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Langmuir 2002, 18, 26-30
Formation and Stability of Nano-Emulsions Prepared Using the Phase Inversion Temperature Method P. Izquierdo,† J. Esquena,† Th. F. Tadros,‡ C. Dederen,‡ M. J. Garcia,†,§ N. Azemar,† and C. Solans*,† Department de Tecnologia de Tensioactius, Institut d’Investigacions Quı´miques i Ambientals de Barcelona, CSIC, Jordi Girona 18-26, 08034-Barcelona, Spain, UNIQEMA, Everslaan 45, B-3078 Everberg, Belgium, and Department de Farmacia i Tecnologia Farmace` utica, Universitat de Barcelona, Avda. Joan XXIII s/n. 08028-Barcelona, Spain Received June 1, 2001. In Final Form: September 17, 2001 Formation of O/W nano-emulsions has been studied in water/C h 12E h 4/oil systems by the phase inversion temperature emulsification method. Emulsification was carried out at the corresponding HLB (hydrophiliclipophilic balance) temperature, and then the emulsions were cooled fast to 25 °C. The influence of surfactant concentration and oil solubility on HLB temperature, nano-emulsion droplet size, and stability has also been studied. Droplet size was determined by dynamic light scattering, and nano-emulsion stability was assessed, measuring the variation of droplet size as a function of time. The results obtained showed that the breakdown process of nano-emulsions studied could be attributed to Ostwald ripening. An increase of nano-emulsion instability with the increase in surfactant concentration and oil solubility was also found.
Introduction Nano-emulsions are a class of emulsions that can be transparent or translucent (size range 50-200 nm) or “milky” (up to 500 nm).1-5 Unlike microemulsions, which are transparent and thermodynamically stable,6-8 nanoemulsions are only kinetically stable. However, the longterm physical stability of nano-emulsions (with no apparent flocculation or coalescence) makes them unique, and they are sometimes referred to as “approaching thermodynamic stability”. The inherent long-term physical stability of nanoemulsions can be well understood from a consideration of their stabilization. In most cases nano-emulsions are prepared using nonionic surfactants of the ethoxylated type, which may be considered as an A-B “diblock”. The alkyl chain (A-chain) resides in the oil phase, leaving the poly(ethylene oxide) (PEO), B-chain, “dangling” in solution. The B-chain has a thickness δ that depends on the number of EO units; in most cases δ is in the range 5-10 nm. In other words, the ratio of adsorbed layer thickness to droplet radius (δ/r) is significant. This means that the system will be sterically stabilized providing that the polymeric chains are in a good solvent.9 * To whom correspondence should be addressed. E-mail: csmqci@ cid.csic.es. Fax: 34-93-2045904. Phone: 34-93-4006159. † Institut d’Investigacions Quı´miques i Ambientals de Barcelona. ‡ UNIQEMA. § Universitat de Barcelona. (1) Lee, G. W. J.; Tadros, Th. F. Colloids Surf. 1982, 5, 105-115. (2) Sagitani, H. In Organized Solutions; Friberg, S. E., Lindman, B., Eds.; Marcel Dekker: New York, 1992; pp 259-271. (3) Sudol, E. D.; El-Aasser, M. S. In Emulsion Polymerization and Emulsion Polymers; Lovell, P. A., El-Aasser, M. S., Eds.; Wiley & Sons: New York, 1997; pp 699-722. (4) Nakajima, H. In Industrial Applications of Microemulsions; Solans, C., Kunieda, H., Eds.; Marcel Dekker: New York, 1997; pp 175-197. (5) Forgiarini, A.; Esquena, J.; Gonza´lez, C.; Solans, C. Langmuir 2001, 17 (7), 2076-2083. (6) Hoar, T. P.; Schulman, J. H. Nature 1943, 152, 102. (7) Ruckenstein, E.; Chi, J. C. J. Chem. Soc., Faraday Trans. 1960, 71, 2. (8) Overbeek, J. Th. G. Faraday Discuss. Chem. Soc. 1978, 65, 7. (9) Napper, D. H. Polymeric Stabilization of Colloid Dispersions; Academic Press: London, 1983.
