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The limiting solubilizing capacity of some nonionic surfactants
The Limiting Solubilizing Capacity of Some Nonionic Surfactants LUCY S. C. WAN Department o f Pharmacy, University o f Singapore, Singapore 0316 R e c e i v e d A u g u s t 15, 1979; a c c e p t e d F e b r u a r y 27, 1980
direct sunlight, it was found that there was a marked change in viscosity of the oil and that the exposed oil became "sticky," giving rise to a strong adhesion to surfaces of contact. A similar occurrence was observed in locations where the heating of corn oil was carried out over a period of time and the surrounding surfaces then became " s t i c k y " to the touch. They appeared to have become coated with a film of an adhesive substance. Ordinary washing with soap and water was not effective in removing the oil from such surfaces: abrasive action was required. Thus, it was thought that it would be interesting and perhaps useful to study the solubilization of corn oil. This report gives an account of the attempts to solubilize corn oil. Corn oil (Mazola, Best Foods Div., CPC International Inc., N. J.) of commercial grade was used. The nonionic surfactants used were polyoxyethylene sorbitan monolaurate, -monopalmitate, -monostearate, and -monooleate, which are water soluble, and sorbitan monolaurate, -monooleate, and -trioleate, which are oil dispersible (Honeywill-Atlas, London, England). A fixed quantity of corn oil or oily dispersion (0.01 g) containing corn oil and a sorbitan ester was added to a series of 25 ml of polysorbate solutions of increasing concentration, in graduated stoppered glass cylinders, which were allowed to rotate at 25 _+ 0.5°C in a water bath for about 6 h, The amounts of sorbitan ester added to the corn oil were such as to produce dispersions
Aqueous solutions of surfactants above the CMC have the ability to solubilize poorly water-soluble or -insoluble compounds. A literature survey shows that polysorbates (Tweens) have been used to solubilize a wide range of pharmaceutical substances including benzoic acid derivatives, essential oils, and fat-soluble vitamins (1). In addition, drugs such as sedatives, sulfonamides, analgesics, and antipyretics have also been solubilized in aqueous solutions of Tween 20 and 80 (1). Choulis (2) found that the solubilization of testosterones and amphetamines in aqueous Tween 20 and 40 solutions increased with increasing surfactant concentration above the CMC and no solubilization occurred below the CMC or when micelles were absent. In a study which involved compounds of varying polarity and nonionic surfactants, it was shown that the solubilities of the compounds studied, such as benzene, decane, and hydroxybenzoates in cetomacrogol solutions, were not adequately described solely on the basis of solubility into the separate regions of the micelle. Micellar solubility of the compounds was dependent on the hydrocarbon solubility and the presence of groups in the molecule which can form hydrogen bonds. The hydrophile-lipophile characteristics of the surface-active agent with the polarity of solubilizing molecule also affected solubilization (3). In the course of an investigation into the effect of corn oil in locations exposed to 401
Journal of Colloidand Interface Science, Vol. 78, No. 2, December 1980
0021-9797/80/120401-06502.00/0 Copyright © 1980 by Academic Press, Inc. All rights of reproduction in any form reserved.
