Influence of the phase behavior on the properties of ionic nanoemulsions prepared by the phase inversion composition method

The low-energy emulsification method phase inversion composition (PIC) was used to prepare O/W nanoemulsions in the W/oleylammonium chloride-oleylamine-C12E10/hexadecane ionic system, where the oleylammonium acted as a cationic surfactant. The results obtained, in terms of phase diagrams and emulsion characteristics, were compared with those obtained in the system W/potassium oleate-oleic acid-C12E10/hexadecane [I. Solè, A. Maestro, C. González, C. Solans, J.M. Gutiérrez, Langmuir 22 (2006) 8326], in which the oleate acted as an anionic surfactant. This study was done in order to extend the application range of the ionic nanoemulsions, not only in anionic systems but also in cationic ones, and in order to deep further into the nanoemulsion formation mechanism. The results show again that to obtain small droplet-sized nanoemulsions it is necessary to cross a direct cubic liquid crystal phase along the emulsification path, and it is also crucial to remain in this phase enough time and to use a proper mixing rate to incorporate all the oil into the liquid crystal. Then, when nanoemulsion forms, the oil is already intimately mixed with all the components, and the nanoemulsification is easier. Structural studies made with both cationic and anionic systems confirmed that the size of the "micelles" that form the cubic phase is the same or slightly smaller than the size of the nanoemulsion droplets obtained, depending on the emulsification path, which seems to point out that the nanoemulsions are formed in both cases by a dilution process of this cubic phase. When further watery solution is added to the cubic liquid crystal, these micelles separate, disrupting the cubic structure, and a small fraction of the surfactant migrates to the water. Moreover, due to the change in pH, the spontaneous curvature increases. Then, the phases in equilibrium are an oil-in-water microemulsion (W(m)) and the oil in excess. However, through this emulsification method, the surfactants can be "trapped" in a lower curvature than the spontaneous one, retaining all the oil nanoemulsified.     

Emulsification through surfactant hydration: the PIC process revisited

We have performed sudden composition changes on a (surfactant + oil + water) system by adding water to a (surfactant + oil) solution. This composition change quenches the system into a metastable oil-in-water emulsion with a population in the 100 nm range. The conditions for a successful quench are as follows: the initial water content should be below a boundary called the "clearing boundary" (CB), the final water content should be sufficiently beyond CB, and the quench should be fast. We have used high purity components to avoid the complex phase separation patterns that occur with low purity ingredients: the surfactant is octaethylenehexadecyl ether (C(16)E(8)) and the oil is hexadecane (C(16)). Under these conditions, we show that the pathway for this type of quench proceeds through the swelling of the reverse micellar phase by the added water and the formation of a sponge phase. Then, further water addition causes the nucleation of oil droplets in this sponge phase, with a size that matches the spontaneous curvature of the sponge phase. Part of the surfactant remains adsorbed on these droplets, and the rest is expelled as micelles that coexist with the droplets. It is concluded that a PIC emulsification will always lead to a bimodal size distribution with surfactant "wasted" in small micelles. This is in contrast with the more efficient PIT emulsification.     

A Three-Step Model for Submicron W/O Emulsion Formation in a Transitional-Phase Inversion Process

A three-step model of the transitional phase inversion (TPI) process for the formation of water-in-oil (W/O) emulsions is presented. Three types of emulsions exist in an emulsification process at different oil–water ratios and hydrophilic–lipophilic balance (HLB). A stable W/O emulsion was obtained using Sorbitan oleate (Span 80) and polyoxyethylenesorbitan monooleate (Tween 80) with a specified HLB and oil volume fraction. Oil was added into water, which contained the water-soluble surfactant, to dissolve the oil-soluble surfactant. This route allowed TPI to occur, and an interesting emulsification process was observed by varying the HLB, which corresponded to the change in the oil–water ratio. Two types of emulsions in the emulsification process were found: transition emulsion 1 (W/O/W high internal phase emulsion) and target emulsion 2 (W/O emulsion with low viscosity). This study describes the changes that occurred in the emulsification process.     