The attraction of nano-emulsions for application in various industrial fields,10-14 for example, reaction media for polymerization, personal care and cosmetics, health care, and agrochemicals, is due to the following reasons. First, the very small droplet size causes a large reduction in the gravity force and the Brownian diffusion may prevent any creaming or sedimentation. Second, the steric stabilization prevents any flocculation or coalescence of the droplets. The small droplet size and the high kinetic stability make nano-emulsions suitable for efficient delivery of active ingredients (due to their large surface area) and for penetration through the “rough” texture of the skin.15 Unlike microemulsions, which require a high concentration of surfactants for their preparation (usually in the range 10-30 wt %), nano-emulsions can be prepared at moderate surfactant concentration (in the range 4-8 wt %). Despite the above advantages, only a few systematic studies have been carried out on the mechanism of formation of nano-emulsions and their long-term physical stability.5,16-21 In this paper, we will report some preliminary results on the formation of nano-emulsions using (10) U.S. Patent 5098606, 1992. (11) Fo¨ester, T.; Heinen, S.; Heide, B. Ger Offen DE 19532543 A1, 6 Mar 1997, 8 pp. (12) Restle, S.; Cauwet-Martin, D. Eur. Pat. Appl. EP 842652 A1, 20 May 1998, 12 pp. (13) Jon, D. I.; Prettypaul, D. I.; Benning, M. J.; Narayanan, K. S.; Ianniello, R. M. PTC Int Appl WO 9919256 A2, 22 Apr 1999, 25 pp. (14) Antonietti, M.; Landfester, K. Ger Offen DE 19852784 A1, 18 May 2000. (15) Amselem, S.; Friedman, D. In Submicron emulsions in drug targeting and delivery; Benita, S., Ed.; Harwood Academic Publishers: New York, 1998; pp 153-173. (16) Nakajima, H.; Tomomasa, S.; Okabe, M. Preparation of Nanoemulsions; Proceedings of First Emulsion Conference; EDS: Paris, 1993; Vol. 1, pp 1-11/162. (17) Fo¨rster, T. In Surfactants in Cosmetics; Rieger, M., Rhein, L. D., Eds.; Marcel Dekker: New York, 1997; pp 105-125. (18) Katsumoto, Y.; Ushiki, H.; Mendibourne, B.; Graciaa, A.; Lachaise, J. J. Phys.: Condens. Matter 2000, 12, 3569-3583. (19) Esquena, J.; Solans, C. Prog. Colloid Polym. Sci. 1998, 110, 235239. (20) Forgiarini, A.; Esquena, J.; Gonza´lez, C.; Solans, C. Prog. Colloid Polym. Sci. 2000, 115, 36-39.
10.1021/la010808c CCC: $22.00 © 2002 American Chemical Society Published on Web 12/11/2001
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Langmuir, Vol. 18, No. 1, 2002 27
the phase inversion temperature (PIT) method introduced by Shinoda.22-24 Particular emphasis has been paid to the problem of Ostwald ripening that is commonly encountered within nano-emulsion systems.
The values of droplet size given in this report are those obtained by the REPES analysis. Stability was assessed by measuring the droplet size as a function of time.