402
LUCY
S. C. W A N
containing surfactant concentrations ranging from 5 to 40%. The presence or absence of oil droplets in the dispersion was examined under an illuminated light source. For reference, a control containing the same amount of oil as that in the test sample, but dispersed in water, was used. Solubilization of the oil or oily dispersion was considered to have occurred when the system contained a comparatively small number of oil droplets. Corn oil is highly insoluble and extremely hydrophobic. Aqueous solutions of polyoxyethylene sorbitan monooleate were used to solubilize the oil but without success. Other polysorbates, polyoxyethylene sorbitan monolaurate, -monopalmitate, and -monostearate, were also included in the study but these too were not able to solubilize the oil, despite the fact that the range of surfactant concentration used was very wide, from 0.01 to 10% (Table I). Hence a combination or mixture of surfactants was selected in an attempt to bring about solubilization. In a mixed surfactant system it is believed that solubilization is effected by the formation of mixed micelles. This has been demonstrated by evidence from cloud point determinations (4, 5) and from electrophoretic and specific conductivity measurements (6, 7). Gerbacia et al. (8) studied solubilization in an aqueous mixed micellar solution, the system being water-potassium oleate-pentanol-benzene, and found that
the major part of belizene solubilized in mixed micelles was in a relatively nonpolar environment. In a study of the binding of antihistamines to nonionic surfactants via mixed micelle formation, it was shown that mixed micelle formation was not influenced by changes in electrolyte concentration and pH, but was dependent on surfactant structure (9). In the present study, the mixed surfactants were from the sorbitan esters and polysorbates. Polyoxyethylene sorbitan esters had been used in the solubilization of simple hydrocarbons and essential oils, and the data obtained showed that the solubilizing capacities of these surfactants increased with decrease in the polyoxyethylene chain length of the homologous series (10, 11). The results obtained from this work showed that corn oil containing 5% sorbitan monooleate was not solubilized in solutions of polyoxyethylene sorbitan monooleate of varying concentrations (Table II), which were well above the CMC and therefore contained sufficient micelles to take up the oil; the CMC of polyoxyethylene sorbitan monooleate was 0.0014% as determined from surface tension measurements. It is known that solubilization can occur in one of several sites, such as inclusion into the hydrocarbon interior of the micelle or deep penetration into the palisade layer. It may also be either short penetration into the palisade layer or adsorption on t h e
TABLE
I
E x a m i n a t i o n o f A q u e o u s D i s p e r s i o n s o f P o l y s o r b a t e s t o W h i c h a F i x e d W e i g h t o f C o r n Oil w a s A d d e d , f o r t h e P r e s e n c e / A b s e n c e o f Oil D r o p l e t s a t 25°C Polysorbate concentration (%)
Polyoxyethylene sorbitan monooleate -sorbitan monostearate -sorbitan monopalmitate -sorbitan monolaurate ++,
0
0.01
0.02
0.1
0.6
1.0
2.0
5.0
9.0
10.0
++~ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
+ + + +
l a r g e n u m b e r o f oil d r o p l e t s ; + , s m a l l n u m b e r o f oil d r o p l e t s .
Journal of Colloid and Interface Science, Vol. 78, No. 2, December 1980
LIMITING
SO LUBILIZING
403
CAPACITY
TABLE II Examination of Aqueous Dispersions of Polyoxyethylene Sorbitan Monooleate to Which was Added a Fixed Quantity of Corn Oil Containing Varying Amounts of Sorbitan Monooleate for the Presence/Absence of Oil Droplets at 25°C Corn oil + sorbitan monooleate (%) ~ +5%
Polyoxyethylene sorbitan monooleate (%) 0
0.01
0.02
0.1
0.6
1.0
2.0
5.0
9.0
10.0
++a
++
++
++
++
++
++
++
++
+
+10%
++
++
++
++
++
++
++
++
++
+
+20%
++
++
++
++
++
++
++
++
++
+
+25%
++
++
++
++
++
++
++
++
++
+
+35%
++
++
++
++
++
++
++
++
++
+
+40%
++
++
++
++
++
++
++
++
++
+
a ++, large number of oil droplets; +, smallnumber of oil droplets. surface of micelles. For nonionic surfactants, possessing polyoxyethylene groups, it has been suggested that another mode of solubilization is possible, that is, the micelle is considered to be made up of two parts, one is the inner core of hydrocarbon tails, and the other is the outer shell of hydrated polyoxyethylene (12). None of these modes of solubilization seems to be applicable to the solubilization of corn oil. It should be noted also that the sites of solubilization are not fixed. There is a rapid equilibrium between various possible sites. In addition, there is an equilibrium between the solubilized state and the free state in the aqueous medium of solubilized species (13). The locus of solubilization has been investigated as can be seen in the study of solubilization of chlorpromazine in Tween 80 solutions. The findings indicate that the locus of solubilization is principally hydrophobic (14). In the solubilization of benzoic acid derivatives in nonionic surfactant solutions, Mukerjee (15) discussed the relative importance of the hydrophobic core of the micelle and the hydrophilic exterior as the seat of solubilizing action. The distribution of the solubilizate between the two loci was shown to be related to the chemical structure of the solubilizate. It is important to understand the physical and chemical reactivities of the solubilized species. Increasing the proportion of sorbitan
