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Nonideality in Mixed Monolayers of Sorbitan Oleates Is Enhanced by Elevated Ionic Strength Dongmei Lu, Diane J. Burgess, and David G. Rhodes* Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269-2092 Received July 25, 2000. In Final Form: October 11, 2000 Mixtures of sorbitan fatty acid esters and the analogous polyoxyethylene adducts are often used to stabilize emulsions. However, the phase behavior of these mixtures is not clearly understood. In addition, the properties of films of these surfactants depend on solvent conditions. Previous results for mixtures of polyoxyethylene sorbitan monoleate with sorbitan monooleate, sorbitan sesquioleate, or sorbitan trioleate showed that these surfactants form nonideal mixtures at the air-water interface. In the work reported here, similar films have been investigated with high ionic strength subphases. Nonideality observed with monooleate- and sesquioleate-containing films is enhanced at elevated ionic strength. For mixed films containing sorbitan trioleate and polyoxyethylene sorbitan monoleate, condensation is observed for films of nearly equimolar composition. A model to explain this behavior is based primarily on molecular shape complementarity.
Introduction Sorbitan esters are important nonionic surfactants with applications in pharmaceuticals, cosmetics, environmental engineering, chemical processing, and many other areas. Among the most widely used surfactants are the Span family of fatty-acylated sorbitan esters and the analogous polyoxyethylene (POE) derivatives (Tweens). These have been used to improve the stability of water-in-oil-in-water (W/O/W) multiple emulsions,1-3 with the relatively hydrophobic Spans used to stabilize the W/O emulsions and the more hydrophilic Tweens used to stabilize the O/W emulsions.4,5 The ability of these surfactants to adsorb to an oil-water interface and form a stable layer is essential for stable emulsion formation.6,7 It has been shown that the rheological properties of Span and Tween films at the oil-water interface depend on properties of the aqueous phase such as temperature and ionic strength. In studies of films at the mineral oil/ water interface, Opawale and Burgess showed that interfacial elasticity of Span 80 and Span 83 decreased with increasing ionic strength.8 Further, they found that W/O emulsion stability decreased with increased ionic strength, indicating a relationship between interfacial elasticity and emulsion stability. In a previous report, we described the phase behavior of mixed films of Tween 80 and Spans 80, 83, and 85 at the air-water interface. The mixing was generally nonideal, but the surfactants did appear to be at least partially * To whom correspondence should be addressed. Phone: 860486-5413. Fax: 860-486-4998. E-mail:
[email protected]. (1) Mishra, B.; Pandit, J. K. J. Controlled Release 1990, 14, 53. (2) Omotosho, J. A.; Whateley, J. L.; Florence, A. T. J. Microencapsulation 1989, 6, 183. (3) El-Nokaly, M.; Hillwe, G.; McGrady, J., In Mocroemulsions and Emulsions in Foods; El-Nokaly, M., Cornell, K., Eds.; ACS Symposium Series 448; American Chemical Society: Whashington, DC, 1991; p 26. (4) Wheatley, M. A.; Peng, S.; Singhal, S.; Goldberg, B. B. United States Patent 5352436, 1994. (5) Florence, A. T.; Whitehill, D. J. Pharm. Pharmacol. 1982, 34, 687. (6) Ruckenstein, E.; Park, J. S. Polymer 1992, 33, 405. (7) Rosen, M. J. Surfactants and Interfacial Phenomena, 2nd ed.; Wiley: New York, 1989. (8) Opawale, F.; Burgess, D. J. J. Colloid Interface Sci. 1998, 197, 142.
