Kinetics of Oil Exchange in Nanoemulsions Prepared with the Phase

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Kinetics of Oil Exchange in Nanoemulsions Prepared with the Phase Inversion Concentration Method Ingo Hoffmann,†,§ Miriam Simon,† Anja Hörmann,† Thorsten Gravert,† Peggy Heunemann,†,§ Sarah E. Rogers,‡ and Michael Gradzielski*,† †

Stranski-Laboratorium für Physikalische und Theoretische Chemie, Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 124, Sekr. TC 7, D-10623, Berlin, Germany ‡ ISIS, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX, U.K. § Institut Max von Laue-Paul Langevin (ILL), F-38042 Grenoble Cedex 9, France S Supporting Information *

ABSTRACT: Nanoemulsions (NEs) are metastable emulsions with droplet sizes between 20 and 100 nm and with a wide range of applications, for example, in polymerization, in pharmaceutical and cosmetic formulations, and as drug delivery systems. Even though they are not in thermodynamic equilibrium, they can be metastable over relatively long times and have the advantage that they can be formed easily by low energy input methods. In particular, the phase inversion concentration (PIC) method allows the formation of NEs by the dilution of a suitable mixture of oil and surfactants with water. In this paper, we investigate the kinetics of the oil exchange process of NEs formed by the PIC method by looking at the exchange of different hydrophobic oils and by employing contrast variation stopped flow small-angle neutron scattering. These experiments demonstrate that this exchange becomes substantially slower by increasing the chain length of the alkane. This indicates a mechanism where monomer exchange is relevant, which would indicate also that for aging one would expect Ostwald ripening to be the determining factor. Such investigations can be carried out in a unique fashion by means of neutron scattering, and the results have important implications for the optimization of NE formulations.

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INTRODUCTION As opposed to microemulsions, nanoemulsions (NEs) are not thermodynamically stable but can be metastable for relatively long times, from many days to months.1 Typically, NE droplets are in the size range of 20−100 nm,2 which is larger than microemulsions that have a typical size range of 5−20 nm.3 Accordingly NEs have the advantage of requiring less surfactant to emulsify a given amount of oil. As opposed to emulsions, they can be formed by low energy input methods such as the phase inversion temperature4−6 or the phase inversion concentration (PIC)2,7,8 method, which is used in this paper and involves the dilution of an oil−surfactant mixture with water. These formation methods are very interesting, but such spontaneous emulsification is still far from being fully understood.9 The applications of NEs range widely from polymerization,10,11 where they serve as a reaction media, through cosmetics and pharmaceutics, to drug delivery systems.12,13 In general, it might be noted that self-assembled systems are highly dynamic,14−16 an aspect that is often overlooked during their evaluation. In this respect, individual microemulsions are highly dynamic systems, and their droplets have a relatively © XXXX American Chemical Society

short life span since they are constantly destroyed and rebuilt, with characteristic exchange times of 10 μs to 1 ms.17 For instance, the interdroplet exchange in nonionic W/O microemulsion droplets of C12E5/heptane occurs on the timescale of some milliseconds.18 The aggregation kinetics of O/W microemulsion droplets of the C12E5/tetradecane system was studied by means of the iodine laser temperature-jump method19 and found to take place in the millisecond-range with an activation energy of several kT, which decreases with increasing droplet size.20 The activation energy for such exchange processes increases with increasing chain length of the surfactant (while thickening the amphiphilic monolayer) and thereby increases the bending elasticity of the amphiphilic monolayer; this also correlates with the emulsion stability in the two-phase region of the phase diagrams.21 By contrast, NE droplets are supposed to be stable for much longer times, and in the case of W/O NEs, it has been observed that the exchange between droplets only takes place over timescales of minutes or Received: August 11, 2016 Revised: October 21, 2016 Published: October 24, 2016 A