ester present in the corn oil from 5% to 10, 20, 25, 35, and 40% did not effect an appreciable amount of solubilization (Table II). Similar observations were noted for oil containing sorbitan monolaurate and also for that containing the trioleate ester under the same conditions. Aqueous solutions of the other polysorbates, that is, polyoxyethylene sorbitan monolaurate, -monopalmitate, and -monostearate, were also employed to solubilize the oil. But oil droplets in as large a number as that in the control were clearly visible in these dispersions. It would seem, therefore, that the mixed surfactants were not able to solubilize the oil. Micellar weight in aqueous solutions of polyoxyethylene-type nonionic surfactants increases and the CMC decreases with increase in temperature and this change in micellar weight in nonionic surfactant solutions containing a solubilizate has been studied by Nakagawa et al. (16). The greater the micellar weight, the greater is the number of solubilizate molecules per micelle and hence the amount solubilized increases with increasing temperature. Studies of solubilization of griseofulvin in nonionic surfactant solutions at temperatures ranging from 25 to 37.5°C showed that solubilization of the antibiotic increased with increasing temperature (17). However, in this study, increasing the temperature Journal of Colloid and Interface Science, Vol. 78, No. 2, December 1980
404
L U C Y S. C. W A N
from 25°C to 35, 45, 60, 80, and 90°C was of no effect on the solubilization of the oil. Just as in the control, a large number of oil droplets were found in all dispersions at these temperatures. Extending the period of rotation in the water bath from 4 to 6 hr and for a further period of up to 8 hr as well as applying more vigorous agitation to disperse the oily mixture in the aqueous solution by means of increasing the speed of rotation in the bath did not produce a significant reduction in the number of oil droplets in the system. All these factors which can assist solubilization have failed to solubilize corn oil. Similar experiments were carried out for corn oil exposed to sunlight and the results obtained were the same, in that exposed corn oil could not be solubilized by either solutions of polysorbates or by a combination of surfactants in the system. Since interaction between the surfactants in both phases is likely to occur at the interface, it was considered necessary to determine whether this interfacial activity would
exert any influence on the solubilization study. The surface or interfacial tension of various systems was measured using the Du Nouy tensiometer at 25°C (Cambridge Instrument Co., England) under standardized conditions of equilibration for aging effects. The oil and aqueous phases were allowed to come into contact for about 4 hr before measurement was begun. The ring was allowed to remain at the interface for a period of 30 min before being detached from the interface to make the measurement. This period of time was found to be suitable from preliminary experiments. Figure 1 shows the change in the interfacial tension between corn oil containing a fixed amount of sorbitan monooleate and solutions of pol yoxyet hyl ene sorbitan monooleate of varying concentrations. The pattern of behavior with respect to the lowering of the interfacial tension was not different from that seen with aqueous solutions of the same polysorbate (Fig. 2). A higher concentration of the oil-soluble surfactant produced a greater depression of
[-
Z Xc
~
"~4
X ~
x
_~.
x~
--4
~ - ~
X-------__
~x I
t
I 0.2
I
I 04
I I I I i I i l l I i l i 0.6 O.S I.(3 1.2 L4 1.6 -L Potyoxyethytene s,orbitan monooteate~ % X 10
i I.B'
FIG. h Effect of a fixed sorbitan monooleate (SM) concentration in corn oil on the interfacial tension between this oil and polyoxyethylene sorbitan monooleate solutions of varying concentrations at 25°C. SM concentration, %: (&) 0%; ((3) 0.001%; ( × ) 0.01%. Journal of Colloid and Interface Science, Vol. 78, No. 2, December 1980
LIMITING SOLUBILIZING CAPACITY
J ZE 4 c
~" " e -
-e ~
,,0-
-
o L -
--O-
405
-o-
¢ql
X3.~ to ffl c
•=~ A
A
A
&
,L
~-
~ 25
0
-x . . . . . . .
.
