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Formation of liquid crystals in sunflower oil in water emulsions
Formation of Liquid Crystals in Sunflower Oil in Water Emulsions N. PILPEL ~ AND M. E. RABBANI 2 Chelsea Department of Pharmacy, Kings College(KQC), Universityof London, Manresa Road, London SW3 6LX, UnitedKingdom
Received October 9, 1986; accepted December 9, 1986 Sunflower oil in water emulsions containing between 10-70% (w/w) oil and 1-15% (w/w) sorbitan monopalmitate (Span 40) and polyoxyethylene(20) sorbitan monopalmitate (Tween 40) in different ratios were prepared. Their rheological behavior was investigated by continuous shear rheometry and by creep viscometry.Emulsions containing >-5%(w/w) of Span/Tween in weight ratios of 6/4 and 7/3 exhibited viscoelasticity.This was ascribed to the presence of a lamellar type of liquid crystalline phase in the systemswhich was confirmed by electron microscopy. © 1987AcademicPress,Inc. INTRODUCTION
also presented which support the theory of stabilization of emulsions by a liquid crystalline phase. Knowing the molecular dimensions of the two emulsifiers employed it should, in principle, be possible to decide whether the liquid crystalline phase is of hexagonal, reversed hexagonal, or lamellar type (12-14).
The stability of viscoelastic emulsions prepared by using a mixture of a lipophilic and a hydrophilic emulsifier (such as Span and Tween) in high concentrations has been attributed to the formation of three-dimensional association structures of liquid crystals by Friberg and co-workers (1-5). Direct evidence for EXPERIMENTAL their presence and location has been obtained by optical and electron microscopic techMaterials. The oil used was an edible grade niques (4-7). Rheological measurements m a y also pro- of refined dewaxed sunflower seed oil (Alembic vide some indirect information about the Products, n 2° 1.475; d42° 0.9334; viscosity 100 cp at 20°C). The emulsifiers were samples of structure of the systems (8, 9). In the present work oil in water emulsions Span 40 (sorbitan monopalmitate) and Tween containing Span 40/Tween 40 in different ra- 40 (polyoxyethylene (20) sorbitan monopaltios and covering a wide range of concentra- mitate), supplied ~98.5% pure by Atlas tions were investigated by employing both a Chemicals. The water was distilled from an continuous shear rheometer and a variable all-glass still (surface tension 72.0 + 0.2 m N stress rheometer (in creep tests). Viscoelastic m -~ at 20°C, specific conductivity at 20°C, parameters were calculated and used to derive 1.4 × 10 -6 o h m -1 cm-1; p H 5.8 _+ 0.1). Methods. Oil in water emulsions were prethe structure of the systems on the basis of a pared containing 10-70% (w/w) oil and l-15% mathematical model for the viscoelastic (w/w) total emulsifier with the ratios of Span/ emulsions developed by Oldroyd (10, 11). Tween between 1/9 and 9/1 (w/w). The comSome new electron microscopic data are ponents were weighed out, heated to 45°C mixed with a mechanical stirrer for 5 min, and then cooled slowly and stored at 20°C in glass1To whom correspondence should be addressed. 2 Present address: Department of Pharmacy, Bahauddin stoppered bottles. Droplet sizes were measured Zakariya University, Multan, Pakistan. on a Coulter Model TA 11 counter (Coulter 550 0021-9797/87 $3.00 Copyright © 1987 by Academic Press, Inc. All rights of reproduction in any form reserved.
Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
FORMATION OF LIQUID CRYSTALS IN EMULSIONS Electronics) and expressed as mean volume surface diameters. Rheological examination. Samples were subjected to continuous shear at 20°C in a Ferranti-Shirley cone and plate viscometer using a 70-mm-diameter cone, a 1200 g cm torque spring, and an automatic gap setting device with a clearance of 2.5 ~m. The instrum e n t was operated at a m a x i m u m of 50 r p m and a sweep time of 60 s producing a maxim u m shear rate of 832 s-1. Rheograms of three replicates were plotted automatically and the areas of the hysteresis loops were determined with a planimeter, the scale expansion being dependent on the sample. Samples which exhibited spurs on the ascending curves of their rheograms were subjected to creep tests. The creep compliance behavior for the first 24 h after preparation was measured at 20°C with a concentric cylinder air turbine viscometer as discussed more fully elsewhere (15-17), and the data were analyzed graphically. Electron microscopy. Selected samples were frozen in slushed nitrogen at - 2 1 0 ° C and fractured at - 1 3 5 ° C under a v a c u u m of 1 N 10 -6 T o r t using a Polaron E7500 freeze fracture unit. Replicates were obtained by shadowing first with a platinum/carbon mixture at 45°C and then with carbon at 90 ° and were used to obtain electron micrographs at various magnifications with a Philips EM301G transmission electron microscope. For details of the technique, see Refs. (18, 19). RESULTS Figure 1 shows typical droplet size distribution plots of the freshly prepared emulsions. The m e a n droplet size depended on the concentration of oil and emulsifier and on the ratios of Span/Tween. It was m i n i m u m when the total emulsifier concentration was 10% (w/ w) and the ratio of Span/Tween was 6/4. Emulsions with >/5% (w/w) emulsifier exhibited non-Newtonian pseudo-plastic flow with hysteresis. The areas of the hysteresis loops increased with the increasing concentration of emulsifier, Table I, and were also af-
551
30
25
2O
o~
< 6
7
Droplet diameter (IJm)
FIG. 1. Droplet sizedistribution of emulsions containing 40% (w/w) oil and 10% (w/w) emulsifier. Span/Tween ratios, 3/7 (It), Span/Tweenratios4/6 (A), Span/Tweenratios 6/4 (O), Span/Tween ratios 7/3 (0).
fected by the concentration of oil and by the ratio of Span/Tween reaching a m a x i m u m at a ratio of 6/4 (w/w). Spurs occurred on the up curves of the rheograms in systems containing 20-50°70 (w/w) oil and >~5% (w/w) Span/Tween in the ratios of 6/4 and 7/3 only. The apparent viscosities (napp) of the samples at the m a x i m u m shear rate of 50 × 16.63 s-l, i.e., the viscosities of the Newtonian fluids which would show the same shear stress at this rate, are plotted typically against oil contents in Fig. 2, and against the total emulsifier contents and ratio in Fig. 3. napp increased with oil content and with total concentration of Span/Tween in any ratio but this increase became steeper with 5% (w/w) Span/Tween present in the 6/4 and 7/3 (w/w) ratios. The systems giving spurs in their rheograms exhibited viscoelasticity under the test conditions imposed. The viscoelastic parameters of the emulsions were derived from analysis of the creep curves by graphical methods (2022). Table II, typically summarizes the parameters derived from these curves. It is seen that the creep behaviors of the emulsions containing 30-40% (w/w) oil were characterized by six parameters. These are Eo, an instantaneous elastic modulus; El, E2, retarded elastic Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
552
PILPEL AND RABBANI TABLEI
Areas of the HysteresisLoops of Emulsions Containing 40% (w/w) Oil and Various Concentrations and Ratios of Span 40/Tween 40 E
~. 8c Ratio of Span/Tween:
1 2 3 4 5 6 7 8 9 10 a
lOC ft.