Experimental Section
Results and Discussion
Materials. Decane, dodecane, tetradecane, and hexadecane were obtained from either Fluka or Merck. A branched C16 alkane, namely isohexadecane (commercial name Arlamol HD), was obtained from UNIQEMA (Belgium). Squalane (2,6,10,15,19,23-hexamethyltetracosane) was obtained from Sigma. All these oils were used as received. Technical grade polyoxyethylene lauryl ether with an average of 4 mol of ethylene oxide (EO) per surfactant molecule (Brij 30) was purchased from Sigma. In this h 4 (the bars are used to indicate that work it is abbreviated as C h 12E it is a technical grade surfactant). NaCl (purity > 99.5%) was obtained from Merck. Water was deionized and milli-Q filtered. Methods. HLB (Hydrophilic-Lipophilic Balance) Temperature Determination. Emulsions with an oil/water weight ratio in the region of 20/80 were prepared by simple shaking of the appropriate amounts of the oil, nonionic surfactant, and water containing 10-2 mol dm-3 NaCl at room temperature (∼25 °C). The conductivity of the resulting emulsions was measured as a function of temperature using a Crison 525 conductivity meter and a dipping cell (with Pt/platinized electrode) with a cell constant of 1.02 cm-1 (25 °C). The latter was determined using standard KCl solutions. Preparation of Nano-Emulsions. Emulsions were prepared, according to Shinoda,22-24 at a temperature near the PIT and then rapidly cooled to 25 °C by immersing the emulsion in an ice bath. The resulting systems were kept at 25 °C. Droplet Size and Stability Determinations. The mean droplet size and size distribution of the nano-emulsions were determined using photon correlation spectroscopy (PCS), also known as dynamic light scattering (DLS). A Malvern 4700 photon correlation spectrometer (Malvern Instruments, Malvern, U.K.) was used for this purpose. An argon laser (λ ) 488 nm) with variable intensity was used to cover the wide size range involved. Measurements were always carried out at a scattering angle of 90°. The scattering vector q is calculated from the equation25
HLB Temperature. Figure 1 shows the variation of conductivity with temperature for emulsions with 20 wt h 4 concen% hexadecane concentration and various C h 12E trations. At all surfactant concentrations, the conductivity
q ) (4πn/λ) sin(θ/2)
(1)
where n is the refractive index of the medium, λ is the wavelength, and θ is the scattering angle (90°). The droplet size is calculated using the Stokes-Einstein equation:
D ) kT/6πηR
(2)
where D is the diffusion coefficient, k is the Boltzmann constant, T is the absolute temperature, η is the viscosity of the continuous phase, and R is the hydrodynamic radius of the droplets (the core radius plus surfactant layer). The values of n and η were taken to be 1.332 and 0.89, respectively (for water at 25 °C). The DLS data were analyzed by (a) the standard program obtaining the Z average value, (b) the CONTIN26,27 method, and (c) a constrained regularization calculation algorithm known as REPES,28-30 incorporated in the analysis package GENDIST (interactive program for the analysis of homodyne DLS data). (21) Forgiarini, A.; Esquena, J.; Gonza´lez, C.; Solans, C. Prog. Colloid Polym. Sci., in press. (22) Shinoda, K.; Saito, H. J. Colloid Interface Sci. 1968, 26, 70. (23) Shinoda, K.; Saito, H. J. Colloid Interface Sci. 1969, 30, 258. (24) Shinoda, K.; Kunieda, H. In Encyclopedia of Emulsion Technology; Becher, P., Ed.; Marcel Dekker: New York, 1983; Vol. 1, pp 337367. (25) Cotton, J. P. In Neutron, X-Ray and Light Scattering: Introduction to an Investigative Tool for Colloidal and Polymeric Systems; Lindner, P., Zemb, Th., Eds.; North-Holland, Amsterdam, 1991; pp 3-18. (26) Provencher, S. W. Comput. Phys. Commun. 1982, 27, 213-217. (27) Provencher, S. W. Comput. Phys. Commun. 1982, 27, 229-241. (28) Jakes, J. Czech. J. Phys. 1988, B38, 1305-1316. (29) Nikolai, T.; Brown, W.; Johnsen, R. M.; Stepa´nek, P. Macromolecules 1990, 23, 1165-1174. (30) Johnsen, R. M. In Light Scattering in Biochemistry; Harding, S. E., Sttelle, D. B., Bloomfield, V. A., Eds.; The Royal Society of Chemistry: Cambridge, U.K., 1992; pp 77-91.