DOI: 10.1021/acs.langmuir.6b03009 Langmuir XXXX, XXX, XXX−XXX

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this applies strictly for the scattering angle going to zero and there will be a finite scattering contribution because of the natural polydispersity in composition of the mixed hydrogenated/deuterated oils). We used the stopped flow technique coupled to small-angle scattering25−27 to guarantee efficient mixing and to have a sufficiently high time resolution and range, as little a priori knowledge concerning the relevant timescales is available. Knowing the exchange mechanism of the oil components not only is of fundamental scientific interest but also allows the more rational design of NE formulations as they can be optimized to suppress the relevant mechanism, either by stabilizing the surfactant shell or by reducing the solubility of the oil component.

hours but then can be initiated by application of ultrasonication.22 In general, aging of the NE droplets occurs because of either coalescence (two droplets collide and form a new droplet) or Ostwald ripening, where individual molecules are exchanged between existing aggregates. While the coalescence process depends on the droplet concentration and their stability (i.e., the robustness of the amphiphilic film and the interparticle interactions), the Ostwald ripening is limited to the diffusion of the exchanging molecules through the solvent and hence is impacted by the hydrophobicity of the oil. Here, the timescales of the exchange should be significantly slower for longer chain oils. Ostwald ripening is commonly assumed to be one of the most serious instability problems of NEs and therefore has been investigated for quite some time.23,24 But so far, only very little information exists concerning the simple exchange of oils between droplets without changing the average droplet size. This exchange could be based on diffusing molecules that would ultimately lead to Ostwald ripening but could also be based on a coalescence mechanism. Accordingly so far, little is known about the timescale and the mechanism of this exchange process, and this information would be difficult if not impossible to gain by any other method than neutron scattering (which relies on isotopic labeling, which has hardly any impact on the colloidal behavior of the components). To address this question of how oil exchange occurs in NEs, we performed small-angle neutron scattering (SANS) experiments where we used a stopped flow (sf) apparatus to mix two otherwise identical NEs, where one of them contained a deuterated oil whereas the other contained a hydrogenated oil. The solvent was a mixture of H2O and D2O, which would match the average contrast of the droplets after the full exchange of the oil (see Figure 1). In other words, both starting components are visible, and as they exchange their oil components they turn invisible during the experiment (where

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MATERIALS AND METHODS

Materials. The NEs investigated in this study were prepared by the PIC method. The oil/surfactant mixture used for this process consisted of Tego Care P4L (polyglycerol-4 laurate; Evonik Goldschmidt AG) and Rewopol SB FA 30 (disodium laureth sulfosuccinate; Evonik Goldschmidt AG) as surfactants and Euxyl K300 (Schülke and Mayr GmbH) as a cosurfactant, which is a mixture of phenoxyethanol, methylparaben, butylparaben, ethylparaben, propylparaben, and isobutylparaben (which in practical applications is used as a liquid cosmetic preservative). As oils, Tegosoft DEHC (diethylhexyl carbonate; Evonik Goldschmidt AG), different alkanes (octane, decane, dodecane, tetradecane, and hexadecane), and both hydrogenated and deuterated oils (Fluka Chemicals: octane, decane, dodecane, and hexadecane; Sigma Aldrich: tetradecane, Euriso top: Doctane, D-decane, D-dodecane, CDN Isotopes: D-tetradecane, and Dhexadecane) were employed. A summary of the compounds used can be found in Table S1. The composition of the oil/surfactant mixture was 12 wt % Euxyl K300, 21.12 wt % P4L, 0.88 wt % Rewopol SB FA 30, and 66 wt % oil, which is a mixture of alkane and DEHC. The mixture was prepared with hydrogenated oils and with deuterated ones, taking into account the density difference to maintain a constant molecular ratio. For the kinetic experiments, the oil/surfactant mixtures were diluted with water (solvent) to concentrations of 0.2, 0.5, 1, 2, and 5 wt % at least a day before mixing them in the stopped flow apparatus. The reference samples with both hydrogenated and deuterated oils were prepared at the same time as the NEs with only hydrogenated or deuterated oil. NEs with short chain alkanes tend to cream (see Figure S1) but can be easily redispersed by gentle shaking without influencing the NE. UV/Vis measurements showed that a long-time metastable state is reached after a few hours (see Figure S2). Methods. SANS was carried out on the Sans2d small-angle diffractometer at the ISIS Pulsed Neutron Source (STFC Rutherford Appleton Laboratory, Didcot, U.K.).28,29 A simultaneous Q-range of 0.045−7 nm−1 was achieved utilizing an incident wavelength range of 1.75−16.5 Å and employing a sample to detector distance of 4 m, with the 1 m2 detector offset vertically 60 mm and sideways 100 mm. Each raw scattering data set was corrected for the detector efficiencies, sample transmission, and background scattering from the empty cell and converted to absolute scale with a standard sample (a solid blend of hydrogenous and perdeuterated polystyrene) using the software Mantid.30 A stopped flow apparatus (BioLogic SFM-400) was employed to mix otherwise identical NEs with hydrogenated and deuterated oils. The flow rate was fixed at 2 mL/s. The mixing volume was 650 μL. The kinetics were recorded for 2−5 h. To normalize the change of scattering intensity over time, spectra of the individual solutions and their 1:1 mixtures were recorded. The reduced intensities i(t) are given by