miscible. Mixtures of Tween 80 and Span 85 for low mole fractions of Tween 80 appeared to be more ideal and excess area analysis exhibited apparent condensation.9 This was presumed to be due to the steric compatibility of these molecules: one largely hydrophobic with a small hydrophilic group and the other with a small hydrophobic moiety and water-soluble, oligomeric substituents in the headgroup. The mixing of Tween 80 with Spans 80, 83, and 85 apparently involved a balance of hydrophilic and hydrophobic interactions and steric factors. It was not clear how changes in the properties of the aqueous subphase would affect the stability of these films or their mixing behavior. Published work on the effects of electrolytes on the stability of films at the oil-water interface reflects some controversy.10-12 Some reports indicate that electrolytes rigidify these interfacial films,10 while others suggest that the presence of salts facilitates breakdown of the film.8,11,12 We report here work with similar mixed films using a subphase with higher ionic strength in order to evaluate whether the effects seen previously at the oil-water interface are also seen at the air-water interface. Materials and Methods Materials. Surfactants (shown in Chart 1) included Span 80 (Sorbitan monooleate), Span 83 (Sorbitan sesquioleate), Span 85 (Sorbitan trioleate), and Tween 80 (polyoxyethylene sorbitan monoleate). All were obtained from Sigma-Aldrich and used without further purification. Chloroform, HPLC grade, was purchased from Fisher Scientific. Deionized distilled water (>18 MΩ cm) was used for all experiments. Span and Tween stock solutions were prepared gravimetrically in chloroform. Mixtures of Span and Tween at specific mole fraction concentrations were also made by gravimetric measurements. Monolayers. Compression isotherms were obtained by protocols similar to those reported previously, using a KSV “Minitrough” Langmuir film balance. The Teflon trough was filled with 0.1 M NaCl as the subphase to approximately 1 mm below the edge. The surface was cleaned by rapid compression with the Delrin barriers, followed by aspiration of the compressed surface (9) Lu, D.; Rhodes, D. G. Langmuir 2000, 16, 8107. (10) Brodin, A. F.; Kavaliunas, D. R.; Frank, S. G. Acta Pharm. Suec. 1978, 15, 1. (11) Masumoto, S.; Sherman, P. J. Texture Stud. 1981, 12, 243. (12) Oza, K. P.; Frank, S. G. J. Dispersion Sci. Technol. 1989, 10, 163
10.1021/la001058u CCC: $19.00 © 2000 American Chemical Society Published on Web 11/29/2000
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Chart 1. Structures of Surfactantsa
Figure 1. Compression isotherms of Span 80 (a), Span 83 (b), and Span 85 (c), and Tween 80 (d). Bold lines are for a 0.1 M NaCl subphase and the thin lines are on pure water.
a Span 80 (a) is a sorbitan monooleate. Span 83 is a mixture of sorbitan monooleates (a) and dioleates (b). Span 85 is a sorbitan trioleate (c). Tween 80 (d) is a monooleate with a POE -substituted headgroup. The distribution of POE units is random, but the number shown in this representative structure is correct.
if any significant increase (g1 mN/m) in surface pressure, π, was observed. Surfactant (18.67 nmol in chloroform) was deposited onto the subphase using a digital Hamilton microsyringe. The chloroform was allowed to evaporate for 20 min prior to compression. Isotherms. Compression isotherms (surface pressure, π, as a function of molecular area, A) were obtained using symmetric compression at a constant gradient of surface pressure (dπ/dt ) 1.0 mN/(m/min)). In addition, a maximum linear barrier speed of dx/dt ) 5 mm/min (750 mm2/min) was used. An etched platinum Wilhelmy plate was used to measure π. Isotherms were run in triplicate (freshly prepared monolayers and subphase). All measurements were made at 20.0 ( 0.1 °C. Excess Area Analysis. The molecular excess area, AE, for a mixed film consisting of mole fractions X1 and X2 of the two components, is defined at specified π as
AE ) A12 - (X1A1 + X2A2) where A1, A2, and A12 are mean molecular areas of the individual components and the mixed monolayer at the specified π.13 For mixed films which exhibit either ideal mixing or complete immiscibility, AE ) 0. Nonzero AE reflects nonideal behavior of miscible systems, with positive AE indicating repulsion and negative AE indicating condensation. It should be emphasized that compression isotherms are not, strictly speaking, equilibrium measurements. Thus, as with all compression measurements, the measured molecular area depends on conditions such as compression rate. However, because temperature and compression protocol were identical for all of the data discussed here, the phase behavior of the films can be compared and the effects of variables such as ionic strength analyzed in detail.
Results Compression Isotherms. Compression of the pure components on a 0.1 M NaCl subphase showed that each formed a stable film (Figure 1). Tween compression isotherms were almost identical to those obtained on a pure water subphase.9 The compression isotherms of Span 80 on the higher ionic strength subphase were more expanded than similar isotherms on pure water (Figure 1). At low π, compression isotherms of Span 83 on a high (13) Gaines, G. L., Jr. Insoluble Monolayers at the Liquid-Gas Interfaces; Wiley-Interscience: New York, 1996.