t q2
I 0.4
I 0.5
I O.n
I t.O
I 1.2
0
x_
I L,4
t!6
PoLyoxyeth¥lene sorbitan monooLeate or sorbitan monooLeate~/oX
I f.8 ,.~ 10
FIG. 2. Surface/interfacial tension curves for air/surfactant solution, air/corn oil, and corn oil/water systems in which surfactant is present or absent in one or both phases at 25°C. Dashed curves, polyoxyethylene sorbitan monooleate (PSM) in water; solid curves, sorbitan monooleate (SM) in oil; (O) PSM in water; (A) SM in corn oil; (©) SM in corn oil/water; (×) corn oil/PSM in water. the interfacial tension. Although the quantities of surfactant, both in the oil phase and in the aqueous phase, were m u c h less than those used in the solubilization study, nevertheless, the low interfacial tension attained in these s y s t e m s shows that solubilization of corn oil was not facilitated b y this condition existing at the interface. Similar results were obtained for corresponding systems in which either sorbitan monolaurate or the trioleate ester was added to the oil phase. It was o b s e r v e d that with high surfactant concentrations such as those used in the solubilization studies, there was a t e n d e n c y for spontaneous emulsification to
o c c u r at the interface, in which case the interfacial tension was reduced to such an extent that the ring was readily detached f r o m the interface. The surface tension o f corn oil containing varying a m o u n t s of sorbitan ester did not change with increasing concentration of the surfactant; there was no sharp b r e a k in the graph plotted as shown in Fig. 2, which is in contrast to that d e m o n s t r a t e d by aqueous solutions o f the c o r r e s p o n d i n g watersoluble surfactant. This indicates that there is no micellization. It is known, h o w e v e r , that micelles can be f o r m e d in n o n a q u e o u s solvents but these are mainly h y d r o c a r b o n s Journal of Collold and Interface Seience, VoI. 78, No. 2, December 1980
406
LUCY S. C. WAN
or solvents whose solvent properties are similar to those of the hydrocarbons (18). In the case of micelle formation in nonaqueous media, the solvophobic interactions of surfactants in nonaqueous media are weaker than those involving micelles in aqueous solutions. In solvents which are highly nonpolar, the polar groups of the surfactants become solvophobic and in such solvents, aggregates form in which the polar groups form the core. These are termed inverse, reverse, or reverted micelles. The aggregation properties of surfactants in nonaqueous media may be altered greatly by the presence of traces of water or other additives. The general problems of the different patterns of self-association and the need for cooperativity for the existence ofa CMC are the same for nonaqueous media as for aqueous media (19). It is not known whether micelles can be formed in oil. Data on the interfacial tension of liquid/liquid systems were also included in Fig. 2 for comparison with those of the air/liquid systems. It is seen that there is a marked depression of the interracial tension when the air phase is replaced by an oil phase. To summarize, the results of this investigation show that corn oil is not solubilized by either aqueous solutions of polyoxyethylene sorbitan esters or by a combination of these surfactants with sorbitan esters. Although the presence of a surfactant in the solubflizate lowers the interfacial tension between the solubilizate and the solubilizer, it is not able to bring about solubilization of a difficult solubilizate such as corn oil. The general statement that surfactants which form micelles are able to solubilize water-insoluble compounds is perhaps not as widely applicable as is commonly believed. The findings suggest that
Journal of Colloidand Interface Science, Vol. 78, No. 2, December1980
nonionic surfactants of the polyoxyethylene sorbitan ester type as well as the sorbitan esters have limiting capacities to solubilize extremely hydrophobic substances such as corn oil. REFERENCES 1. Sj6blom, L., "Solvent Properties of Surfactant Solutions" (K. Shinoda, Ed.), p. 189. Arnold, London, 1967. 2. Choulis, N. H., Pharmazie 28, 376 (1973). 3. Corby, T. C., and Elworthy, P. H., J. Pharm. Pharmacol. 23, 395 (1971). 4. Maclay, W. N., J. Colloid Sci. 11,272 (1956). 5. Kuriyama, K., Inoue, H., and Nakagawa, T., Kolloid Z. 183, 68 (1962). 6. Nakagawa, T., and Inoue, H., Nippon Kagaku Zasshi 78, 636 (1957). 7. Tokiwa, F., and Moriyama, N., J. Colloid Interface Sci. 30, 338 (1969). 8. Gerbacia, W. E., Rosano, H. L., and Zajac, M., J. Amer. Oil Chem. Soc. 53, 101 (1976). 9. Thoma, K., and Siemen, E., Pharm. Ind. 38, 193 (1976). 10. Sj6blom, L., "Solvent Properties of Surfactant Solutions" (K. Shinoda, Ed.), p. 200. Arnold, London, 1967. 11. Gluzman, R. G., and Lyashenko, S. S., Farmatsiya (Moscow) 17, 11 (1968). 12. Nagakawa, T., "Nonionic Suffactants" (M. J. Schick, Ed.), p. 558. Arnold, London, 1967. 13. Mittal, K. L., "Micellization, Solubilization and Microemulsions," p. 11. Plenum, New York, 1977. 14. Nguyen, D. P., and Paiement, J., Canad. J. Pharm. Sci. 7, 117 (1972). 15. Mukerjee, P., J. Pharm. Sci. 60, 1528 (1971). 16. Nakagawa, T., Kuriyama, K., and Inoue, H., in "12th Symposium on Colloid Chemistry," p. 32. Chem. Soc. Japan, 1959. 17. Kassem, A. A., and Mursi, N. M., Bull. Fac. Pharm. Cairo Univ. 9, 11 (1970). 18. Shinoda, K., "Colloidal Surfactants--Some Physicochemical Properties," p. 80. Academic Press, New York, 1963. 19. Mittal, K. L., "Micellization, Solubilization and Microemulsions," p. 9. Plenum, New York, 1977.