Figure 1. Two otherwise identical NEs with deuterated or hydrogenated oil are mixed in the stopped flow apparatus. With time they exchange the oil. The solvent is chosen so that it matches the average contrast of the NEs with 50% hydrogenated oil and 50% deuterated oil.

i(t ) = (I(t ) − Ifinal)/(I(0) − Ifinal)

(1)

where Ifinal is the intensity from the samples prepared 30 h before the measurement (and assuming this to be the final state), I(0) is the B


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Figure 2. Phase behavior of oil surfactant mixtures where the fraction of oil in the mixture was fixed at 66 wt % and the ratio of DEHC/alkane was varied. weighted average of the individual solutions I(0) = 0.5Ihydrogenated + 0.5Ideuterated, and the intensities were calculated as the average intensity between Q = 0.05 and 0.075 nm−1. The coherent intensity in a SANS experiment depends on the difference in scattering length density between the matrix and the dispersed phase, which depends on the isotopic composition. The scattering lengths of deuterium and hydrogen are drastically different. Therefore, good contrasts can be achieved by deuterating some of the components, and the contrast of water can easily be tuned by replacing H2O by a mixture of H2O and D2O. When mixing NE droplets with hydrogenated and deuterated oils in a solvent that has the scattering length density of the averaged NE, for homogeneous particles the initial intensity reads

d[X] = kXin − kXout[X] dt

where [X] is the fraction of either hydrogenated oil [H] or deuterated oil [D] in the droplet, so that [H] + [D] = 1. Solving the differential equation leads to

[X](t ) =

(2)

where Q is the magnitude of the scattering vector 4π/λ sin(θ/2) with neutron wavelength λ and scattering angle θ, 1N is the total particle number density of the droplets, V is the volume of the droplets, and P(Q) is the form factor of the droplets, which is a constant here, as the structure of the droplets does not change. SLDdeuterated and SLDhydrogenated are the scattering length densities of the NEs with deuterated and hydrogenated oils, whereas SLDav is the H2O/D2O mixture that corresponds to the average scattering length density. After the exchange of the oil is completed, the final intensity reads

I(Q ) = 1N ((SLDfinal − SLDav )2 )V 2P(Q )

kXin + c exp( − kXoutt ) kXout

(5)

We assumed that the monomeric oil concentration in the aqueous phase is constant, and therefore kXin, the rate constant for the uptake of [X] from the continuous phase, is a pseudo-zero-order rate constant, whereas kXout, the rate constant for the loss of [X] to the continuous phase, is a first-order rate constant. Also, as the two species are chemically identical, we can reasonably approximate kHin = kDin and kHout = kDout and drop the index D or H. As the overall size of the droplets is assumed to be constant and the observable part of the oil mixture consists of either hydrogenated or deuterated oil, the concentration of one can be expressed as a function of the other, so that

I(Q ) = 1N (0.5(SLDdeuterated − SLDav )2 + 0.5(SLDhydrogenated − SLDav )2 )V 2P(Q )