Area of hysteresis loops (cm2) Emulsifier concentration (%, w / w )
120
3/7
4/6
6/4
0
0
0
0 0 3.8 4.1 5.2 8.3 10.1 13.9 15.6
0 1.5 3.7 4.4 5.3 8.2 9.9 13.6 13.9
0 10.3 14.3 15.8 a 20.14 32.1 a 41.2 a 48.04 48.6 a
7/3
"~ 6C
0 0 10.3 14.1 15.9 a 23.1 a 32.44 38.1 ~ 40.7 ~ 43.5 a
,~
4C
20
lO
o
2
4
Emulsifier
6
8
10
concentration (% w / w )
FIG. 3. Effectof concentration and ratio of Span/Tween on apparent viscositiesof emulsions (oil content 40%, w/ w). Span/Tween ratio 3/7 (11),Span/Tween ratio 4/6 (A), Span/Tween ratio 6/4 (O), Span/Tween ratio 7/3 (0).
Exhibited spurs in the up curves of their rheograms.
moduli and their respectively associated viscosities 7/1, ~/2; and a Newtonian viscosity nNAll other emulsions were characterized by four parameters only, viz., Eo, El, 01, tiN. In general the age of the emulsion did not affect the values of the different parameters significantly except ~N which decreased with age. Figures 4 and 5 typically show the effects of concentration of emulsifiers on the creep compliance J, and on
240[
2oo[
"¢,.
the various other viscoelastic parameters at two different oil concentrations. J, was found to decrease and the other parameters to increase asymptotically with emulsifier concentration. Electron micrographs of some representative viscoelastic emulsions, obtained from carbon replicas prepared by the freeze fracture technique, are shown in Figs. 6A and 6B. The droplets were flocculated and the layers of what can be interpreted as a liquid crystalline phase can be clearly observed. Figure 6C shows the droplets from an emulsion not exhibiting viscoelasticity; here there is no evidence of a layered structure, cf. Ref. (5).
160
DISCUSSION "~ 120
8o 40
o 1~
~"
"o
7'o
Oil contents {% w / w )
FIG. 2. Effectofoil contents on the apparent viscosities of emulsions containing 10% (w/w) emulsifier. Span/ Tween ratio, 3/7 (11), Span/Tween ratio 4/6 (A), Span/ Tween ratio 6/4 (O), Span/Tween ratio 7/3 (0). Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
On the basis of the viscosity results (Fig. 3) and of the data in Tables I and II, it seems reasonable to suggest that, depending upon the Span/Tween ratios used, an increase in the total concentration of emulsifiers causes structural rearrangements to take place in the systems. These could be responsible for the observed rheological properties. The total concentration of Span/Tween used was always substantially greater than that required to form a complete monomolecular
553
F O R M A T I O N OF LIQUID CRYSTALS IN EMULSIONS TABLE II
Viscoelastic Parameters of Emulsions Containing 10% (w]w) Span]Tween in a Ratio of 6/4 and Different Concentrations of Oil Age of emulsions (h)
Eo (N -j m 2 X 10-3)
0.5 6.0 24.0
21.25 19.62 19.62
30
0.5 6.0 24.0
40
50
Concentration ofoil (%, W/W)
20
E~ (N -~ m e X 10-3)
7/1 (P X 102)
rl (s)
E2 (N -~ m 2 X 10-a)
8.49 8.58 8.58
1.27 1.03 1.03
15 12 12
--
--
--
1.91 1.45 1.45
45.54 42.50 42.50
7.77 7.77 7.77
0.77 0.70 0.70
10 9 9
7.58 7.58 8.00
0.30 0.30 0.32
4.0 4.0 4.0
2.46 1.91 1.91
0.5 6.0 24.0
63.75 63.75 63.75
18.92 18.92 18.11
1.91 1.89 1.92
11 10 10
9.25 9.07 9.07
0.37 0.36 0.36
4.0 4.0 4.0
2.66 1.54 1.54
0.5 6.0 24.0
47.03 50.74 50.74
11.23 10.02 10.02
0.89 0.81 0.81
8 8 8
--
--
--
2.33 1.91 1.91
film around the droplets. After a monomolecular layer has formed, the surplus emulsifier molecules could associate to form micelles in the continuous phase. Some water is entrapped between the polar groups of the surfactants. This process increases the volume ratio of the dispersed phase to the "free" continuous phase and this explains the observed increase in viscosity with emulsifier concentration of the system containing up to 5% (w/w) emulsifier (23). Each excess molecule of emulsifier, for
~
lxlO~
1X10' J,(Nm-2)
/
~ Emulsifier
/ concentration
1-2 (s)
7IN (P X l0 S)
example, would immobilize 2.88 X 10 -24 ml of aqueous phase in a system containing 10% oil and 5% Span/Tween at a 3/7 ratio, and 1.86 X 10 _24 ml in a system containing 40% oil. When the bulk concentration of Span/ Tween in the ratios of 6/4 and 7/3 is further increased beyond 5% (w/w), a structural rearrangement takes place as proposed earlier. This changes the ordering of the micelles to form lyotropic liquid crystals both in the con-
250 5 X 10-2 200
% T"
z
>. 150 ~11p o i s e s
.2 m lx10
2
1 O0 ¢ w
lX105
72 (P X 102)
111 113 {% w / w )
50
150
FIG. 4. Variation of creep compliance parameter J~ (after 0.5 h) and nl (after 6 h) with emulsifier concentration in systems containing 40% (w/w) oil. Span/Tween ratio 6/4 (e), Span/Tween ratio 7/3 (0).