ionic strength subphase were more expanded than those on pure water, but at π > 7 mN/m the isotherms on pure water were more expanded. Compression isotherms of Span 85 on a high ionic strength subphase were more condensed than those on pure water, but the maximum π was significantly lower. The extrapolated molecular area was highest for Span 85 (>100 Å2) and lowest for Span 80 (30 Å2). It was not possible to determine an extrapolated molecular area for Tween 80 due to the shape of the isotherm and the likelihood that Tween 80 was being forced into the subphase. The ionic strength (0.1 M) was chosen based on elasticity measurements by Opawale and Burgess,8 in which 0.1 M NaCl was sufficient to have significant effects on the interfacial rheology of Span and Tween films. Mixed Composition Films. The overall compression behavior of mixed composition films was similar to that observed with films of corresponding composition on a water subphase. In most cases, mixtures of Tween 80 with Span 80 or Span 83 produced more expanded films on a higher ionic strength subphase (Figure 2). In contrast to the discontinuities or phase transitions observed for some mixtures of Tween 80 with Span 80 or Span 83 on a pure water subphase,9 no apparent coexistence regions indicative of phase transitions were observed on the higher ionic strength subphase. At low mole fraction Tween 80 (XT80), mixed films of Tween 80 and Span 85 on a 0.1 M NaCl subphase were more condensed than similar films on pure water (Figure 2). At higher XT80, however, isotherms of mixed composition films were quite similar. Nonideal Behavior. In mixed composition films, the mean molecular area varies linearly with composition if the mixing is ideal or if the components are immiscible. Nonideality, by analogy to that observed in colloidal solutions, can be in the form of excluded area (positive deviation) or condensation (negative deviation). Data from mixtures of Tween 80 and Span 80, Span 83, or Span 85 on a 0.1 M NaCl subphase generally exhibited positive deviations (Figure 3a-c) as observed previously with pure water. For Span 80 and Span 83 containing mixtures, the nonideality was significantly greater with the higher ionic strength subphase. For Tween 80-Span 85 mixtures, the behavior was more complex. Plots of mean molecular area at specific surface pressures as a function of XT80 exhibited a minimum at XT80 ) 0.5 but positive deviations for other mixtures. Excess Area Analysis. Molecular excess area calculations clearly demonstrate that the mixing behavior of Tween 80 mixtures with Span 80 or Span 83 is more nonideal on 0.1 M NaCl than on pure water (Figure 4 a,b). The overall relationships are similar, but no transitions
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Figure 2. Compression isotherms for mixtures of Tween 80 with Span 80, Span 83, or Span 85 for several compositions from XT80 ) 0.1 to XT80 ) 0.9. Bold traces are for films on 0.1 M NaCl and thin traces are for films on pure water.
Figure 3. Mixing behavior for mixtures of Tween 80 with Span 80 (a), Span 83 (b), or Span 85 (c) represented as the mean molecular area at a given surface pressure, π. Traces correspond to π ) 5 (9), 10 (b), 15 (2), and 20 mN/m ([). Data for 15 mN/m are eliminated from a and b for clarity. Bold traces are for films on 0.1 M NaCl, and thin traces are for films on pure water.
are observed in the data from experiments with 0.1 M NaCl subphases. Molecular excess area for Span 85Tween 80 mixtures shows that there is condensation for specific compositions, especially at a surface pressure of approximately 12 mN/m (Figure 4c). Differences in the AE results obtained for Span 85-Tween 80 mixtures compared to those obtained with Span 80 or Span 83 are most pronounced at high pressures. Discussion The stability of mixed films can be markedly different from that of either of the constituents. Through steric,
ionic, or other interactions, additional surfactants can stabilize or destabilize a film and thus alter measurable properties such as collapse pressure, elasticity, viscosity, or molecular area at a given surface pressure.6,14-16 It is known that Tween surfactants can alter the rheological properties of Span films and that these effects depend on the aqueous phase conditions (ionic strength, temperature, (14) Rosen, M. J.; Murphy, D. S. Langmuir 1991, 7, 2630. (15) Rajagopalan, V.; Bagger-Jorgensen, H.; Fukuda, K.; Olsson, U. Langmuir 1996, 12, 1239. (16) Opawale, F.; Burgess, D. J. J. Pharm. Pharmacol. 1998, 50, 965.