(4)

[D](t ) = 1 − [H](t ) = 1 −

k in − c exp(− koutt ) kout

(6)

Assuming that we start with a droplet with only hydrogenated oil

[H](0) = 1 =

(3)

k in +c kout

(7)

so that c = 1 − kin/kout. If we neglect changes in the shape of the droplets, the coherent intensity measured by SANS from a droplet is proportional to the squared deviation from the bulk concentration, and the overall signal is proportional to the sum over all droplets

where SLDfinal is the scattering length density of the droplets after exchange. When mixing equal amounts of droplets with hydrogenated and deuterated oils SLDfinal = 0.5SLDhydrogenated + 0.5SLDdeuterated, we chose the composition of our solvent so that SLDfinal = SLDav. Therefore, the intensity (almost) vanishes at the end of the exchange process (except for not perfect matching, remaining scattering due to the internal structure of the NEs, and the statistical fluctuations of the SLD of the NEs with the mixed oils). Theory. If the oil exchange between NE droplets takes place via individual oil molecules dispersed in the aqueous phase and if we assume that the droplets are stable on the timescale of the experiment (i.e., the overall amount of oil in a droplet is constant), the change in the amount of either deuterated or hydrogenated oil over time in a droplet is given by

I(t ) ∝ x(t ) =

∑ ([X i(t )] − [X eq])2 ∑ ([X i(0)] − [X eq])2

(8)

where [Xeq] is the equilibrium concentration of component X. This quantity is identical for deuterated or hydrogenated oil. We can expect an exponential form for the decay of the intensity if the exchange of oils takes place via diffusion of individual oil molecules through the bulk phase, and polydispersity of the droplets will result in some deviations from the ideal exponential form. C


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Langmuir Deriving an analytical expression for the kinetics of coalescence is less trivial; however, a simple simulation, where a given number of randomly chosen droplet exchanges its oil with another randomly chosen droplet, so that two droplets with the average oil composition are created in every time step, shows an exponential decay of x (see Figure S3). Therefore, it is impossible to discern between the two mechanisms based on the shape of the intensity decay, but they should be distinctly different with respect to their scaling, the type of oil, and droplet concentration. Although oils with a longer chain and with a lower solubility in the aqueous phase will greatly slow down the exchange through monomers (Ostwald ripening), an increase in the droplet concentration should speed up the coalescence-based mechanism, as collisions between droplets become more frequent.

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RESULTS AND DISCUSSION Phase Diagram. Similar NE systems had been studied in our group previously.8,31 However, the oil used was DEHC. As deuterated alkanes are commercially available with variable alkyl chain lengths, we investigated the possibility of substituting as large of a fraction of DEHC as possible with alkanes to maximize the effect observable by SANS. Not all DEHC/alkane mixtures form stable oil/surfactant mixtures; therefore, we studied the phase diagram of the system with a fixed amount of oil (66 wt %) but by varying the DEHC/alkane ratio (see Figure 2). It can be seen that solutions with a DEHC/alkane ratio of 50:50 are stable for most alkanes, except for hexadecane, and in general, the solubilization capacity is lower for longer chain oils, as previously observed for microemulsions.32,33 Therefore, we chose to study NEs with that DEHC/alkane ratio, except for hexadecane where a ratio of 60:40 was used. SF-SANS. To measure the exchange kinetics, we prepared NEs with hydrogenated and deuterated alkanes separately in an H2O/D2O mixture that corresponds to the average contrast of the mixed solutions. The ratio was calculated to be 70 vol % H2O and 30 vol % D2O for all alkanes except for hexadecane where a ratio of 73:27 vol % H2O:D2O had to be used. The two NEs of an alkane with a given chain length, a given concentration, and different contrast were mixed in the stopped flow cell, and the exchange of the hydrogenated and the deuterated alkane chains was followed by the decrease in scattering intensity over time. First, we tested the effect of the chain length of the different alkanes on the exchange kinetics. We prepared solutions with 2 wt % of oil/surfactant mixtures with the different alkanes and mixed them in the stopped flow cell. For short chains (C8,C10), the SANS spectra show a decay with a slope of Q−2 and no discernable features, which is in agreement with a relatively broad distribution of droplet sizes (see Figure S4). Longer chains (C12,C14,C16) show a shoulder at about 0.2 nm−1 (see Figure 3). Its relative weight increases with the chain length. The shoulder can be attributed to the presence of smaller microemulsion droplets with a size of about 10 nm. Such a bimodality in the droplet size distribution was observed previously in similar systems8,31 containing pure DEHC. The shape does not change during the kinetic measurements. In the measurement of the final state after about 30 h, the weight of the shoulder is somewhat decreased. After mixing the two NEs, the intensity of the scattering curve decreases with no noticeable change in the shape of the curve. The observed decay of intensity with time is exponential (see Figure 4) and therefore can be described as i(t ) = a exp( −t /τ )

