Effect of Adding Isopropyl Myristate to Microemulsions Based on

Astra Ha¨ssle AB, S-431 83 Mo¨lndal, Sweden, and Physical Chemistry 1, University ... in-water type of structure at low concentrations of IPM to an ...
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Langmuir 1998, 14, 3506-3511

Effect of Adding Isopropyl Myristate to Microemulsions Based on Soybean Phosphatidylcholine and Triglycerides Christian von Corswant*,† and Olle So¨derman‡ Astra Ha¨ ssle AB, S-431 83 Mo¨ lndal, Sweden, and Physical Chemistry 1, University of Lund, P.O. Box 124, S-221 00 Lund, Sweden Received November 14, 1997. In Final Form: March 25, 1998 The effect on the phase behavior and microstructure of pharmaceutically interesting microemulsions which is produced by adding isopropyl myristate (IPM) to the systems is described. The microemulsions are based on water, 1-propanol, soybean phosphatidylcholine (SbPC), and two different triglycerides; a medium-chain triglyceride (C8-C10) and a long-chain triglyceride (soybean oil). When IPM was added to the triglyceride oil phase, the spontaneous curvature of the surfactant film decreased and the flexibility of the surfactant monolayer increased. The change in spontaneous curvature was manifested by a gradual change in the microstructure of the microemulsion, as revealed by NMR self-diffusion data, from an oilin-water type of structure at low concentrations of IPM to an oil continuous structure at higher IPM concentrations. At intermediate IPM concentrations, the microstructure was found to be of a bicontinuous nature. By optimizing the amount of IPM and the 1-propanol concentration, one-phase microemulsions containing equal amounts of water and oil can be obtained at lower surfactant concentrations and lower 1-propanol concentrations, compared with those for a system with only the triglyceride as the nonpolar phase.

1. Introduction A microemulsion is defined as a system of water, oil, and surfactant which is a single, optically isotropic and thermodynamically stable solution. These unique properties make microemulsions interesting for many applications, and there is currently a great deal of interest in developing microemulsions based on nontoxic components for pharmaceutical use. One of the few surface active substances that is generally considered to fulfill these criteria is soybean phosphatidylcholine (SbPC), as phosphatidylcholine is a natural component of most cell membranes.1 For the same reason the choice of suitable oils is also limited and triglycerides or fatty acid monoesters such as isopropyl myristate (IPM) are preferred. There are two important parameters which describe the ability and effectiveness of a surfactant to form microemulsions, the spontaneous curvature H0 and the flexibility of the surfactant film it forms.2,3 The flexibility of the surfactant film is often quantified in terms of the bending moduli κ and κj. H0, which is the curvature an unconstrained film would adopt, depends both on the nature of the surfactant and on the composition of the polar and nonpolar phases. H0 is defined as positive when the film curves around the oil. It is favorable to keep the surfactant concentration in the microemulsion at a minimum for toxicological reasons, and this can be achieved by matching H0 with the volume fraction Φ0 of oil/(oil + water). Thus, for Φ0 ) 0.5, H0 should be zero, while, for Φ0 > 0.5, H0 should be negative and, for Φ0 < 0.5, H0 should be positive. * To whom correspondence should be addressed. † Astra Ha¨ssle AB. E-mail: christian.corswant@ hassle.se.astra.com. ‡ University of Lund. (1) Attwood, D. In Colloidal Drug Delivery Systems; Kreuter, J., Ed.; Marcel Dekker: New York, 1994; Vol. 66, pp 31-71. (2) Daicic, J.; Olsson, U.; Wennerstro¨m, H. Langmuir 1995, 11, 24518. (3) Olsson, U.; Wennerstro¨m, H. Adv. Colloid Interface Sci. 1994, 49, 113-46.