direct sunlight, it was found that there was a marked change in viscosity of the oil and that the exposed oil became "sticky," giving rise to a strong adhesion to surfaces of contact. A similar occurrence was observed in locations where the heating of corn oil was carried out over a period of time and the surrounding surfaces then became " s t i c k y " to the touch. They appeared to have become coated with a film of an adhesive substance. Ordinary washing with soap and water was not effective in removing the oil from such surfaces: abrasive action was required. Thus, it was thought that it would be interesting and perhaps useful to study the solubilization of corn oil. This report gives an account of the attempts to solubilize corn oil. Corn oil (Mazola, Best Foods Div., CPC International Inc., N. J.) of commercial grade was used. The nonionic surfactants used were polyoxyethylene sorbitan monolaurate, -monopalmitate, -monostearate, and -monooleate, which are water soluble, and sorbitan monolaurate, -monooleate, and -trioleate, which are oil dispersible (Honeywill-Atlas, London, England). A fixed quantity of corn oil or oily dispersion (0.01 g) containing corn oil and a sorbitan ester was added to a series of 25 ml of polysorbate solutions of increasing concentration, in graduated stoppered glass cylinders, which were allowed to rotate at 25 _+ 0.5°C in a water bath for about 6 h, The amounts of sorbitan ester added to the corn oil were such as to produce dispersions
Aqueous solutions of surfactants above the CMC have the ability to solubilize poorly water-soluble or -insoluble compounds. A literature survey shows that polysorbates (Tweens) have been used to solubilize a wide range of pharmaceutical substances including benzoic acid derivatives, essential oils, and fat-soluble vitamins (1). In addition, drugs such as sedatives, sulfonamides, analgesics, and antipyretics have also been solubilized in aqueous solutions of Tween 20 and 80 (1). Choulis (2) found that the solubilization of testosterones and amphetamines in aqueous Tween 20 and 40 solutions increased with increasing surfactant concentration above the CMC and no solubilization occurred below the CMC or when micelles were absent. In a study which involved compounds of varying polarity and nonionic surfactants, it was shown that the solubilities of the compounds studied, such as benzene, decane, and hydroxybenzoates in cetomacrogol solutions, were not adequately described solely on the basis of solubility into the separate regions of the micelle. Micellar solubility of the compounds was dependent on the hydrocarbon solubility and the presence of groups in the molecule which can form hydrogen bonds. The hydrophile-lipophile characteristics of the surface-active agent with the polarity of solubilizing molecule also affected solubilization (3). In the course of an investigation into the effect of corn oil in locations exposed to 401
Journal of Colloidand Interface Science, Vol. 78, No. 2, December 1980
0021-9797/80/120401-06502.00/0 Copyright © 1980 by Academic Press, Inc. All rights of reproduction in any form reserved.