Figure 1. Conductivity as a function of temperature in the system aqueous 10-2 M NaCl/C h 12E h 4/hexadecane at different concentrations of surfactant, S, and constant oil concentration (20 wt %).
of the emulsion initially increases with the increase of temperature, reaching a maximum, and then it suddenly decreases. With surfactant concentrations of 3, 3.5, 4, and 5 wt %, there is a rapid reduction in conductivity with further increase of temperature. The HLB temperature or phase inversion temperature (PIT) was taken as the average value between the maximum and the minimum values of conductivity. With the 6, 7, and 8 wt % surfactant concentrations, the decrease in conductivity after reaching the maximum was not continuous and another welldefined maximum could be observed. In these cases, the PIT was also taken as the average between the highest and the lowest conductivity values (i.e. neglecting the intermediate well-defined maximum). The lack of continuity in the conductivity curves for the highest surfactant concentration may be attributed to the formation of liquid crystalline phases. As was described for a similar system,31 at such high surfactant concentration (above 5 wt %) the transition from O/W to W/O systems passes through the formation of LR (lamellar) and L3 phases. Table 1. Compositions and HLB Temperature of Samples in the System Aqueous NaCl 10-2 M/C h 12E h 4/Hexadecane at 20 wt % Oil Concentration wt % C h 12E h4
oil/water ratio
THLB (°C)
3.0 3.5 4.0 5.0 6.0 7.0 8.0
20.6/79.4 20.7/79.3 20.8/79.2 21.1/78.9 21.3/78.7 21.5/78.5 21.7/78.3
57 54 49 47 46 41 41
Table 1 gives a summary of the PIT or HLB temperatures as a function of surfactant concentration. There seems to be a gradual reduction of the HLB temperature h 4 concentration. This reduction with the increase in C h 12E may be attributed to the polydispersity of the commercial (31) Kunieda, H.; Fukuhi, Y.; Uchiyama, H.; Solans, C. Langmuir 1996, 12, 2136.
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Izquierdo et al.
surfactant (in this case, there is a wide distribution of alkyl chain length and EO units in the molecule). The chains with the lower EO content will preferentially partition to the oil phase. With an increase in surfactant concentration, there will be more accumulation of chains with low EO content in the oil phase, and this will result in a reduction of the HLB temperature. Alternatively, we may visualize that a surfactant layer consisting of chains with various EO contents will modify its properties in such a way that an effect on the HLB temperature is h 4 concenobserved. In other words, with the highest C h 12E trations, there will more accumulation of molecules with shorter EO chains at the interface, when compared with h 4 concentrations. the case for lower C h 12E h 4/ Stability of Nano-Emulsions of the Water/C h 12E Hexadecane System Prepared by the PIT Method h 4 Concentrations. As mentioned in the at Various C h 12E Experimental Section, the nano-emulsions were prepared by rapid cooling from a temperature near the PIT to 25 °C. The two most probable breakdown processes in these systems must be coalescence and Ostwald ripening. If coalescence was the driving force for instability, then the change of droplet size with time may follow the following equation:32
1/r2 ) 1/r02 - 8π/3ωt
where C(r) is the solubility of oil contained within a drop of radius r, C(∞) is the bulk phase solubility (the solubility of an infinity large droplet), Vm is the molar volume of the oil, R is the gas constant, and T is the absolute temperature. For two droplets with radii r1 and r2, the difference in Laplace pressure is as follows:
(RT/Vm) ln[C(r1)/C(r2)] ) 2γ[1/r1 - 1/r2]
(5)
The Lifshitz-Slezov and Wagner (LSW) theory34-36 gives an expression for the Ostwald ripening rate:
ω ) dr3/dt ) 8/9[(C∞γVmD)/FRT)]
(6)
where F is the density of the oil and D is the diffusion in the continuous phase.
(3)
where r is the average droplet radius after time t, r0 is the value at t ) 0, and ω is the frequency of rupture per unit of surface of the film. Although the above equation has been developed for concentrated systems, we have used it in our nanoemulsion systems to show whether coalescence was the driving force for instability.