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Figure 4. Excess area (AE) analysis for mixtures of Span 80 and Tween 80 (a), Span 83 and Tween 80 (b), and Span 85 and Tween 80 (c). Traces in each graph are for XT80 ) 0.1 (9), 0.3 (2),0.5 (0), 0.7 (4), 0.9 (/). Dashed lines indicate the range of data for films on pure water subphases.
etc.).16 The purpose of this work was to determine the effect of elevated ionic strength on the mixing behavior of Tween 80 and several Span surfactants. Addition of NaCl can alter the hydrophilicity-lipophilicity balance (HLB) of surfactants. It was previously reported that preferential hydration of the ions over the surfactant headgroups reduces the interaction of water with the surfactant.17 Although many salting out effects require very high ionic strength, Opawale and Burgess8,16 showed that 0.1 M NaCl was sufficient to alter the rheological properties of Span and Tween films. In general, increased ionic strength decreases the aqueous solubility of hydrophobic entities,18 and consequently, the stability of aqueous-soluble surfactant films would be expected to increase. This has been explained in terms of a “salting out” of the surfactant from the aqueous phase and demonstrated experimentally for protein surfactants.19,20 By contrast, the stability of oilsoluble surfactant films at an oil-aqueous interface might be expected to decrease with ionic strength, as a result of dehydration of the headgroup. The interfacial elasticity of Span films at the oil/aqueous interface has been shown to decrease with increased ionic strength.8 At an air-aqueous interface, the decreased solubility of hydrophobic moieties with increased ionic strength could increase the surface pressure of a surfactant film. The ability of the aqueous subphase to accommodate acyl chains at low surface pressure would be decreased. This effect would correspondingly increase the area at the interface that would be occupied by the molecule, resulting in higher surface pressure. For films of ionic surfactants such as monoalkyl fatty acids or amines, the dominant interaction is the long-range repulsion of the charged headgroups. Therefore, molecular area would be expected to decrease with increased ionic strength. For nonionic surfactants, this effect is not present, but the influence of ionic strength on acyl chain solubility might be reflected in the compression behavior. In this work, compression isotherms of Span 80 and Span 83 exhibited increased molecular areas at elevated ionic strength for low π. Tween 80 isotherms exhibited negligible dependence on ionic strength, and Span 85 films were more condensed on a high ionic strength subphase (17) Kawashima, Y.; Hino, T.; Takeuchi, H.; Niwa, T. Chem. Pharm. Bull. 1992, 40, 1240. (18) Standal, S.; Blokhus, A.; Haavik, J.; Skauge, A.; Barth, T. J. Colloid Interface Sci. 1999, 212, 33. (19) Burgess, D. J.; Sahin, O. N. Pharm. Dev. Technol. 1998, 3, 21. (20) Burgess, D. J.; Sahin, O. N. J. Colloid Interface Sci. 1997, 188, 74.
on pure water. To interpret these data, consider the molecular cross-sectional area of the various surfactants in condensed films. For single-chain surfactants, the minimum molecular area of the hydrophobic moiety should be approximately 20-25 Å2, and proportionately higher areas should be observed for surfactants with two or three chains. Unsaturated chains have higher areas than the corresponding saturated chains but at moderate surface pressures can form stable films. The predicted area of a hydrophilic sorbitan headgroup depends on the orientation of this moiety, but a simple estimate with a molecular graphics program (not shown) suggests an area of approximately 40 Å2. For compression of a film of Span 80, therefore, the headgroup interaction will dominate the minimum molecular area before the chains are able to do so. In other words, at the point where the headgroup interaction results in high surface pressure, the oleate chains will still be disordered and will not contribute to film stability. For a film of Span 83 (which is a mixture of monooleate and dioleate in a 2:1 ratio), the mean chain area per molecule would be approximately 30 Å2. Therefore, the headgroup interaction could still be a significant factor, especially at higher π. The trioleate, Span 85, has a very large hydrophobic area, so molecular interactions would be dominated by acyl chain interactions. Tween 80 has a very large headgroup with three independent POE chains and only a single acyl chain, so the dominant interactions would be between POE chains in the subphase. On a pure water subphase, Span 80 interactions are dominated by headgroup interactions at the air/water interface, so decreasing acyl chain solubility by increasing ionic strength (and thus, increasing the area at the surface occupied by the acyl chain) increases the molecular area for Span 80 films. Nevertheless, the chains are still not sufficiently dense, relative to the packed headgroups, to achieve cooperative van der Waals interactions. A similar effect is observed for Span 83, but some cooperative interaction may be possible at higher π. In the case of Span 85 films, where hydrophobic interactions are already favorable, decreasing the water solubility of the acyl chains by increasing ionic strength enhances cooperative interchain interaction. In the case of Tween 80 films, interaction between acyl chains is so unlikely that altering the solubility of the acyl chains has little effect. The solubility of POE would also be expected to decrease with increased ionic strength,17 but this would not be enough to force the POE chains from the subphase. One possible consequence would be to encourage condensation of the POE chains; however these results (Figure 1) suggest that at this ionic strength, the effect is minimal.