SbPC is known as an almost balanced surfactant; that is, H0 is close to zero,4 and it has recently been shown that it is possible to form microemulsions based on SbPC and triglycerides, using 1-propanol to modify H0 and increase the flexibility of the SbPC film.5-7 In the present study, we have investigated the opportunity to tune the spontaneous curvature of the SbPC film by adding IPM to the triglyceride oil phase in order to minimize the surfactant and 1-propanol concentration in the microemulsion. Two triglycerides, one mediumchain triglyceride (MCT) and one long-chain triglyceride (LCT), soybean oil, were studied. 2. Experimental Section 2.1. Materials. Soybean phosphatidylcholine, SbPC (Epicuron 200), was obtained from Lucas Meyer Co., Germany. The chain-length distribution of the fatty acids in Epicuron 200 is as reported: C16:0 ) 13.3%, C18:0 ) 3%, C18:1 ) 10.2%, C18:2 ) 66.9%, and C18:3 ) 6.6%.4 The medium-chain triglyceride, MCT (Miglyol 810N), was purchased from Hu¨ls, Germany. According to the manufacturer, the chain-length distribution of the fatty acids was C6:0 e 2%, C8:0 ) 70-80%, C10:0 ) 18-28%, and C12:0 e 2%. 1-Propanol and isopropyl myristate (98%) were supplied by Aldrich (Steinheim, Germany), and soybean oil was purchased from Sigma, St. Louis. All the reagents were used as received. The water used was first purified by reverse osmosis and then further treated in a primary and secondary ion-exchange pack with a photooxidation step in between and finally passed through an ultra-microfiltration unit (Elgastat maxima-HPLC, ELGA Ltd, U.K.). The quality of the water was checked by measuring the conductance and the surface tension. (4) Shinoda, K.; Araki, M.; Sadaghiani, A.; Khan, A.; Lindman, B. J. Phys. Chem. 1991, 95, 989-93. (5) von Corswant, C.; Engstro¨m, S.; So¨derman, O. Langmuir 1997, 13, 5061-5070. (6) Leser, M. E.; Vanevert, W. C.; Agterof, W. G. M. Colloids Surf., 1996, 116, 293-308. (7) Aboofazeli, R.; Patel, N.; Thomas, M.; Lawrence, M. J. Int. J. Pharm. 1995, 125, 107-16.

S0743-7463(97)01248-1 CCC: $15.00 © 1998 American Chemical Society Published on Web 06/03/1998

Effect of Adding Isopropyl Myristate to Microemulsions

Langmuir, Vol. 14, No. 13, 1998 3507 glass capillary with deuterated DMSO was placed in the NMR tube to produce a lock signal. The self-diffusion coefficients were calculated by fitting the Stejskal-Tanner equation to the obtained peak heights11 using a nonlinear, least-squares procedure. To account for the fast proton exchange between water and 1-propanol in the aqueous phase, the procedure according to ref 5 was followed.

3. Results and Discussion

Figure 1. Volume fractions of different phases of systems with three different oils, (a) MCT, (b) LCT, and (c) IPM, as a function of the 1-propanol concentration (δ): γ ) 7.5 wt %; 25.0 °C. 2.2. Phase Diagrams. All the phase diagrams were constructed and analyzed as described previously.5 The different phases observed in all the presented phase diagrams were noted as follows: W, a clear aqueous phase; We, a turbid aqueous phase consisting of either an o/w emulsion or a dispersed lamellar phase or a combination of both; Lc, a liquid crystalline phase; Me, a microemulsion phase characterized by low viscosity, optical isotropic behavior, and a translucent appearance (No distinction between o/w, w/o, or bicontinuous type microemulsions was made.); O, a clear oil phase. The phase diagrams in Figures 1 and 2 can be regarded as pictures of the relative volumes of the different phases which appear in each vial in a series of samples where the total volume in each vial is normalized to 1. 2.3. PFG-NMR Measurements. The pulsed field gradient nuclear magnetic resonance technique8,9 was used to determine the different self-diffusion coefficients of the components at 25 ( 0.5 °C by monitoring the 1H signal on a Varian 400 MHz spectrometer. A stimulated echo with a longitudinal eddy current delay (LED) pulse sequence10 was used to minimize j-modulation effects and phase errors due to eddy currents induced by the gradients. In the experiments, the length of the gradient pulse was kept constant at 5.0 ms and the gradient strength was varied between 3 and 50 G/cm. The time between the gradient pulses (∆) was 140 ms and the time between the first two radio frequency pulses (τ) was 40 ms. The gradient strength was calibrated by measuring the self-diffusion coefficient of small amounts of H2O in D2O. Since H2O was used in the microemulsions, a sealed (8) Stilbs, P.; Moseley, M. E. Chem. Scr. 1980, 15, 176. (9) Stilbs, P. Prog. Nucl. Magn. Reson. Spectrosc. 1987, 19, 1-45. (10) Gibbs, S. J.; Johnsson, C. S., Jr. J. Magn. Reson. 1991, 93, 391.