! 1 × 1 0 -E
I 7 Emulsifier
I 9
I 11
concentration
I 13 {% w / w )
I 15
FIG. 5. Effect of concentration of emulsifiers on the instantaneous elasticity (Eo) of emulsions containing 30% (w/w) oil (after 6 h). Span/Tween ratio 6/4 (e), Span/ Tween ratio 7/3 (0). Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
554
PILPEL AND RABBANI
FIG. 6A-C. Some representative electron photomicrographs of emulsions containing 40% (w/w) oil and 10% (w/w) emulsifier in various ratios. (A) Span/Tween ratio 6/4; (B) Span/Tween ratio 7/3; (C) Span/ Tween ratio 3/7. Journal of Colloid and Interface Science, Vol. 119,No. 2, October1987
FORMATION OF LIQUID CRYSTALS IN EMULSIONS
555
FIG. 6--Continued.
tinuous phase and at the oil/water interface. The liquid crystals in a continuous phase form a network in which oil droplets are fixed (6). It is this network which is primarily responsible for the viscoelastic behavior exhibited by these emulsion systems. The strength of this network increases as the total emulsifier concentration is increased. This is indicated in the creep tests by falling compliances and rising elasticities and viscosities (Figs. 4 and 5) and in continuous shear tests by increasing loop area, Table I (24). Indirect evidence for the existence of liquid crystals in these viscoelastic emulsions is provided by a mathematical model due to Oldroyd (10, 11). His equation for their retardation time rl is r(16r/w+ 19r/o)[3 + r , = 40--6~w+--rto~ ] r/w 270
-~
(16~w+ 19~o)q5+ (~/o+ ~b)2]. 5(nw+7o)
[1]
He assumed that spherical droplets of oil of radius r, volume fraction ~b, viscosity 70, surrounded by a structurally ordered interracial film (i.e., liquid crystals), are dispersed in an aqueous phase of viscosity ~w. The interfacial tension across the film is denoted as Yu. In the present systems, r ~ 1 × 10- 6 m, q~ 0.4, ~/o ~ 100 cp, ~w ~ 1 cp, and rl is of the order of 10 s (Table II). Substituting these values in Eq. [1] leads to the conclusion that the value of % is very low, certainly less than 1 m N m 1. There is now circumstantial evidence to support the idea of such a low interfacial tension at the oil/water interface in stable viscoelastic emulsion systems (9, 25, 26). The indirect evidence for the ordered interfacial film is supported by the direct evidence of the electron microscopy which clearly indicates the presence of lamellar liquid crystals in the form of a layered structure around the droplets in Figs. 6A and 6B but not in Fig. 6C. Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
556
PILPEL AND
An attempt is now made to deduce a possible mechanism, on the basis of certain theoretical concepts, for the formation of the lamellar phase as the emulsifier concentration is increased. Lyotropic liquid crystals consist of ordered micelles and are formed by the interaction between the micelles (27). Different types of micelles give rise to different types of liquid crystals depending upon the circumstances. Therefore it should be possible to extend the theories of micelle shape to account for the mesophase formation by including appropriate terms for intermicellar forces. A number of theories to describe micelle shapes have been published (12-14). These involve a balance of alkyl chain/water repulsions and repulsion between adjacent head groups within the micelles together with surface curvature and limitation due to amphiphilic geometry. These geometric limitations impose restrictions on the allowed shapes of micelles and force some of the amphiphiles to assemble into those shapes which appear to be thermodynamically unfavorable. To investigate the possible shape of micelles and hence the type of liquid crystal present in the system, a model proposed by Israelachvili et al. (12) is employed. The underlying concept of this model is that the ratio of amphiphile hydrocarbon chain volume, v, to the length Ic, and the cross-sectional area near the head group, a0, decides the most likely shape of the micelles just above the CMC. At this low concentration of emulsifiers (amphiphiles) interactions between micelles have little or no influence on micelle shape. If V/aol~ < 0.33, a spherical micelle will form preferentially over cylindrical ones because of entropic reasons. With v/ao lo ~ 0.5 rod or cylindrical micelles can form. If0.5 < V/aol¢ < 1 rods are excluded and only bilayer micelles can form. To determine the packing ratio the values of v, Ic, and ao can be obtained from the equations v = (2.74 + 26.9n)~3 per hydrocarbon chain
[21 Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
RABBANI
lc = (1.5 + 1.265n) A per hydrocarbon chain
[3] 27reZD0 ao - - per amphiphile,
[4]
e'YE
where n is the number of carbons in the hydrocarbon chain, Do is the separation of the capacitor planes with charge e per unit area and dielectric constant e. (The capacitor represents the electrostatic repulsive energy of amphiphiles when they come close together). A repulsive energy of this form arises from a double layer of charge as in a capacitor and 3'E is the interfacial free energy arising from attractive hydrophobic or surface tension forces. For the purpose of calculation Do is taken as 0.4 nm, e = 40 (dielectric constant near the oil/water interface), 3'E as 50 m N m -1, and e as 4.08 × 10 -l° e.s.u. (12). From Eqs. [2]-[4] the values for v, lc, and ao were calculated and found to be 0.41 n m 3, 2.0 nm, and 0.61 nm 2, respectively. From these values, the packing ratio, v/aolo, comes out to be 0.34. It is appreciated that there might be a possibility of an error of_+5% in this figure because of the uncertainty of the values used in Eqs. [2]-[4]. Nevertheless this ratio seems to indicate that the amphiphiles can no longer pack into spheres but form cylindrical rod-shaped micelles. This inference is in agreement with that of Tanford (13, 28) that the amphiphiles with one hydrocarbon chain (as in the present case) invariably form rod-like micelles. In addition to other factors, the packing ratio is affected by the concentration of the amphiphiles in the system. The increase in the concentration would cause the rods to grow in size because the repulsion between the head groups decreases, i.e., a0 decreases and v/ao Ic increases. This effect is similar to that of the addition of sodium chloride to the micellar solution of sodium dodecyl sulfate (29). With a further increase in the amount of emulsifier, the volume fraction of micelles increases. The micelles are pushed close together to accommodate additional micelles and intermicellar forces begin to operate. These
FORMATION OF LIQUID CRYSTALS IN EMULSIONS
forces include, in addition to van der Waals' forces of attraction, a short-range, solventtransmitted, hydration repulsion accompanied by another repulsive force due to limitations on the conformation of ethylene oxide groups of Tween molecules arising from steric hindrance (30). This intermicellar repulsion is considered to be of the soft-core type; i.e., it occurs at a range of distances from the micelle surfaces. One possible consequence of softcore repulsion is an increase in the value of v~ a0 lc by further decreasing the value of a0 (unless ao is restricted by alkyl chain packing). This leads to a further increase in micelle size. If the v/ao lc value rises above the critical values given in the text, the micelles change shape in the sequence spheres ~ rods --~ bilayers. If the repulsion between the new shapes is sufficiently large, then an ordered phase can form immediately. Thus one might expect, at a particular concentration of emulsifiers, the intermicellar repulsion to become sufficiently large to transform rod micelles into a lamellar mesophase through the following phase sequences (the numbers refer to volume fractions of the micelles required for the phase transition) (31): 0.7
rod micelles--~ 0.91
hexagonal phase ~ lamellar phase.