402
LUCY
S. C. W A N
containing surfactant concentrations ranging from 5 to 40%. The presence or absence of oil droplets in the dispersion was examined under an illuminated light source. For reference, a control containing the same amount of oil as that in the test sample, but dispersed in water, was used. Solubilization of the oil or oily dispersion was considered to have occurred when the system contained a comparatively small number of oil droplets. Corn oil is highly insoluble and extremely hydrophobic. Aqueous solutions of polyoxyethylene sorbitan monooleate were used to solubilize the oil but without success. Other polysorbates, polyoxyethylene sorbitan monolaurate, -monopalmitate, and -monostearate, were also included in the study but these too were not able to solubilize the oil, despite the fact that the range of surfactant concentration used was very wide, from 0.01 to 10% (Table I). Hence a combination or mixture of surfactants was selected in an attempt to bring about solubilization. In a mixed surfactant system it is believed that solubilization is effected by the formation of mixed micelles. This has been demonstrated by evidence from cloud point determinations (4, 5) and from electrophoretic and specific conductivity measurements (6, 7). Gerbacia et al. (8) studied solubilization in an aqueous mixed micellar solution, the system being water-potassium oleate-pentanol-benzene, and found that
the major part of belizene solubilized in mixed micelles was in a relatively nonpolar environment. In a study of the binding of antihistamines to nonionic surfactants via mixed micelle formation, it was shown that mixed micelle formation was not influenced by changes in electrolyte concentration and pH, but was dependent on surfactant structure (9). In the present study, the mixed surfactants were from the sorbitan esters and polysorbates. Polyoxyethylene sorbitan esters had been used in the solubilization of simple hydrocarbons and essential oils, and the data obtained showed that the solubilizing capacities of these surfactants increased with decrease in the polyoxyethylene chain length of the homologous series (10, 11). The results obtained from this work showed that corn oil containing 5% sorbitan monooleate was not solubilized in solutions of polyoxyethylene sorbitan monooleate of varying concentrations (Table II), which were well above the CMC and therefore contained sufficient micelles to take up the oil; the CMC of polyoxyethylene sorbitan monooleate was 0.0014% as determined from surface tension measurements. It is known that solubilization can occur in one of several sites, such as inclusion into the hydrocarbon interior of the micelle or deep penetration into the palisade layer. It may also be either short penetration into the palisade layer or adsorption on t h e
TABLE
I
E x a m i n a t i o n o f A q u e o u s D i s p e r s i o n s o f P o l y s o r b a t e s t o W h i c h a F i x e d W e i g h t o f C o r n Oil w a s A d d e d , f o r t h e P r e s e n c e / A b s e n c e o f Oil D r o p l e t s a t 25°C Polysorbate concentration (%)
Polyoxyethylene sorbitan monooleate -sorbitan monostearate -sorbitan monopalmitate -sorbitan monolaurate ++,
0
0.01
0.02
0.1
0.6
1.0
2.0
5.0
9.0
10.0
++~ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
++ + + + + + +
+ + + +
l a r g e n u m b e r o f oil d r o p l e t s ; + , s m a l l n u m b e r o f oil d r o p l e t s .
Journal of Colloid and Interface Science, Vol. 78, No. 2, December 1980
LIMITING
SO LUBILIZING
403
CAPACITY
TABLE II Examination of Aqueous Dispersions of Polyoxyethylene Sorbitan Monooleate to Which was Added a Fixed Quantity of Corn Oil Containing Varying Amounts of Sorbitan Monooleate for the Presence/Absence of Oil Droplets at 25°C Corn oil + sorbitan monooleate (%) ~ +5%
Polyoxyethylene sorbitan monooleate (%) 0
0.01
0.02
0.1
0.6
1.0
2.0
5.0
9.0
10.0
++a
++
++
++
++
++
++
++
++
+
+10%
++
++
++
++
++
++
++
++
++
+
+20%
++
++
++
++
++
++
++
++
++
+
+25%
++
++
++
++
++
++
++
++
++
+
+35%
++
++
++
++
++
++
++
++
++
+
+40%
++
++
++
++
++
++
++
++
++
+
a ++, large number of oil droplets; +, smallnumber of oil droplets. surface of micelles. For nonionic surfactants, possessing polyoxyethylene groups, it has been suggested that another mode of solubilization is possible, that is, the micelle is considered to be made up of two parts, one is the inner core of hydrocarbon tails, and the other is the outer shell of hydrated polyoxyethylene (12). None of these modes of solubilization seems to be applicable to the solubilization of corn oil. It should be noted also that the sites of solubilization are not fixed. There is a rapid equilibrium between various possible sites. In addition, there is an equilibrium between the solubilized state and the free state in the aqueous medium of solubilized species (13). The locus of solubilization has been investigated as can be seen in the study of solubilization of chlorpromazine in Tween 80 solutions. The findings indicate that the locus of solubilization is principally hydrophobic (14). In the solubilization of benzoic acid derivatives in nonionic surfactant solutions, Mukerjee (15) discussed the relative importance of the hydrophobic core of the micelle and the hydrophilic exterior as the seat of solubilizing action. The distribution of the solubilizate between the two loci was shown to be related to the chemical structure of the solubilizate. It is important to understand the physical and chemical reactivities of the solubilized species. Increasing the proportion of sorbitan