3.1. Phase Behavior. The nomenclature in the description of the phase behavior is based on the one used by Kahlweit and co-workers.12,13 The weight fraction of oil in the oil/water mixture is denoted R and defined as (triglyceride + IPM)/(triglyceride + IPM + water), the weight fraction of IPM in the oil phase is denoted β and is defined as IPM/(IPM + triglyceride), and the total concentrations of 1-propanol and SbPC are expressed as the percentage by weight of the total mixture and are denoted δ and γ respectively. In Figure 1, the effect of 1-propanol concentration on the phase behavior of the MCT, LCT, and IPM systems at R ) 0.5 and γ ) 7.5 wt % is shown. The MCT system (Figure 1a) has been described in detail earlier.5 At low δ, a Lc phase is in equilibrium with a W and an O phase and very stable emulsions are formed. When δ is increased, the Lc phase incorporates the water and, at a certain concentration of 1-propanol (12-13 wt %) the Lc phase is destabilized and a middle-phase microemulsion, that is, a Winsor III system, is formed. When δ is increased still further, the microemulsion phase gradually incorporates more water and expels the oil and at 18 wt % 1-propanol an o/w microemulsion in equilibrium with an excess oil phase, that is, a Winsor I system, is formed. The change in phase behavior caused by the addition of 1-propanol can, in terms of film properties, be interpreted as an increased flexibility of the surfactant film, since the Lc phase is destabilized in favor of a microemulsion phase and an increase of H0 (1-propanol decreases the polarity of the aqueous phase). In the LCT system, no swelling of the lamellar liquid crystalline phase and formation of a Winsor III system was observed. Instead, a Winsor I system was formed directly. The lamellar liquid crystalline phase in the MCT and LCT systems is destabilized at approximately the same 1-propanol concentration (12-13 wt %). This implies that the differences in H0 revealed in Figure 1a and b (close to zero for MCT and more positive for LCT) are mainly due to the ability of the triglycerides to penetrate the hydrocarbon chains of SbPC, and this consequently suggests that the interaction between the surfactant film and the triglyceride is decreased as the hydrocarbon chain length of the triglyceride increases. In the IPM system (Figure 1c), a w/o microemulsion in equilibrium with an excess water phase, that is, a Winsor II system, was formed over the entire 1-propanol concentration range which was studied, and it is evident that, with IPM as the nonpolar phase, H0 is negative. Furthermore, the microemulsion phase was formed at a lower 1-propanol concentration compared with that for the triglycerides. This different phase behavior is most probably due to a high degree of interaction between the oil and the nonpolar parts of the surfactant film. This is (11) Stejskal, E. O.; Tanner, J. E. J. Chem. Phys. 1965, 42, 288-292. (12) Kahlweit, M.; Strey, R.; Haase, D.; Kunieda, H.; Schmeling, T.; Faulhabe, B.; Borkovec, M.; Eicke, H. F.; Busse, G.; Eggers, F.; Funk, T.; Richmann, H.; Magid, L.; So¨derman, O.; Stilbs, P.; Winkler, P.; Dittrich, A.; Jahn, W. J. J. Colloid Interface Sci. 1987, 118, 436-53. (13) Kahlweit, M.; Strey, R. J. Phys. Chem. 1987, 91, 1553-7.

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Figure 2. Volume fractions of different phases for the MCT and LCT system as a function of the IPM concentration of the oil phase: (a) MCT, 13 wt % 1-propanol, and 19 wt % 1-propanol; (b) LCT, 13 wt % 1-propanol, and 19 wt % 1-propanol; γ ) 7.5 wt %; 25.0 °C.