557
crease the size of the micelles. Decreasing the intermicellar distances may increase the (repulsive) interaction energy. At some particular concentration of oil (probably 20% (w/w)) repulsive forces become sufficiently large to form the lamellar phase. Once a lamellar phase has formed in a system, then one might expect an increase in the size with a further increase in oil content. Such large structures would be expected to interact strongly and form a separate phase which does not appear to form a viscoelastic network. This explains why liquid crystals did not form in systems containing more than 50% (w/w) oil (14). The effect of Span/Tween ratios on V/aolc is difficult to predict without a better understanding of the forces at play. However, the formation ofa mesophase at a particular ratio of Span/Tween can be attributed to the hydrophilic portions of the two emulsifiers since their hydrophobic portions are identical. CONCLUSION
The rheological properties of sunflower oil in water emulsions were affected not only by the total concentration of Span 40/Tween 40 but also by the ratios in which these had been mixed. Emulsions containing Span/Tween in 6/4 and 7/3 ratios (>~5% (w/w)) and 20-50% (w/w) oil exhibited viscoelasticity and this was ascribed to the formation of a liquid crystalline phase both in the continuous medium and at the surface of the oil droplets. From the known values of the volumes, lengths, and cross-sectional areas of the emulsifier molecules and their resulting ability to pack into organized structures, coupled with the electron microscopic data, it is concluded that the liquid crystals are of lamella type.
The discussion to date encourages one to apply the theoretical concepts underlying the already discussed transition mechanisms in an attempt to explain the changes that occurred in the system with changes in oil content, i.e., the formation of lamellar mesophase between 20 and 50% (w/w) oil. For a fixed volume fraction of micelles the distances between them can be decreased by increasing the oil content (27). This reduces the water content and ACKNOWLEDGMENTS therefore increases the concentration of the water-soluble surfactant in the water. An alAdapted in part from M.E.R.'s Ph.D. thesis (University ternative explanation would be that more of of London, 1986). M.E.R. is grateful to the Ministry of the hydrophobic surfactant dissolves in the oil, Education, Government of Pakistan for the award of a Central Overseas Training Scholarship and to Bahauddin thus changing the emulsifier ratio. There is a Zakariya University, Multan, Pakistan for granting study decrease in ao which, through the packing leave. We thank Dr. A. P. R. Brain for providing the elecconditions, can either change the shape or in- tron photomicrographs.
Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
558
PILPEL AND RABBANI REFERENCES
1. Friberg, S., Mandell, L., and Larsson, M., J. Colloid Interface Sci. 29, 155 (1969). 2. Friberg, S., and Mandell, L. J., Pharm. Sci. 59, 1001 (t970). 3. Friberg, S., J. ColloM Interface Sci. 37, 291 (1971). 4. Friberg, S., Jansson, P. O., and Cederberg, E., J. Colloid Interface Sci. 55, 614 (1976). 5. Friberg, S. J., Soc. Cosmet. Chem. 30, 309 (1979). 6. Suzuki, T., Tsutsumi, H., and Ishida, A., J. Dispersion Sci. Technol. 5, 119 (t984). 7. Patel, H. K., Rowe, R. C., Mc Mahon, J., and Stewart, R. F., Int. J. Pharm. 25, 13 (1985). 8. Eccleston, G. M., J. Colloid Interface Sci. 57, 66 (1976). 9. Eshuis, A., and Mellema, J., Colloids Polym. Sci. 262, 159 (1984). 10. Oldroyd, J. G., Proc. R. Soc. London Ser. A. 218, 122 (1953). 11. Oldroyd, J. G., Proc. R. Soc. London Ser. A. 232, 567 (1955). 12. Israelachvili, J. N., Mitchell, D. J., and Ninham, B. W., J. Chem. Soc. Faraday Trans. 2 72, 1525 (1976). 13. Tanford, C,, "Hydrophobic Effects." Wiley, New York, 1980. 14. Mitchell, D. J., and Ninham, B. W., J. Chem. Soc. Faraday Trans. 2 77, 601 (1981). 15. Davis, S. S., Deer, J. J., and Warburton, B., J. Sci. Instrum. 1, Ser. 2, 933 (1968).
JournalofColloidandInterfaceScience.Vol.119,No. 2, October1987
16. Barry, B. W., and Grace, A. J., J. Pharm. Pharmacol. 22, 147S (1970). 17. Barry, B. W., in "Advances in Pharmaceutical Sciences" (H. S. Bean, A. H. Beckett, and J. E. Carless, Eds.), Vol. 4, p. 1. Academic Press, London, 1974. 18. Menold, R., Luttge, B., and Kaiser, W., Adv. Colloid Interface Sci. 5, 281 (t 976). 19. Stewart, R. F., and Sutton, D., Chem. Ind. 10, 373 (1984). 20. Inokuchi, K., Bull. Chem. Soc. Japan 28, 453 (I 955). 21. Warburton, B., and Barry, B. W., J. Pharm. Pharmacol. 20, 255 (1968). 22. Sherman, P., "Industrial Rheology." Academic Press, London, 1970. 23. Sherman, P., in "Emulsion Science" (P. Sherman, Ed.), p. 217. Academic Press, London, 1968. 24. Barry, B. W.,Adv. ColloidlnterfaceSci. 5, 37 (1975). 25. Ruckenstein, E., Soc. Pet. Eng. J. 21, 593 (1981). 26. Lee, G. W. J., and Tadros, Th.F., Colloids Surf. 5, 105 (1982). 27. Tiddy, G. J. T., Phys. Rep. 57, 1 (1980). 28. Tanford, C. J., Phys. Chem. 76, 3020 (1972). 29. Wennerstr6m, H., and Lindman, B., Phys. Rep. 52, 1 (1972). 30. Le Neveu, M., Rand, R. P., Parsegian, V. A., and Gingell, D., Biophys. J. 18, 209 (1977). 31. Mitchell, D. J., Tiddy, G. J. T., Waring, L., Bostock, T., and Mc Donald, M. P., J. Chem. Soc. Faraday Trans. 1 79, 975 (1983).