Figure 3. SANS curves of 2 wt % tetradecane oil surfactant mixture after the times indicated in the legend. The curve for 0 s is the average of the measurements with only hydrogenated and only deuterated oils (see eq 2). The intensity decays with no change in shape on the timescale of the kinetic measurement. However, the relative weight of the shoulder is somewhat decreased after more than 1 day.

Figure 4. Reduced intensity over time for different oils. The decay is exponential, as can be seen from the good agreement with the fits.

where the factor a accounts for small deviations from 1 in the normalization and τ is the relaxation time. This suggests that the exchange is dominated by only a single mechanism. The process is relatively slow, on the order of a few hours (see Figures 5 and 7). Furthermore, it can be seen that the decay gets significantly slower as the chain length of the alkane increases (see Figure 5). The curves for octane and decane were not recorded for a longer time, as the NE starts creaming. However, a gentle agitation could redisperse the NE droplets, so that it was possible to record the final state after 30 h. For hexadecane, no significant change can be observed within the timescale of the measurement (see Figure S5). This result of a clear dependence of the exchange rate on the length of the alkane suggests that the exchange of oil between droplets may be related to the diffusion of monomeric oil molecules through the aqueous phase. However, it should be noted that the dependence of the kinetic rate on the length of the alkanes is much less pronounced than the dependence of alkane solubility in water,34 which indicates that the reduction

(9) D


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increasing concentration (see Figure 7), which implies that the mechanism by which the exchange happens is Ostwald ripening

Figure 5. Relaxation time τ vs chain length of the alkane. As the chain length is increased, the relaxation time increases considerably. The exchange in hexadecane was too slow to be covered in this experiment. Figure 7. Relaxation time τ vs concentration of the oil surfactant mixture with dodecane. As the concentration is increased, τ becomes slower rather than faster, as would be expected for a coalescence-based exchange mechanism.

of the oil exchange rate for increasing chain length cannot be exclusively linked to the lower water solubility. Furthermore, these results correspond to the macroscopic stability of the NEs. Phase separation was observed to occur after some hours for the NEs with shorter chain oils, whereas NEs prepared with tetra- or hexadecane are stable for days (see Figure S1). In conclusion, we can say that the faster the exchange of single oil molecules via diffusion through the solvent, the more Ostwald ripening of the droplets can take place, which leads to bigger droplets and therefore creaming of the sample. We also investigated the exchange kinetics of NEs with dodecane as an alkane component at different concentrations and prepared hydrogenated and deuterated samples at 0.2, 0.5, 1, 2, and 5 wt %. If the oil exchange took place through collisions of droplets, the decay of intensity should become faster with increasing droplet concentration. The decay of intensity takes an exponential form at all concentrations investigated (see Figure 6), and the observed decay times seem to become slower rather than faster with

at all concentrations and coalescence does not play a major role in the oil exchange. The unexpected slowing down might be due to changes in the size distribution of the droplets and a different interfacial composition, as with increasing dilution less cosurfactant will be in the amphiphilic monolayer, which thereby becomes stiffer. Combining our findings that the observed decay in the intensity with time is exponential and that the decay time depends strongly on the hydrophobicity of the oil but not on the NE concentration, we can say that the exchange of oil in these NE droplets happens almost exclusively via an exchange of individual oil molecules. The diffusion of the individual oil molecules should scale directly with their respective solubility in water. Most studies available suggest that the solubility of n-alkanes decreases with increasing chain length up to dodecane, where it reaches a plateau. But with the help of molecular dynamics simulations, it was found that the solubility actually decreases further, following an (nearly) exponential decay,35 which corresponds to our findings very well.

