unable to promote reverse structures in the symmetric P105 macromolecule, and thus the interfacial curvature remains predominantly positive. To reverse the interfacial curvature to negative, the presence of an apolar cosolvent (oil) with strong tendency to swell the PPO block would be necessary.5,10 Conclusions The effect of glycols as polar cosolvents on the phase behavior of poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronics) in water has been elucidated. Four glycols with different relative polarities are examined: glycerol, propylene glycol, ethanol, and glucose. The microstructure of the liquid crystalline “gel” phases has been established analyzing the SAXS diffraction patterns obtained in each phase. The block copolymer can self-assemble in four different thermodynamically stable structures in the presence of all glycols studied. Along the copolymer-water axis, at copolymer concentrations up to 25 wt %, isotropic solutions are formed. With increasing the copolymer content, normal micellar cubic, normal hexagonal, and lamellar lyotropic liquid crystalline phases occur consecutively. A normal bicontinuous cubic liquid crystalline phase is obtained in addition to the micellar cubic, hexagonal, and lamellar structures in the cases of propylene glycol and ethanol. The crystallographic structure of the micellar and bicontinuous cubic phases is established, consistent with primitive cubic lattice and Ia3d Gyroid space group, respectively. In the case of ethanol (in the concentration range studied), the micellar cubic lattice is assigned to a different crystallographic space group, Pm3n. A pronounced effect of the glycol type on the concentration range of stability of the different lyotropic liquid crystalline structures in the systems studied was found.

Langmuir, Vol. 16, No. 8, 2000 3675

A similarity in the effects of glycerol and glucose opposing those of propylene glycol and ethanol in terms of swelling of the hexagonal structure to lower copolymer contents with increasing glycol content is found. This similarity is further reinforced by the appearance of a bicontinuous cubic phase in the cases of propylene glycol and ethanol. The presence of bicontinuous cubic structure only in these two systems is significant with respect to its scarce appearance, the intricate microstructure (with potential in practical applications), and the implication it carries in terms of fluctuations and degree of block segregation. A conclusion that certain glycols, depending on their physicochemical properties, can alter the degree of block segregation in the macromolecule is inferred. We have correlated the highest glycol/water ratio able to maintain stability of the liquid crystalline phases to the relative polarity of glycols, expressed in terms of the octanol/water partition coefficient, the dielectric constant, or the solubility parameter. A hypothesis is proposed, based on the cosolvent degree of hydrophilicity, and the results obtained, to account for and predict the effect of cosolvent type on the ternary phase behavior of Pluronics. The interfacial curvature initially set by the macromolecular architecture can be modified by the ability of the cosolvents to swell different blocks of the macromolecule. The direction in which different cosolvents act will depend on the cosolvent hydrophilic/hydrophobic character. Thus the self-assembly behavior of Pluronics can be modulated in the desired direction. 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 Petroleum Research Fund (Grant ACSPRF#33408-G7) and the National Science Foundation (Grant CTS-9875848). The acquisition of the SAXS apparatus was funded by the Swedish Council for Planning and Coordination of Research (FRN). LA991235V

Effect of Glycols on the Self-Assembly of Amphiphilic Block

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