Received October 9, 1986; accepted December 9, 1986 Sunflower oil in water emulsions containing between 10-70% (w/w) oil and 1-15% (w/w) sorbitan monopalmitate (Span 40) and polyoxyethylene(20) sorbitan monopalmitate (Tween 40) in different ratios were prepared. Their rheological behavior was investigated by continuous shear rheometry and by creep viscometry.Emulsions containing >-5%(w/w) of Span/Tween in weight ratios of 6/4 and 7/3 exhibited viscoelasticity.This was ascribed to the presence of a lamellar type of liquid crystalline phase in the systemswhich was confirmed by electron microscopy. © 1987AcademicPress,Inc. INTRODUCTION
also presented which support the theory of stabilization of emulsions by a liquid crystalline phase. Knowing the molecular dimensions of the two emulsifiers employed it should, in principle, be possible to decide whether the liquid crystalline phase is of hexagonal, reversed hexagonal, or lamellar type (12-14).
The stability of viscoelastic emulsions prepared by using a mixture of a lipophilic and a hydrophilic emulsifier (such as Span and Tween) in high concentrations has been attributed to the formation of three-dimensional association structures of liquid crystals by Friberg and co-workers (1-5). Direct evidence for EXPERIMENTAL their presence and location has been obtained by optical and electron microscopic techMaterials. The oil used was an edible grade niques (4-7). Rheological measurements m a y also pro- of refined dewaxed sunflower seed oil (Alembic vide some indirect information about the Products, n 2° 1.475; d42° 0.9334; viscosity 100 cp at 20°C). The emulsifiers were samples of structure of the systems (8, 9). In the present work oil in water emulsions Span 40 (sorbitan monopalmitate) and Tween containing Span 40/Tween 40 in different ra- 40 (polyoxyethylene (20) sorbitan monopaltios and covering a wide range of concentra- mitate), supplied ~98.5% pure by Atlas tions were investigated by employing both a Chemicals. The water was distilled from an continuous shear rheometer and a variable all-glass still (surface tension 72.0 + 0.2 m N stress rheometer (in creep tests). Viscoelastic m -~ at 20°C, specific conductivity at 20°C, parameters were calculated and used to derive 1.4 × 10 -6 o h m -1 cm-1; p H 5.8 _+ 0.1). Methods. Oil in water emulsions were prethe structure of the systems on the basis of a pared containing 10-70% (w/w) oil and l-15% mathematical model for the viscoelastic (w/w) total emulsifier with the ratios of Span/ emulsions developed by Oldroyd (10, 11). Tween between 1/9 and 9/1 (w/w). The comSome new electron microscopic data are ponents were weighed out, heated to 45°C mixed with a mechanical stirrer for 5 min, and then cooled slowly and stored at 20°C in glass1To whom correspondence should be addressed. 2 Present address: Department of Pharmacy, Bahauddin stoppered bottles. Droplet sizes were measured Zakariya University, Multan, Pakistan. on a Coulter Model TA 11 counter (Coulter 550 0021-9797/87 $3.00 Copyright © 1987 by Academic Press, Inc. All rights of reproduction in any form reserved.
Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
FORMATION OF LIQUID CRYSTALS IN EMULSIONS Electronics) and expressed as mean volume surface diameters. Rheological examination. Samples were subjected to continuous shear at 20°C in a Ferranti-Shirley cone and plate viscometer using a 70-mm-diameter cone, a 1200 g cm torque spring, and an automatic gap setting device with a clearance of 2.5 ~m. The instrum e n t was operated at a m a x i m u m of 50 r p m and a sweep time of 60 s producing a maxim u m shear rate of 832 s-1. Rheograms of three replicates were plotted automatically and the areas of the hysteresis loops were determined with a planimeter, the scale expansion being dependent on the sample. Samples which exhibited spurs on the ascending curves of their rheograms were subjected to creep tests. The creep compliance behavior for the first 24 h after preparation was measured at 20°C with a concentric cylinder air turbine viscometer as discussed more fully elsewhere (15-17), and the data were analyzed graphically. Electron microscopy. Selected samples were frozen in slushed nitrogen at - 2 1 0 ° C and fractured at - 1 3 5 ° C under a v a c u u m of 1 N 10 -6 T o r t using a Polaron E7500 freeze fracture unit. Replicates were obtained by shadowing first with a platinum/carbon mixture at 45°C and then with carbon at 90 ° and were used to obtain electron micrographs at various magnifications with a Philips EM301G transmission electron microscope. For details of the technique, see Refs. (18, 19). RESULTS Figure 1 shows typical droplet size distribution plots of the freshly prepared emulsions. The m e a n droplet size depended on the concentration of oil and emulsifier and on the ratios of Span/Tween. It was m i n i m u m when the total emulsifier concentration was 10% (w/ w) and the ratio of Span/Tween was 6/4. Emulsions with >/5% (w/w) emulsifier exhibited non-Newtonian pseudo-plastic flow with hysteresis. The areas of the hysteresis loops increased with the increasing concentration of emulsifier, Table I, and were also af-
551
30
25
2O
o~
< 6
7
Droplet diameter (IJm)
FIG. 1. Droplet sizedistribution of emulsions containing 40% (w/w) oil and 10% (w/w) emulsifier. Span/Tween ratios, 3/7 (It), Span/Tweenratios4/6 (A), Span/Tweenratios 6/4 (O), Span/Tween ratios 7/3 (0).
fected by the concentration of oil and by the ratio of Span/Tween reaching a m a x i m u m at a ratio of 6/4 (w/w). Spurs occurred on the up curves of the rheograms in systems containing 20-50°70 (w/w) oil and >~5% (w/w) Span/Tween in the ratios of 6/4 and 7/3 only. The apparent viscosities (napp) of the samples at the m a x i m u m shear rate of 50 × 16.63 s-l, i.e., the viscosities of the Newtonian fluids which would show the same shear stress at this rate, are plotted typically against oil contents in Fig. 2, and against the total emulsifier contents and ratio in Fig. 3. napp increased with oil content and with total concentration of Span/Tween in any ratio but this increase became steeper with 5% (w/w) Span/Tween present in the 6/4 and 7/3 (w/w) ratios. The systems giving spurs in their rheograms exhibited viscoelasticity under the test conditions imposed. The viscoelastic parameters of the emulsions were derived from analysis of the creep curves by graphical methods (2022). Table II, typically summarizes the parameters derived from these curves. It is seen that the creep behaviors of the emulsions containing 30-40% (w/w) oil were characterized by six parameters. These are Eo, an instantaneous elastic modulus; El, E2, retarded elastic Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
552
PILPEL AND RABBANI TABLEI
Areas of the HysteresisLoops of Emulsions Containing 40% (w/w) Oil and Various Concentrations and Ratios of Span 40/Tween 40 E
~. 8c Ratio of Span/Tween:
1 2 3 4 5 6 7 8 9 10 a
lOC ft.