Nonideality in Mixed Monolayers
Figure 5. Mixed monolayers of Span (S) and Tween (T). The sketch is intended to reflect relative molecular bulk for different numbers of acyl chains and POE substituents. Span 80 (monooleate) is shown at high (0.5) XT80 (left) and at low XT80 (right). Span 83 (a 2:1 mixture of monooleate and dioleate) is shown at low XT80 ) 0.25. Span 85 (trioleate) is shown at XT80 ) 0.5.
Mixed composition films follow this general trend. For films with Span 80 or Span 83 at low XT80, the films on 0.1 M NaCl subphases are more expanded than those on pure water. In contrast, Span 85 containing films on pure water are more expanded than those on high ionic strength subphases. For all three Spans studied here, differences between films on high ionic strength subphases and those on low ionic strength subphases are minimal at high XT80, presumably due to the dominance of Tween 80 steric interactions in the aqueous side of the interface. The model shown in Figure 5 illustrates these effects. At high XT80 (J0.5) molecular packing at the surface is dominated by Tween 80/Tween 80 interactions (Figure 5a, left side). Even at lower XT80 (Figure 5a, right side) the packing is headgroup-dominated, and the Span 80 film is not stabilized by the addition of Tween 80. The situation is similar for mixed films of Tween 80 and Span 83 (Figure 5b). We suggest that for the water-soluble surfactant, Tween 80, films of Span 80 or Span 83 may facilitate adsorption of Tween to the interface. However, favorable interactions are weak and steric repulsion makes the mixture highly nonideal because all surfactants in the system have large headgroup areas relative to the hydrophobic areas. The increase in nonideality with increased ionic strength could arise from decreased solubility of the hydrophobic moieties and the slightly higher surface activity of Tween 80. Films of Span 85, however, are area-deficient in the region of the headgroup, so molecules with large head-
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groups could complement these structures. Span 85 has three oleate chains and Tween 80 has three POE chains not terminated by an alkyl substituent. Therefore, if each molecule were tightly and stably packed in a constrained monolayer, one could envision that these molecules could have approximately equal molecular areas (Figure 5c), corresponding to three times the area of a single chain. In such a film, however, one molecule would have a larger area in the aqueous subphase and the other a larger area in the air phase. At a 1:1 ratio, the hydrophobic and hydrophilic areas could be comparable, and very efficient packing could occur. As shown in Figure 3c, this is seen as a relative condensation of the mixed composition films on a 0.1 M NaCl subphase. At other XT80, the complementarity is less well established, and nonideal mixing is observed. That this condensation is not observed with pure water subphase could be due to either POE condensation as a result of higher ionic strength or decreased acyl chain solubility. If the areas of POE chains were too large in pure water, but could be condensed at higher ionic strength due to decreased POE solubility, Tween 80-Span 85 mixing could be facilitated by added salt. The similarity of the area/composition curves at high XT80 (Figure 3c) suggest that differences between Tween 80 in pure water and Tween 80 in 0.1 M NaCl are minor, even in mixtures with Span 85. An alternative model, based on decreased acyl chain solubility due to higher ionic strength, supposes that increasing the tendency for acyl chains to be out of the aqueous phase could result in more order among the Span 85 acyl chains. These could then stabilize the Tween 80 acyl chain more easily. This model is supported by the curves at low XT80 in Figure 3c, which indicate repulsion nonideality. Condensation might occur at lower XT for Tweens with smaller POE moieties or at larger XT for Tweens with more extensive POE moieties. On the basis of these observations, we expect that mixed films of Span 85 and Tween 80 should be more stable than homogeneous films. At XT80 0.5, it is possible that in-plane heterogeneity exists, in which stable equimolar domains would be established within less stable regions composed principally of one component or the other. This speculation remains to be demonstrated experimentally. It is also clear that the mixing behavior of surfactant films at the airwater interface has significant dependence on ionic strength, even for nonionic surfactants. These results may be of value in choosing aqueous solvent conditions for emulsions. Acknowledgment. This work was supported, in part, by a grant from the National Institutes of Health (GM55973; D.G.R.), by the University of Connecticut Research Foundation (D.G.R., D.J.B.), and by support from Pharmacia and Upjohn, Inc. (D.J.B.). LA001058U