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DISCUSSION In this article, we investigate the kinetics of the exchange of oil in oil-in-water (O/W) NE droplets with the aid of SF-SANS, where these NE droplets are formed by the PIC mechanism.8 These are the first measurements where the exchange rate of a single type of oil molecules in a NE was observed directly. This was possible due to the ability of neutron scattering to differentiate between different isotopes, and we made the oil exchange visible by employing NEs containing hydrogenated or deuterated oil in the mixing process. The dynamics of NEs is an interesting question for applications (for instance for delivery of active agents) but also with respect to their high kinetic (colloidal) stability, which is still not fully comprehended.1,23,36−38 With the aim of shedding light on this question, we employed NEs in which we varied systematically the chain length of straight chain alkanes to gain insights into

Figure 6. Reduced intensity vs time for different concentrations of the oil/surfactant mixture with dodecane. The decay is exponential, as can be seen from the good agreement with the fits. E


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(4) Shinoda, K.; Saito, H. The effect of temperature on the phase equilibria and the types of dispersions of the ternary system composed of water, cyclohexane, and nonionic surfactant. J. Colloid Interface Sci. 1968, 26, 70−74. (5) Fö rster, T.; von Rybinski, W.; Wadle, A. Influence of microemulsion phases on the preparation of fine-disperse emulsions. Adv. Colloid Interface Sci. 1995, 58, 119−149. (6) Izquierdo, P.; Feng, J.; Esquena, J.; Tadros, T. F.; Dederen, J. C.; Garcia, M. J.; Azemar, N.; Solans, C. The influence of surfactant mixing ratio on nano-emulsion formation by the pit method. J. Colloid Interface Sci. 2005, 285, 388−394. (7) Maestro, A.; Solè, I.; González, C.; Solans, C.; Gutiérrez, J. M. Influence of the phase behavior on the properties of ionic nanoemulsions prepared by the phase inversion composition method. J. Colloid Interface Sci. 2008, 327, 433−439. (8) Heunemann, P.; Prévost, S.; Grillo, I.; Marino, C. M.; Meyer, J.; Gradzielski, M. Formation and structure of slightly anionically charged nanoemulsions obtained by the phase inversion concentration (PIC) method. Soft Matter 2011, 7, 5697−5710. (9) Solans, C.; Morales, D.; Homs, M. Spontaneous emulsification. Curr. Opin. Colloid Interface Sci. 2016, 22, 88−93. (10) Antonietti, M.; Landfester, K. Polyreactions in miniemulsions. Prog. Polym. Sci. 2002, 27, 689−757. (11) El-Aasser, M. S.; Miller, C. M. In Polymeric Dispersions: Principles and Applications; Asua, J. M., Ed.; Springer Netherlands: Dordrecht, 1997; pp 109−126. (12) Tamilvanan, S. Oil-in-water lipid emulsions: Implications for parenteral and ocular delivering systems. Prog. Lipid Res. 2004, 43, 489−533. (13) Bivas-Benita, M.; Oudshoorn, M.; Romeijn, S.; van Meijgaarden, K.; Koerten, H.; van der Meulen, H.; Lambert, G.; Ottenhoff, T.; Benita, S.; Junginger, H.; Borchard, G. Cationic submicron emulsions for pulmonary DNA immunization. J. Controlled Release 2004, 100, 145−155. (14) Gradzielski, M. Kinetics of morphological changes in surfactant systems. Curr. Opin. Colloid Interface Sci. 2003, 8, 337−345. (15) Gradzielski, M. Investigations of the dynamics of morphological transitions in amphiphilic systems. Curr. Opin. Colloid Interface Sci. 2004, 9, 256−263. (16) Dynamics of Surfactant Self-Assemblies: Micelles, Microemulsions, Vesicles and Lyotropic Phases; Zana, R., Ed.; CRC Press, 2005; Vol. 125. (17) López-Quintela, M. A.; Tojo, C.; Blanco, M. C.; Rio, L. G.; Leis, J. R. Microemulsion dynamics and reactions in microemulsions. Curr. Opin. Colloid Interface Sci. 2004, 9, 264−278. (18) Clark, S.; Fletcher, P. D. I.; Ye, X. Interdroplet exchange rates of water-in-oil and oil-in-water microemulsion droplets stabilized by pentaoxyethylene monododecyl ethers. Langmuir 1990, 6, 1301−1309. (19) Holzwarth, J. F.; Schmidt, A.; Wolff, H.; Volk, R. Nanosecond temperature-jump technique with an iodine laser. J. Phys. Chem. 1977, 81, 2300−2301. (20) Fletcher, P. D. I.; Holzwarth, J. F. Aggregation kinetics of oil-inwater microemulsion droplets stabilized by C12E5. J. Phys. Chem. 1991, 95, 2550−2555. (21) Fletcher, P. D. I.; Horsup, D. I. Droplet dynamics in water-in-oil microemulsions and macroemulsions stabilised by non-ionic surfactants. correlation of measured rates with monolayer bending elasticity. J. Chem. Soc., Faraday Trans. 1992, 88, 855−864. (22) Landfester, K. Synthesis of colloidal particles in miniemulsions. Annu. Rev. Mater. Res. 2006, 36, 231−279. (23) Wooster, T. J.; Golding, M.; Sanguansri, P. Impact of Oil Type on Nanoemulsion Formation and Ostwald Ripening Stability. Langmuir 2008, 24, 12758−12765. (24) Taylor, P. Ostwald ripening in emulsions: Estimation of solution thermodynamics of the disperse phase. Adv. Colloid Interface Sci. 2003, 106, 261−285. (25) Grillo, I. Applications of stopped-flow in SAXS and SANS. Curr. Opin. Colloid Interface Sci. 2009, 14, 402−408. (26) Bressel, K.; Muthig, M.; Prévost, S.; Gummel, J.; Narayanan, T.; Gradzielski, M. Shaping Vesicles−Controlling Size and Stability by