Area of hysteresis loops (cm2) Emulsifier concentration (%, w / w )
120
3/7
4/6
6/4
0
0
0
0 0 3.8 4.1 5.2 8.3 10.1 13.9 15.6
0 1.5 3.7 4.4 5.3 8.2 9.9 13.6 13.9
0 10.3 14.3 15.8 a 20.14 32.1 a 41.2 a 48.04 48.6 a
7/3
"~ 6C
0 0 10.3 14.1 15.9 a 23.1 a 32.44 38.1 ~ 40.7 ~ 43.5 a
,~
4C
20
lO
o
2
4
Emulsifier
6
8
10
concentration (% w / w )
FIG. 3. Effectof concentration and ratio of Span/Tween on apparent viscositiesof emulsions (oil content 40%, w/ w). Span/Tween ratio 3/7 (11),Span/Tween ratio 4/6 (A), Span/Tween ratio 6/4 (O), Span/Tween ratio 7/3 (0).
Exhibited spurs in the up curves of their rheograms.
moduli and their respectively associated viscosities 7/1, ~/2; and a Newtonian viscosity nNAll other emulsions were characterized by four parameters only, viz., Eo, El, 01, tiN. In general the age of the emulsion did not affect the values of the different parameters significantly except ~N which decreased with age. Figures 4 and 5 typically show the effects of concentration of emulsifiers on the creep compliance J, and on
240[
2oo[
"¢,.
the various other viscoelastic parameters at two different oil concentrations. J, was found to decrease and the other parameters to increase asymptotically with emulsifier concentration. Electron micrographs of some representative viscoelastic emulsions, obtained from carbon replicas prepared by the freeze fracture technique, are shown in Figs. 6A and 6B. The droplets were flocculated and the layers of what can be interpreted as a liquid crystalline phase can be clearly observed. Figure 6C shows the droplets from an emulsion not exhibiting viscoelasticity; here there is no evidence of a layered structure, cf. Ref. (5).
160
DISCUSSION "~ 120
8o 40
o 1~
~"
"o
7'o
Oil contents {% w / w )
FIG. 2. Effectofoil contents on the apparent viscosities of emulsions containing 10% (w/w) emulsifier. Span/ Tween ratio, 3/7 (11), Span/Tween ratio 4/6 (A), Span/ Tween ratio 6/4 (O), Span/Tween ratio 7/3 (0). Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
On the basis of the viscosity results (Fig. 3) and of the data in Tables I and II, it seems reasonable to suggest that, depending upon the Span/Tween ratios used, an increase in the total concentration of emulsifiers causes structural rearrangements to take place in the systems. These could be responsible for the observed rheological properties. The total concentration of Span/Tween used was always substantially greater than that required to form a complete monomolecular
553
F O R M A T I O N OF LIQUID CRYSTALS IN EMULSIONS TABLE II
Viscoelastic Parameters of Emulsions Containing 10% (w]w) Span]Tween in a Ratio of 6/4 and Different Concentrations of Oil Age of emulsions (h)
Eo (N -j m 2 X 10-3)
0.5 6.0 24.0
21.25 19.62 19.62
30
0.5 6.0 24.0
40
50
Concentration ofoil (%, W/W)
20
E~ (N -~ m e X 10-3)
7/1 (P X 102)
rl (s)
E2 (N -~ m 2 X 10-a)
8.49 8.58 8.58
1.27 1.03 1.03
15 12 12
--
--
--
1.91 1.45 1.45
45.54 42.50 42.50
7.77 7.77 7.77
0.77 0.70 0.70
10 9 9
7.58 7.58 8.00
0.30 0.30 0.32
4.0 4.0 4.0
2.46 1.91 1.91
0.5 6.0 24.0
63.75 63.75 63.75
18.92 18.92 18.11
1.91 1.89 1.92
11 10 10
9.25 9.07 9.07
0.37 0.36 0.36
4.0 4.0 4.0
2.66 1.54 1.54
0.5 6.0 24.0
47.03 50.74 50.74
11.23 10.02 10.02
0.89 0.81 0.81
8 8 8
--
--
--
2.33 1.91 1.91
film around the droplets. After a monomolecular layer has formed, the surplus emulsifier molecules could associate to form micelles in the continuous phase. Some water is entrapped between the polar groups of the surfactants. This process increases the volume ratio of the dispersed phase to the "free" continuous phase and this explains the observed increase in viscosity with emulsifier concentration of the system containing up to 5% (w/w) emulsifier (23). Each excess molecule of emulsifier, for
~
lxlO~
1X10' J,(Nm-2)
/
~ Emulsifier
/ concentration
1-2 (s)
7IN (P X l0 S)
example, would immobilize 2.88 X 10 -24 ml of aqueous phase in a system containing 10% oil and 5% Span/Tween at a 3/7 ratio, and 1.86 X 10 _24 ml in a system containing 40% oil. When the bulk concentration of Span/ Tween in the ratios of 6/4 and 7/3 is further increased beyond 5% (w/w), a structural rearrangement takes place as proposed earlier. This changes the ordering of the micelles to form lyotropic liquid crystals both in the con-
250 5 X 10-2 200
% T"
z
>. 150 ~11p o i s e s
.2 m lx10
2
1 O0 ¢ w
lX105
72 (P X 102)
111 113 {% w / w )
50
150
FIG. 4. Variation of creep compliance parameter J~ (after 0.5 h) and nl (after 6 h) with emulsifier concentration in systems containing 40% (w/w) oil. Span/Tween ratio 6/4 (e), Span/Tween ratio 7/3 (0).