Figure 3. Nano-emulsion r3 as a function of time at 25 °C in the system water/C h 12E h 4/hexadecane at different concentrations of surfactant, S, and constant oil concentration (20 wt %). Table 2. Compositions, Initial Droplet Radius, and Ostwald Ripening Rates, ω, at 25 °C, of Nano-Emulsions in the System Water/C h 12E h 4/Hexadecane at 20 wt % Oil Concentration
Figure 2. Nano-emulsion r-2 as a function of time at 25 °C in the system water/C h 12E h 4/hexadecane at different concentrations of surfactant, S, and constant oil concentration (20 wt %).
As an illustration, Figure 2 shows plots of 1/r2 versus t for hexadecane/water nano-emulsions at various C h 12E h4 concentrations. In all cases, the plots did not follow the predictions of eq 3, indicating that coalescence, as described by the model of ref 32, may not be the mechanism of instability. An alternative mechanism for instability of nanoemulsions would be Ostwald ripening. The latter process arises from the difference in solubility between small and large droplets due to the different Laplace pressures, p. Inside a droplet p is equal to 2γ/r, where γ is the interfacial tension and r is the droplet radius. As described by Kelvin,33 the solubility as a function of the droplet size is given by the following expression:
C(r) ) C(∞) exp(2γVm/rRT)
(4)
wt % C h 12E h4
oil/water ratio
r (nm)
ω (× 1027 m3 s-1)
4.0 5.0 6.0 7.0 8.0
20.8/79.2 21.1/78.9 21.3/78.7 21.5/78.5 21.7/78.3
66 47 34 30 26
2.3 4.1 10.2 18.0 39.7
Equation 6 predicts a linear relationship between r3 and t. As an illustration, Figure 3 shows several plots for various C h 12E h 4 concentrations for the same nano-emulsions described above. These linear plots mean that the main driving force for instability is Ostwald ripening. The Ostwald ripening rate, ω, can be calculated from the slope of the linear plot. Table 2 gives a summary of the initial droplet radii and the Ostwald ripening rate constants at h 4 concentrations. The droplet radius decreases various C h 12E with the increase in surfactant concentration because of the increase in interfacial area and the decrease in interfacial tension, γ. As is well-known, γ reaches a minimum value at the HLB temperature.37,38 Therefore, the compositions with HLB temperatures closer to 25 °C (32) Deminie`re, B. In Modern Aspects of Emulsion Science; Binks, B. P., Ed.; The Royal Society of Chemistry: Cambridge, U.K., 1998; pp 261-291. (33) Hunter, R. J. Foundations of Colloid Science; Oxford University Press Inc.: New York, 1993. (34) Lifshitz, I. M.; Slezov, V. V. J. Phys. Chem. Solids 1961, 19, 35. (35) Wagner, C. Z. Elektrochem. 1961, 65, 581. (36) Kabalnov, A. S.; Shchuckin, E. D. Adv. Colloid Interface Sci. 1992, 38, 69.