known to decrease H0 and increase the flexibility of the film. The suggested explanation is further supported by the fact that SbPC was found to be soluble in IPM. When water was added to this solution, an L2 phase was formed with reological properties similar to those described for hydrocarbon solvents such as isooctane and cyclohexane where a dramatic increase in viscosity with increasing water concentration has been reported.14 The increase in viscosity has, in the case of isooctane and cyclohexane, been explained by the formation of a network of giant polymer-like reverse micelles. In Figure 2, the phase behavior at constant δ (13 and 19 wt %) and varying β for both MCT and LCT is shown. It is evident that the addition of IPM to both MCT and LCT induced a change in the microstructure of the microemulsion from an o/w type (bicontinuous for the 13 wt % MCT system5) to a w/o type. Increased penetration of the surfactant film decreases the spontaneous curvature from slightly positive values to negative values. The balanced state (when H0 is equal to zero) is assumed to be reached when the excess volume fractions of the oil and water phases are equal, and the weight fraction of IPM needed to reach this state is determined from the phase diagrams and is denoted β*. With this assumption the volume fractions of the nonpolar phase and the aqueous phase are taken to be equal and independent of β. The validity of this assumption was checked by measuring the volume fractions of the oil phase and the aqueous phase for the quaternary system water/1-propanol/MCT/ IPM at three different β values: viz. β ) 0, β ) 0.2, and β ) 1 for the system with 13 wt % 1-propanol and β ) 0, β ) 0.25, and β ) 1 for the system with 19 wt % 1-propanol. The volume fractions of the oil phases were found to be 0.494, 0.499, and 0.519 for the 13 wt % 1-propanol system and 0.483, 0.494, and 0.530 for the 19 wt % 1-propanol system. β* for the MCT system was found to be 0.08 at 13 wt % 1-propanol and 0.24 at 19 wt % 1-propanol. For (14) Schurtenberger, P.; Cavaco, C. Langmuir 1994, 10, 100-108.

the LCT system, β* ) 0.58 at 13 wt % 1-propanol and 0.71 at 19 wt % 1-propanol. The results show that β* is considerably lower for MCT compared with LCT, which leads to the same conclusion as that resulting from the analysis of Figure 1, that is, MCT has a more pronounced interaction with the hydrophobic part of the surfactant film than LCT. Furthermore, SbPC is less effective in solubilizing LCT compared with MCT, as the volume fraction of the balanced microemulsion is smaller for the former than for the latter. In Figure 3, the phase behavior of the MCT system at constant R ) 0.5 and β ) 0.08 is shown. The most striking features in Figure 3 are the fact that the one-phase microemulsion region goes below the two-phase area Me + W and the lack of symmetry around a horizontal line which goes through the “tail of the fish”, that is, the point at which the three-phase region is connected with the one-phase region. This plane of symmetry is believed to be a general feature of nonionic systems where the temperature is used as the tuning parameter, and it is due to the fact that H0 varies linearly with temperature around the balanced state.15 The different behavior in the system presented in Figure 3 is related to the fact that the addition of 1-propanol increases H0 and decreases the bending moduli. An increase in flexibility decreases the solubilization capacity of the microemulsion phase,2 and consequently both water and oil are expelled from the microemulsion as the 1-propanol concentration increases. The simultaneous increase in H0 leads to the expulsion of oil and the incorporation of water. The net effect of an increase in δ is a rapid increase in the excess oil phase, while the excess water phase first increases as a result of the decreasing solubilization capacity and then increases again because of the change in curvature in the microemulsion phase. This is illustrated in the inset in Figure 3, where the volume fractions of the different phases are shown for γ ) 11 wt % as a function of δ. (15) Strey, R. Colloid Polym. Sci. 1994, 272, 1005-1019.

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Langmuir, Vol. 14, No. 13, 1998 3509

Figure 3. Phase behavior of the system water/1-propanol/SbPC/MCT/IPM at constant R ) 0.5 and β ) 0.08. Temperature: 25 °C. The inset shows the volume fractions of the different phases at 11 wt % SbPC. The dashed lines illustrates that there are several narrow two- and three-phase regions between the O + Lc + W region and the Me + W and Me regions.

Another important observation in Figure 3 is that, by balancing the microemulsion with the addition of IPM, the concentrations of both 1-propanol and SbPC needed to form a one-phase system are reduced compared with the situation when only MCT is used as the oil phase (Figure 7d in ref 5). For the balanced microemulsion in Figure 3, a one-phase microemulsion is obtained at 10.9 wt % 1-propanol and 11.0 wt % SbPC. The corresponding figures for a pure MCT system are 11.6 wt % 1-propanol and 12.5 wt % SbPC.5 3.2. Microstructure. The self-diffusion coefficients of each individual component in the microemulsion formed in Figure 2a were determined by the PFG-NMR technique in order to define the microstructure of the microemulsion.16,17 The absolute values are presented in Figure 4, and the relative self-diffusion coefficient for water, Dw/ Dw° (the observed value divided by the value of the self(16) Lindman, B.; Olsson, U. Ber. Bunsen-Ges. Phys. Chem. 1996, 100, 344-63. (17) Lindman, B.; Shinoda, K.; Olsson, U.; Anderson, D. M.; Karlstro¨m, G.; Wennerstro¨m, H. Colloids Surf. 1989, 38, 205-24.