ester present in the corn oil from 5% to 10, 20, 25, 35, and 40% did not effect an appreciable amount of solubilization (Table II). Similar observations were noted for oil containing sorbitan monolaurate and also for that containing the trioleate ester under the same conditions. Aqueous solutions of the other polysorbates, that is, polyoxyethylene sorbitan monolaurate, -monopalmitate, and -monostearate, were also employed to solubilize the oil. But oil droplets in as large a number as that in the control were clearly visible in these dispersions. It would seem, therefore, that the mixed surfactants were not able to solubilize the oil. Micellar weight in aqueous solutions of polyoxyethylene-type nonionic surfactants increases and the CMC decreases with increase in temperature and this change in micellar weight in nonionic surfactant solutions containing a solubilizate has been studied by Nakagawa et al. (16). The greater the micellar weight, the greater is the number of solubilizate molecules per micelle and hence the amount solubilized increases with increasing temperature. Studies of solubilization of griseofulvin in nonionic surfactant solutions at temperatures ranging from 25 to 37.5°C showed that solubilization of the antibiotic increased with increasing temperature (17). However, in this study, increasing the temperature Journal of Colloid and Interface Science, Vol. 78, No. 2, December 1980
404
L U C Y S. C. W A N
from 25°C to 35, 45, 60, 80, and 90°C was of no effect on the solubilization of the oil. Just as in the control, a large number of oil droplets were found in all dispersions at these temperatures. Extending the period of rotation in the water bath from 4 to 6 hr and for a further period of up to 8 hr as well as applying more vigorous agitation to disperse the oily mixture in the aqueous solution by means of increasing the speed of rotation in the bath did not produce a significant reduction in the number of oil droplets in the system. All these factors which can assist solubilization have failed to solubilize corn oil. Similar experiments were carried out for corn oil exposed to sunlight and the results obtained were the same, in that exposed corn oil could not be solubilized by either solutions of polysorbates or by a combination of surfactants in the system. Since interaction between the surfactants in both phases is likely to occur at the interface, it was considered necessary to determine whether this interfacial activity would
exert any influence on the solubilization study. The surface or interfacial tension of various systems was measured using the Du Nouy tensiometer at 25°C (Cambridge Instrument Co., England) under standardized conditions of equilibration for aging effects. The oil and aqueous phases were allowed to come into contact for about 4 hr before measurement was begun. The ring was allowed to remain at the interface for a period of 30 min before being detached from the interface to make the measurement. This period of time was found to be suitable from preliminary experiments. Figure 1 shows the change in the interfacial tension between corn oil containing a fixed amount of sorbitan monooleate and solutions of pol yoxyet hyl ene sorbitan monooleate of varying concentrations. The pattern of behavior with respect to the lowering of the interfacial tension was not different from that seen with aqueous solutions of the same polysorbate (Fig. 2). A higher concentration of the oil-soluble surfactant produced a greater depression of
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LIMITING SOLUBILIZING CAPACITY
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FIG. 2. Surface/interfacial tension curves for air/surfactant solution, air/corn oil, and corn oil/water systems in which surfactant is present or absent in one or both phases at 25°C. Dashed curves, polyoxyethylene sorbitan monooleate (PSM) in water; solid curves, sorbitan monooleate (SM) in oil; (O) PSM in water; (A) SM in corn oil; (©) SM in corn oil/water; (×) corn oil/PSM in water. the interfacial tension. Although the quantities of surfactant, both in the oil phase and in the aqueous phase, were m u c h less than those used in the solubilization study, nevertheless, the low interfacial tension attained in these s y s t e m s shows that solubilization of corn oil was not facilitated b y this condition existing at the interface. Similar results were obtained for corresponding systems in which either sorbitan monolaurate or the trioleate ester was added to the oil phase. It was o b s e r v e d that with high surfactant concentrations such as those used in the solubilization studies, there was a t e n d e n c y for spontaneous emulsification to