Formation and Stability of Nano-Emulsions
Langmuir, Vol. 18, No. 1, 2002 29
(those with higher surfactant concentrations as shown in Table 1) are those having lower interfacial tensions and smaller droplet sizes. Concerning Ostwald ripening rates, it is clear from Figure 3 and Table 2 that ω increases with the increase in surfactant concentration (from 2.3 × 10-27 to 39.7 × 10-27 m3 s-1). These values are 2 orders of magnitude higher than the theoretical value, 2.1 × 10-29 m3 s-1, calculated according to the LSW theory34-36 taking into account the molecular solubility of the hydrocarbon during the process, C(∞) ) 0.3 × 10-10 mL mL-1, using a correction coefficient39 for the volume fraction, φ ) 0.2, equal to 2, and assuming that the diffusion coefficient D is 0.8 × 10-9 m2 s-1 and that γ is equal to γcmc ) 5 mN m-1. The LSW theory assumes that the mass transport is due to molecular diffusion through the continuous phase and that there is no interaction between the particles, which are spherical. Consequently, the theory applies to low dispersed phase volume fractions. The difference between theoretical and experimental rates could be due to factors not taken into account in the LSW theory, such as oil transport due to the presence of surfactant aggregates in the continuous phase, that is, micelles,40,41 and Brownian motion of the droplets.42 The increase of ω with the increase in surfactant concentration can be due to a number of effects. First, by increasing the surfactant concentration, the droplet size decreases, as shown in Table 2, favoring the Brownian motion and increasing ω. Second, the number of micelles is expected to increase with the increase in surfactant concentration41 and this results in an increase in the flux, J, of oil molecules, as given by Fick’s first law,43
J ) -D(∂C/∂x)
(7)
where D is the molecular diffusion coefficient of the oil and (∂C/∂x) is the concentration gradient. Although diffusion of micelles is slower than diffusion of molecules (usually D decreases by a factor of ∼10, the volume of a micelle is ∼1000 times higher than that of the hydrocarbon molecule, and the radius is ∼10 times higher than that of the hydrocarbon molecule), (∂C/∂x) can increase by several orders of magnitude as a result of solubilization.44 Then, the overall effect would be an increase in J and hence an increase in Ostwald ripening rate. The third reason for the increase of Ostwald ripening rate, ω, with the increase in surfactant concentration could be due to partitioning of surfactant molecules between the oil and the aqueous phases. As discussed above, with higher surfactant concentration, accumulation of the molecules with the shorter EO chains at the interface will take place.24,38 It is likely that accumulation of low HLB molecules results in lowering of the Gibbs elasticity (interfacial gradients are dampened), and these may result in an increase of the Ostwald ripening rate. In addition, the presence of different surfactant aggregates, as the surfactant concentration increases, would also influence Gibbs elasticity. The presence of surfactant aggregates with a lamellar liquid crystalline structure in nanoemulsions of a similar system has been reported recently.5 Moreover, our results of conductivity as a function of temperature (Figure 1) showed a peak at higher surfactant concentrations due to surfactant aggregates other than micelles. Unfortunately, at present we are unable to isolate the relative importance of each effect and it is likely that all effects described above operate simultaneously. Influence of Solubility of the Oil Phase. As predicted by the LSW theory, eq 6, the increase in oil solubility
should enhance the rate of Ostwald ripening. This is illustrated in Figure 4, which shows plots of r3 versus t for a series of linear alkanes (C10 to C16) and also for isohexadecane. It is clear that when oil solubility increases, the slope of the line (i.e. the rate of Ostwald ripening) increases.
Figure 4. Nano-emulsion r3 as a function of time at 25 °C in the system water/C h 12E h 4/aliphatic hydrocarbon for various alkanes at constant oil concentration (20 wt %) and surfactant concentration (4 wt %). Table 3. Compositions, HLB Temperatures, Molecular Solubility of Hydrocarbons in Water, C(∞), and Ostwald Ripening Rates, ω, at 25 °C of nano-emulsions in the System Water/C h 12E h 4/Aliphatic Hydrocarbon at 20 wt % Oil and 4.0 wt % Surfactant Concentration oil