diffusion coefficient of water in a binary mixture of water and 1-propanol at appropriate concentrations), is shown in Figure 5. For an oil-in-water microemulsion, Dw/Dw° is close to 1 and for a water-in-oil structure, Dw/Dw° is usually below 0.1. In the bicontinuous case, the relative self-diffusion coefficient is high for both water and oil (∼1/2). For the system containing 19 wt % 1-propanol, Dw/Dw° is close to 1 in the Winsor I region, that is for β between 0 and 0.05. Furthermore, DMCT is equal to DSbPC. These findings clearly indicate that, in this region of the phase diagram, the surfactant predominantly forms oil-in-water aggregates. On the other hand, at high IPM concentrations, where we have a Winsor II system (β > 0.33), Dw/ Dw° has decreased to about 0.2 and does not change much with β, while DMCT and DIPM have increased and are considerably higher compared with DSbPC. This indicates a microstructure with a curvature toward water. For the Winsor III system formed between β ) 0.05 and 0.33, Dw/Dw° decreased from 0.8 to 0.2, while both DMCT and DIPM increased and DSbPC was constant. This general

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spontaneous curvature of the surfactant monolayer and gradually changes the microstructure of the system from an oil-in-water structure to a water-in-oil structure, with a bicontinuous structure with a spontaneous curvature close to zero formed at intermediate IPM concentrations. The microemulsion phase of the Winsor III system of MCT containing 13 wt % 1-propanol and no IPM has been shown to be of a bicontinuous nature.5 As can be seen from Figure 4a, the addition of IPM reduced Dw and increased both DIPM and DMCT. Dw/Dw° was found to be 0.5 at β*. This value is close to the theoretical value for a minimal surface with an infinitely thin film which has been calculated to about 2/3.18 For both systems, the values of Dw were, however, considerably higher than DSbPC, even when the oil phase contained only IPM. For a true water droplet structure, Dw ≈ DSbPC would be expected. To analyze the microstructure of the microemulsion formed with only IPM and δ ) 13 wt % in more detail, a w/o microemulsion with spherical water droplets covered with a monolayer of SbPC was assumed. It is possible to calculate the mean droplet radius from simple geometrical constraints using

Rw ) 3Φw/Afilm

Figure 4. Self-diffusion coefficients for water (open circles), MCT (filled triangles), IPM (open triangles), and SbPC (open squares). (a) 13 wt % 1-propanol; (b) 19 wt % 1-propanol. Samples were taken from the microemulsion phase shown in Figure 2a. The dotted vertical lines indicate where the phase transitions between Winsor I (W I), Winsor (W III), and Winsor II (W II) systems occurs.

where Φw is the volume fraction of the dispersed water phase (water and 1-propanol) and Afilm is the interfacial area per unit volume of the surfactant monolayer. The total water content of the microemulsion was determined to be 12.6 wt %, and the water content of the IPM phase with the same proportions of water, 1-propanol, and IPM but without SbPC was found to be 0.98 wt %. The concentration of 1-propanol in the water phase of this system was determined to be 17.0 wt %. Assuming that all the SbPC (Mw: 773 g/mol) is in the L2 phase and that the area/SbPC molecule (ASbPC) is 60 Å2/molecule,19 Rw was calculated to be 88 Å. Rw is the radius of the droplet at the interface between the water phase and the polar part of SbPC. To obtain the hydrodynamic radius (which is the appropriate radius to use with the diffusion measurements) of the droplet, the thickness of the surfactant layer should be added to Rw. On average, every droplet is surrounded by Adroplet/ASbPC or 4π(88)2/60 ) 1629 molecules of SbPC. Using the molecular volume for SbPC of 1267 Å3/molecule,19 the volume of the SbPC layer that covers each droplet can be calculated to be 1629 × 1267 ) 2.064 × 106 Å3. The total volume of the droplet can then easily be calculated using the radius of the water droplet and the volume of the SbPC shell, and this gives a hydrodynamic droplet radius of 106 Å. The diffusion coefficient at infinite dilution, D0, of the droplet can be calculated using the Stokes-Einstein equation:

D0 )