o c c u r at the interface, in which case the interfacial tension was reduced to such an extent that the ring was readily detached f r o m the interface. The surface tension o f corn oil containing varying a m o u n t s of sorbitan ester did not change with increasing concentration of the surfactant; there was no sharp b r e a k in the graph plotted as shown in Fig. 2, which is in contrast to that d e m o n s t r a t e d by aqueous solutions o f the c o r r e s p o n d i n g watersoluble surfactant. This indicates that there is no micellization. It is known, h o w e v e r , that micelles can be f o r m e d in n o n a q u e o u s solvents but these are mainly h y d r o c a r b o n s Journal of Collold and Interface Seience, VoI. 78, No. 2, December 1980
406
LUCY S. C. WAN
or solvents whose solvent properties are similar to those of the hydrocarbons (18). In the case of micelle formation in nonaqueous media, the solvophobic interactions of surfactants in nonaqueous media are weaker than those involving micelles in aqueous solutions. In solvents which are highly nonpolar, the polar groups of the surfactants become solvophobic and in such solvents, aggregates form in which the polar groups form the core. These are termed inverse, reverse, or reverted micelles. The aggregation properties of surfactants in nonaqueous media may be altered greatly by the presence of traces of water or other additives. The general problems of the different patterns of self-association and the need for cooperativity for the existence ofa CMC are the same for nonaqueous media as for aqueous media (19). It is not known whether micelles can be formed in oil. Data on the interfacial tension of liquid/liquid systems were also included in Fig. 2 for comparison with those of the air/liquid systems. It is seen that there is a marked depression of the interracial tension when the air phase is replaced by an oil phase. To summarize, the results of this investigation show that corn oil is not solubilized by either aqueous solutions of polyoxyethylene sorbitan esters or by a combination of these surfactants with sorbitan esters. Although the presence of a surfactant in the solubflizate lowers the interfacial tension between the solubilizate and the solubilizer, it is not able to bring about solubilization of a difficult solubilizate such as corn oil. The general statement that surfactants which form micelles are able to solubilize water-insoluble compounds is perhaps not as widely applicable as is commonly believed. The findings suggest that
Journal of Colloidand Interface Science, Vol. 78, No. 2, December1980
nonionic surfactants of the polyoxyethylene sorbitan ester type as well as the sorbitan esters have limiting capacities to solubilize extremely hydrophobic substances such as corn oil. REFERENCES 1. Sj6blom, L., "Solvent Properties of Surfactant Solutions" (K. Shinoda, Ed.), p. 189. Arnold, London, 1967. 2. Choulis, N. H., Pharmazie 28, 376 (1973). 3. Corby, T. C., and Elworthy, P. H., J. Pharm. Pharmacol. 23, 395 (1971). 4. Maclay, W. N., J. Colloid Sci. 11,272 (1956). 5. Kuriyama, K., Inoue, H., and Nakagawa, T., Kolloid Z. 183, 68 (1962). 6. Nakagawa, T., and Inoue, H., Nippon Kagaku Zasshi 78, 636 (1957). 7. Tokiwa, F., and Moriyama, N., J. Colloid Interface Sci. 30, 338 (1969). 8. Gerbacia, W. E., Rosano, H. L., and Zajac, M., J. Amer. Oil Chem. Soc. 53, 101 (1976). 9. Thoma, K., and Siemen, E., Pharm. Ind. 38, 193 (1976). 10. Sj6blom, L., "Solvent Properties of Surfactant Solutions" (K. Shinoda, Ed.), p. 200. Arnold, London, 1967. 11. Gluzman, R. G., and Lyashenko, S. S., Farmatsiya (Moscow) 17, 11 (1968). 12. Nagakawa, T., "Nonionic Suffactants" (M. J. Schick, Ed.), p. 558. Arnold, London, 1967. 13. Mittal, K. L., "Micellization, Solubilization and Microemulsions," p. 11. Plenum, New York, 1977. 14. Nguyen, D. P., and Paiement, J., Canad. J. Pharm. Sci. 7, 117 (1972). 15. Mukerjee, P., J. Pharm. Sci. 60, 1528 (1971). 16. Nakagawa, T., Kuriyama, K., and Inoue, H., in "12th Symposium on Colloid Chemistry," p. 32. Chem. Soc. Japan, 1959. 17. Kassem, A. A., and Mursi, N. M., Bull. Fac. Pharm. Cairo Univ. 9, 11 (1970). 18. Shinoda, K., "Colloidal Surfactants--Some Physicochemical Properties," p. 80. Academic Press, New York, 1963. 19. Mittal, K. L., "Micellization, Solubilization and Microemulsions," p. 9. Plenum, New York, 1977.