THLB (°C)
C(∞) (× 1010 mL mL-1)
r (nm)
ω (× 1027 m3s-1)
decane dodecane tetradecane hexadecane isohexadecane
38.5 45.5 49.5 49.8 43.0
710.0 52.0 3.7 0.3
59 62 64 66 60
20.9 9.3 4.0 2.3 8.0
Table 3 shows HLB temperatures, nano-emulsion initial droplet radius, and ω obtained for various alkanes as well as the molecular solubility in water.45 The HLB temperature decreases with the decrease in hydrocarbon alkyl chain length. As mentioned above, since the experiments are carried out at 25 °C, the system with the HLB temperature closer to 25 °C will achieve lower interfacial tension values. As can be observed in Table 3, the initial droplet radius decreases with the decrease in HLB temperature, which can be attributed to a decrease in the interfacial tension. Table 3 also shows that the Ostwald ripening rate increases with the increase of alkane solubility in water. There is no linear relationship between these two parameters, because Ostwald ripening rate does not depend only on oil solubility but also on interfacial tension and diffusion. It is interesting to note that the rate of Ostwald ripening for isohexadecane is close to that (37) Kunieda, H.; Friberg, S. Bull. Chem. Soc. Jpn. 1981, 54 (4), 1010-1014. (38) Bourrel, M.; Schechter, R. S. Microemulsion and Related System; Surfactant Science Series; Marcel Dekker: New York, 1988; p 30. (39) Enamoto, Y.; Kawasaki, K.; Tokuyama, M. Acta Metall. 1987, 35, 907. (40) Kabalnov, A. S. Langmuir 1994, 10, 680. (41) Taylor, P. Colloids Surf., A: Physicochem. Eng. Aspects 1995, 99, 175-185. (42) Kabalnov, A. S.; Makarov, K. N.; Pertzov, A. V.; Shchukin, E. D. J. Colloid Interface Sci. 1990, 138 (1), 98-104. (43) Hiemenz, P. C. Principles of Colloid and Surface Chemistry; Lagowski, J. J., Ed.; Marcel Dekker: New York, Basel, 1977. (44) Lee, G. W. J.; Tadros, Th. F. Colloids Surf. 1982, 5, 117-127. (45) McAuliffe, C. J. Phys. Chem. 1966, 70, 1267-1275.
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of n-dodecane, which may imply that the properties of these two hydrocarbons are similar. Influence of Addition of a Less Soluble Oil (Squalane) on the Ostwald Ripening Rate. Higuchi and Misra46 were the first to propose the addition of a second, less soluble, component to the dispersed phase to reduce the Ostwald ripening rate.47,48 Accordingly, squalane was added to the system with isohexadecane, in order to enhance nano-emulsion stability. Figure 5 shows plots of
Izquierdo et al.
The rates of Ostwald ripening for these two systems are 8.2 × 10-27 and 5.5 × 10-27 m3 s-1, respectively. As expected, the addition of squalane causes a reduction in the rate of Ostwald ripening. This reduction is attributed to the partition of squalane in the isohexadecane droplets, which becomes different for different sized droplets. During Ostwald ripening, equilibrium is established when the difference in chemical potential between different size droplets (which results from curvature effects) is balanced by the difference in chemical potential resulting from partition of the two components.1,46 This explains the reduction in Ostwald ripening rate on addition of squalane. Conclusions Nano-emulsions with a droplet size in the range 50h 4/ 130 nm have been obtained in the system water/C h 12E hexadecane by the PIT emulsification method at 20 wt % oil concentration and at a surfactant concentration higher than 3.5 wt %. Investigations of the nano-emulsions showed that the stability decreases with the increase in surfactant concentration up to 8.0 wt %. The stability of the nano-emulsions also decreased with the increase in oil solubility due to the increase of Ostwald ripening rate as a consequence of an increase in the oil diffusion rate.
Figure 5. Nano-emulsion r3 as a function of time at 25 °C in the system water/C h 12E h 4/isohexadecane/squalane for two isohexadecane/squalane weight ratios at constant O/W weight ratio (20/80) and surfactant concentration (4 wt %).
r3 versus t for isohexadecane and a 90/10 weight ratio of isohexadecane/squalene.
Acknowledgment. Financial support by UNIQEMA is gratefully acknowledged. The authors also acknowledge the support by “Comissionat per a Universitats i Recerca, Generalitat de Catalunya” (Grant 1999SGR-00193). LA010808C (46) Higuchi, W. I.; Misra, J. J. Pharm. Sci. 1962, 51, 459. (47) Kabalnov, A. S.; Pertsov, A. V.; Shchukin, E. D. Colloids Surf. 1987, 24, 19. (48) Weers, J. G.; Arlaukas, R. A. Langmuir 1995, 11, 474.