Figure 5. Relative self-diffusion coefficients Dw/Dw° (the observed value divided by the value of the water phase at the appropriate 1-propanol concentration) for water in the microemulsion phase shown in Figure 4a (open circles) and Figure 4b (filled triangles).

pattern of the self-diffusion coefficients together with the phase behavior strongly suggests that exchanging MCT with IPM increases the interaction between the oil phase and the nonpolar parts of SbPC which decreases the

kBT 6πηRH

where kB is the Boltzmann constant, T is the temperature in Kelvin, η is the viscosity of the medium and RH is the hydrodynamic radius. At 25 °C, the viscosity of the IPM/ 1-propanol solution without SbPC was measured as 5.5 mPa s. As noted above, the Stokes-Einstein equation is only valid for infinitely dilute aggregates, and at finite concentrations, aggregate obstruction effects have to be (18) Anderson, D. M.; Wennerstro¨m, H. J. Phys. Chem. 1990, 94, 8683-94. (19) Small, D. M. The physical chemistry of lipids, 2nd ed.; Plenum Press: New York, 1986; Vol. 4.

Effect of Adding Isopropyl Myristate to Microemulsions

considered. These are usually written as an expansion in the volume fraction φagg of aggregates. To first order in φagg, we have

D ) D0(1 - kφagg) where k is an expansion coefficient the value of which depends on the shape of the particle and the degree of hydrodynamic interaction present. For hard spheres with no hydrodynamic interaction, k is equal to 2. Using this value of k and the appropriate value of φagg ) 0.25, the self-diffusion coefficient for the water droplets was calculated to be 1.9 × 10-12 m2/s. Since the diffusionNMR technique measures root-mean-square displacements over macroscopic distances (typically over several micrometers), the measured self-diffusion coefficient for water should be close to the calculated value of the droplet if the hypothesis relating to hard spheres is true. The measured value for water was 8.7 × 10-11 m2/s, which is a factor of 50 higher than that predicted by the model. The measured value is, however, an average of the diffusion of the water in the droplets and the free water dissolved in the IPM phase. The fraction of free water molecules which would produce the observed value can be calculated using a simple two-site exchange model:

Dobs ) pDfree + (1 - p)Dd where Dobs is the observed self-diffusion constant for water, p is the fraction of free water, Dfree is the self-diffusion constant of free water in the IPM phase, and Dd is the self-diffusion constant of the water droplets. Dfree can be estimated from the relationship Dfree ) DH2OηH2O/ηIPM (derived from the Stokes-Einstein equation, assuming the same RH for water in neat water and in the IPM phase) to be 3.7 × 10-10 m2/s. Using the calculated value of 1.9 × 10-12 m2/s for Dd, p is calculated to be 0.23, which should be compared with the value obtained from the determinations of the water concentration in the IPM phase and in

Langmuir, Vol. 14, No. 13, 1998 3511

the droplets, which produce a value for p of 0.06. Although there is a certain degree of uncertainty in these calculations, this uncertainty cannot account for the difference. Instead, the observed self-diffusion coefficients clearly imply that some additional transportation process for the water is involved. The exact nature of this mechanism is unknown, but we suggest that some sort of clusters forms, in which the transportation of water between the droplets is facilitated by some attractive force between the droplets. Mechanisms of this kind have been discussed by Olsson et al.3 4. Conclusions In this work, the effect of adding IPM to microemulsions based on SbPC and two different triglycerides has been studied. The main conclusion is that IPM can readily be used to tune the spontaneous curvature of the surfactant monolayer and that the addition of IPM also increases the flexibility of the surfactant film. Both effects are probably due to an increased interaction of IPM with the hydrocarbon chains of SbPC. The decrease in H0 following the addition of IPM is supported by both the phase behavior and the self-diffusion NMR study. The selfdiffusion coefficients demonstrate a continuous change in microstructure from oil-swollen micelles over a bicontinuous structure to a more oil-continuous structure, although the self-diffusion of water at high concentrations of IPM was too high to be compatible with a classical reversed micellar structure. By optimizing the amount of IPM and the 1-propanol concentration, one-phase microemulsions containing equal amounts of water and oil can be obtained at lower surfactant concentrations and lower 1-propanol concentrations compared with those for a system with only the triglyceride as the nonpolar phase. Acknowledgment. P. Thore´n is thanked for technical assistance with the phase diagrams. LA971248D