how this dynamics correlates with the molecular solubility of the oil molecules. For all exchange reactions, a single exponential decay of the scattering intensity with time was observed; therefore, one can assume that the oil exchange takes place by only one mechanism. We also observed a strong slowing down of the exchange rate when increasing the chain length (thus the hydrophobicity and reducing the water solubility) of the oil. This finding suggests that the exchange takes place via diffusion of the oil molecules through the aqueous phase (in a fashion similar to the exchange that takes place during Ostwald ripening24), and coalescence plays hardly any role in these systems. Concentration-dependent measurements do not show a very clear correlation, but this has to be attributed to the fact that by dilution one also changes the composition of the amphiphilic interface, which will also have a role in determining the actual leaving rate of an oil molecule from the droplets. These phenomena would be difficult to measure with techniques other than neutron scattering. Using contrast variation, SANS allows us to differentiate between the different isotopic compositions of the oil in the droplets, giving insights into the mechanism by which the oil exchanges. As so far it is still rather controversial to which extent Ostwald ripening, coalescence, and agglomeration contribute to NE stability, our investigation yields some well-defined insights especially into the relevance of Ostwald ripening for the stability of such emulsified systems. For the formulation scientist, our findings imply that on the timescales investigated here the stability of such NE formulations is mostly governed by the type and solubility of the oil and to a lesser extent by the surfactant corona. This might be a little unfortunate, as there is not necessarily much freedom in the choice of the material that needs to be dispersed. However, such stopped flow experiments clearly allow the oil dynamics in NE systems to be quantified.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.6b03009. Additional information on the compounds, the exact composition of samples, and data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from the BMBF via the project 03GR7TUB PT-J is gratefully acknowledged.

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REFERENCES

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