! 1 × 1 0 -E
I 7 Emulsifier
I 9
I 11
concentration
I 13 {% w / w )
I 15
FIG. 5. Effect of concentration of emulsifiers on the instantaneous elasticity (Eo) of emulsions containing 30% (w/w) oil (after 6 h). Span/Tween ratio 6/4 (e), Span/ Tween ratio 7/3 (0). Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
554
PILPEL AND RABBANI
FIG. 6A-C. Some representative electron photomicrographs of emulsions containing 40% (w/w) oil and 10% (w/w) emulsifier in various ratios. (A) Span/Tween ratio 6/4; (B) Span/Tween ratio 7/3; (C) Span/ Tween ratio 3/7. Journal of Colloid and Interface Science, Vol. 119,No. 2, October1987
FORMATION OF LIQUID CRYSTALS IN EMULSIONS
555
FIG. 6--Continued.
tinuous phase and at the oil/water interface. The liquid crystals in a continuous phase form a network in which oil droplets are fixed (6). It is this network which is primarily responsible for the viscoelastic behavior exhibited by these emulsion systems. The strength of this network increases as the total emulsifier concentration is increased. This is indicated in the creep tests by falling compliances and rising elasticities and viscosities (Figs. 4 and 5) and in continuous shear tests by increasing loop area, Table I (24). Indirect evidence for the existence of liquid crystals in these viscoelastic emulsions is provided by a mathematical model due to Oldroyd (10, 11). His equation for their retardation time rl is r(16r/w+ 19r/o)[3 + r , = 40--6~w+--rto~ ] r/w 270
-~
(16~w+ 19~o)q5+ (~/o+ ~b)2]. 5(nw+7o)
[1]
He assumed that spherical droplets of oil of radius r, volume fraction ~b, viscosity 70, surrounded by a structurally ordered interracial film (i.e., liquid crystals), are dispersed in an aqueous phase of viscosity ~w. The interfacial tension across the film is denoted as Yu. In the present systems, r ~ 1 × 10- 6 m, q~ 0.4, ~/o ~ 100 cp, ~w ~ 1 cp, and rl is of the order of 10 s (Table II). Substituting these values in Eq. [1] leads to the conclusion that the value of % is very low, certainly less than 1 m N m 1. There is now circumstantial evidence to support the idea of such a low interfacial tension at the oil/water interface in stable viscoelastic emulsion systems (9, 25, 26). The indirect evidence for the ordered interfacial film is supported by the direct evidence of the electron microscopy which clearly indicates the presence of lamellar liquid crystals in the form of a layered structure around the droplets in Figs. 6A and 6B but not in Fig. 6C. Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
556
PILPEL AND
An attempt is now made to deduce a possible mechanism, on the basis of certain theoretical concepts, for the formation of the lamellar phase as the emulsifier concentration is increased. Lyotropic liquid crystals consist of ordered micelles and are formed by the interaction between the micelles (27). Different types of micelles give rise to different types of liquid crystals depending upon the circumstances. Therefore it should be possible to extend the theories of micelle shape to account for the mesophase formation by including appropriate terms for intermicellar forces. A number of theories to describe micelle shapes have been published (12-14). These involve a balance of alkyl chain/water repulsions and repulsion between adjacent head groups within the micelles together with surface curvature and limitation due to amphiphilic geometry. These geometric limitations impose restrictions on the allowed shapes of micelles and force some of the amphiphiles to assemble into those shapes which appear to be thermodynamically unfavorable. To investigate the possible shape of micelles and hence the type of liquid crystal present in the system, a model proposed by Israelachvili et al. (12) is employed. The underlying concept of this model is that the ratio of amphiphile hydrocarbon chain volume, v, to the length Ic, and the cross-sectional area near the head group, a0, decides the most likely shape of the micelles just above the CMC. At this low concentration of emulsifiers (amphiphiles) interactions between micelles have little or no influence on micelle shape. If V/aol~ < 0.33, a spherical micelle will form preferentially over cylindrical ones because of entropic reasons. With v/ao lo ~ 0.5 rod or cylindrical micelles can form. If0.5 < V/aol¢ < 1 rods are excluded and only bilayer micelles can form. To determine the packing ratio the values of v, Ic, and ao can be obtained from the equations v = (2.74 + 26.9n)~3 per hydrocarbon chain
[21 Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
RABBANI
lc = (1.5 + 1.265n) A per hydrocarbon chain
[3] 27reZD0 ao - - per amphiphile,
[4]
e'YE
where n is the number of carbons in the hydrocarbon chain, Do is the separation of the capacitor planes with charge e per unit area and dielectric constant e. (The capacitor represents the electrostatic repulsive energy of amphiphiles when they come close together). A repulsive energy of this form arises from a double layer of charge as in a capacitor and 3'E is the interfacial free energy arising from attractive hydrophobic or surface tension forces. For the purpose of calculation Do is taken as 0.4 nm, e = 40 (dielectric constant near the oil/water interface), 3'E as 50 m N m -1, and e as 4.08 × 10 -l° e.s.u. (12). From Eqs. [2]-[4] the values for v, lc, and ao were calculated and found to be 0.41 n m 3, 2.0 nm, and 0.61 nm 2, respectively. From these values, the packing ratio, v/aolo, comes out to be 0.34. It is appreciated that there might be a possibility of an error of_+5% in this figure because of the uncertainty of the values used in Eqs. [2]-[4]. Nevertheless this ratio seems to indicate that the amphiphiles can no longer pack into spheres but form cylindrical rod-shaped micelles. This inference is in agreement with that of Tanford (13, 28) that the amphiphiles with one hydrocarbon chain (as in the present case) invariably form rod-like micelles. In addition to other factors, the packing ratio is affected by the concentration of the amphiphiles in the system. The increase in the concentration would cause the rods to grow in size because the repulsion between the head groups decreases, i.e., a0 decreases and v/ao Ic increases. This effect is similar to that of the addition of sodium chloride to the micellar solution of sodium dodecyl sulfate (29). With a further increase in the amount of emulsifier, the volume fraction of micelles increases. The micelles are pushed close together to accommodate additional micelles and intermicellar forces begin to operate. These
FORMATION OF LIQUID CRYSTALS IN EMULSIONS
forces include, in addition to van der Waals' forces of attraction, a short-range, solventtransmitted, hydration repulsion accompanied by another repulsive force due to limitations on the conformation of ethylene oxide groups of Tween molecules arising from steric hindrance (30). This intermicellar repulsion is considered to be of the soft-core type; i.e., it occurs at a range of distances from the micelle surfaces. One possible consequence of softcore repulsion is an increase in the value of v~ a0 lc by further decreasing the value of a0 (unless ao is restricted by alkyl chain packing). This leads to a further increase in micelle size. If the v/ao lc value rises above the critical values given in the text, the micelles change shape in the sequence spheres ~ rods --~ bilayers. If the repulsion between the new shapes is sufficiently large, then an ordered phase can form immediately. Thus one might expect, at a particular concentration of emulsifiers, the intermicellar repulsion to become sufficiently large to transform rod micelles into a lamellar mesophase through the following phase sequences (the numbers refer to volume fractions of the micelles required for the phase transition) (31): 0.7
rod micelles--~ 0.91
hexagonal phase ~ lamellar phase.
557
crease the size of the micelles. Decreasing the intermicellar distances may increase the (repulsive) interaction energy. At some particular concentration of oil (probably 20% (w/w)) repulsive forces become sufficiently large to form the lamellar phase. Once a lamellar phase has formed in a system, then one might expect an increase in the size with a further increase in oil content. Such large structures would be expected to interact strongly and form a separate phase which does not appear to form a viscoelastic network. This explains why liquid crystals did not form in systems containing more than 50% (w/w) oil (14). The effect of Span/Tween ratios on V/aolc is difficult to predict without a better understanding of the forces at play. However, the formation ofa mesophase at a particular ratio of Span/Tween can be attributed to the hydrophilic portions of the two emulsifiers since their hydrophobic portions are identical. CONCLUSION
The rheological properties of sunflower oil in water emulsions were affected not only by the total concentration of Span 40/Tween 40 but also by the ratios in which these had been mixed. Emulsions containing Span/Tween in 6/4 and 7/3 ratios (>~5% (w/w)) and 20-50% (w/w) oil exhibited viscoelasticity and this was ascribed to the formation of a liquid crystalline phase both in the continuous medium and at the surface of the oil droplets. From the known values of the volumes, lengths, and cross-sectional areas of the emulsifier molecules and their resulting ability to pack into organized structures, coupled with the electron microscopic data, it is concluded that the liquid crystals are of lamella type.
The discussion to date encourages one to apply the theoretical concepts underlying the already discussed transition mechanisms in an attempt to explain the changes that occurred in the system with changes in oil content, i.e., the formation of lamellar mesophase between 20 and 50% (w/w) oil. For a fixed volume fraction of micelles the distances between them can be decreased by increasing the oil content (27). This reduces the water content and ACKNOWLEDGMENTS therefore increases the concentration of the water-soluble surfactant in the water. An alAdapted in part from M.E.R.'s Ph.D. thesis (University ternative explanation would be that more of of London, 1986). M.E.R. is grateful to the Ministry of the hydrophobic surfactant dissolves in the oil, Education, Government of Pakistan for the award of a Central Overseas Training Scholarship and to Bahauddin thus changing the emulsifier ratio. There is a Zakariya University, Multan, Pakistan for granting study decrease in ao which, through the packing leave. We thank Dr. A. P. R. Brain for providing the elecconditions, can either change the shape or in- tron photomicrographs.
Journal of Colloid and Interface Science, Vol. 119, No. 2, October 1987
558
PILPEL AND RABBANI REFERENCES
1. Friberg, S., Mandell, L., and Larsson, M., J. Colloid Interface Sci. 29, 155 (1969). 2. Friberg, S., and Mandell, L. J., Pharm. Sci. 59, 1001 (t970). 3. Friberg, S., J. ColloM Interface Sci. 37, 291 (1971). 4. Friberg, S., Jansson, P. O., and Cederberg, E., J. Colloid Interface Sci. 55, 614 (1976). 5. Friberg, S. J., Soc. Cosmet. Chem. 30, 309 (1979). 6. Suzuki, T., Tsutsumi, H., and Ishida, A., J. Dispersion Sci. Technol. 5, 119 (t984). 7. Patel, H. K., Rowe, R. C., Mc Mahon, J., and Stewart, R. F., Int. J. Pharm. 25, 13 (1985). 8. Eccleston, G. M., J. Colloid Interface Sci. 57, 66 (1976). 9. Eshuis, A., and Mellema, J., Colloids Polym. Sci. 262, 159 (1984). 10. Oldroyd, J. G., Proc. R. Soc. London Ser. A. 218, 122 (1953). 11. Oldroyd, J. G., Proc. R. Soc. London Ser. A. 232, 567 (1955). 12. Israelachvili, J. N., Mitchell, D. J., and Ninham, B. W., J. Chem. Soc. Faraday Trans. 2 72, 1525 (1976). 13. Tanford, C,, "Hydrophobic Effects." Wiley, New York, 1980. 14. Mitchell, D. J., and Ninham, B. W., J. Chem. Soc. Faraday Trans. 2 77, 601 (1981). 15. Davis, S. S., Deer, J. J., and Warburton, B., J. Sci. Instrum. 1, Ser. 2, 933 (1968).
JournalofColloidandInterfaceScience.Vol.119,No. 2, October1987
16. Barry, B. W., and Grace, A. J., J. Pharm. Pharmacol. 22, 147S (1970). 17. Barry, B. W., in "Advances in Pharmaceutical Sciences" (H. S. Bean, A. H. Beckett, and J. E. Carless, Eds.), Vol. 4, p. 1. Academic Press, London, 1974. 18. Menold, R., Luttge, B., and Kaiser, W., Adv. Colloid Interface Sci. 5, 281 (t 976). 19. Stewart, R. F., and Sutton, D., Chem. Ind. 10, 373 (1984). 20. Inokuchi, K., Bull. Chem. Soc. Japan 28, 453 (I 955). 21. Warburton, B., and Barry, B. W., J. Pharm. Pharmacol. 20, 255 (1968). 22. Sherman, P., "Industrial Rheology." Academic Press, London, 1970. 23. Sherman, P., in "Emulsion Science" (P. Sherman, Ed.), p. 217. Academic Press, London, 1968. 24. Barry, B. W.,Adv. ColloidlnterfaceSci. 5, 37 (1975). 25. Ruckenstein, E., Soc. Pet. Eng. J. 21, 593 (1981). 26. Lee, G. W. J., and Tadros, Th.F., Colloids Surf. 5, 105 (1982). 27. Tiddy, G. J. T., Phys. Rep. 57, 1 (1980). 28. Tanford, C. J., Phys. Chem. 76, 3020 (1972). 29. Wennerstr6m, H., and Lindman, B., Phys. Rep. 52, 1 (1972). 30. Le Neveu, M., Rand, R. P., Parsegian, V. A., and Gingell, D., Biophys. J. 18, 209 (1977). 31. Mitchell, D. J., Tiddy, G. J. T., Waring, L., Bostock, T., and Mc Donald, M. P., J. Chem. Soc. Faraday Trans. 1 79, 975 (1983).