Nanoemulsions prepared by a two-step low-energy process

A simple low-energy two-step dilution process has been applied in oil/surfactant/water systems with pentaoxyethylene lauryl ether (C12E5), dodecyldimethylammonium bromide, sodium bis(2-ethylhexyl)sulfosuccinate, sodium n-dodecyl sulfate-pentanol, and hexadecyltrimethylammonium bromide-pentanol. Appropriate formulations were chosen for the concentrate to be diluted with water to generate oil-in-water (O/W) emulsions or nanoemulsions. For the system of decane/C12E5/water, bluish, transparent nanoemulsions having droplet radii of the order of 15 nm were formed, only when the initial concentrate was a bicontinuous microemulsion, whereas opaque emulsions were generated if the concentrate began in an emulsion-phase region. Nanoemulsions generated in the system decane/C12E5/water have been investigated both by dynamic light scattering (DLS) and contrast-variation small-angle neutron scattering (SANS). The SANS profiles show that nanodroplets exist as spherical core-shell (decane-C12E5) particles, which suffer essentially no structural change on dilution with water, at least for volume fractions phi down to 0.060. These results suggest that the nanoemulsion droplet structure is mainly controlled by the phase behavior of the initial concentrate and is largely independent of dilution. A discrepancy between apparent nanoemulsion droplet sizes was observed by comparing DLS and SANS data, which is consistent with long-range droplet interactions occurring outside of the SANS sensitivity range. These combined phase behavior, SANS, and DLS results suggest a different reason for the stability/instability of nanoemulsions compared with earlier studies, and here it is proposed that a general mechanism for nanoemulsion formation is homogeneous nucleation of oil droplets during the emulsification.     

The effect of a lipophilic drug,felodipine, on the formation of nanoemulsions upon phase inversion induced by temperature variation

The correlation between a dispersed phase/dispersion medium interfacial tension σ at a storage temperature of 22°C and the dispersity and stability of oil-in-water miniemulsions, which result from temperature-induced phase inversion, has been revealed for hydrocarbon/polyoxyethylene(4)lauryl ether/water systems (in the presence and absence of felodipine) with the help of conductometry, tensiometry, and dispersion analysis. At σ < 3.5 × 10^–6 N/m, oil-in-water nanoemulsions, which have narrow monomodal particle size distributions and are stable for a month, are a fortiori formed. Felodipine has been shown to serve as a cosurfactant, which is incorporated into the adsorption layer of a basic stabilizing nonionic surfactant. Therewith, σ values increase and the temperature of phase inversion decreases, while the concentration of the basic surfactant in an optimal composition must be substantially reduced. A heptane/water nanoemulsion (droplet size of 75 nm) stabilized with a basic nonionic surfactant and Tween 80 exhibits a high solubilization capacity with respect to felodipine and ensures its efficient mass transfer through a model membrane.     

Phase behavior and nano-emulsion formation by the phase inversion temperature method

Formation of oil-in-water nano-emulsions has been studied in the water/C12E4/isohexadecane system by the phase inversion temperature emulsification method. Emulsification started at the corresponding hydrophilic-lipophilic balance temperature, and then the samples were quickly cooled to 25 degrees C. The influence of phase behavior on nano-emulsion droplet size and stability has 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 smallest droplet sizes were produced in samples where the emulsification started in a bicontinuous microemulsion (D) phase region or in a two-phase region consisting of a microemulsion (D) and a liquid crystalline phase (L(alpha)). Although the breakdown process of nano-emulsions could be attributed to the oil transference from the smaller to the bigger droplets, the increase in instability found with the increase in surfactant concentration may be related to the higher surfactant excess, favoring the oil micellar transport between the emulsion droplets.     

HYDRODYNAMIC AND THERMODYNAMIC EFFECTS IN PHASE INVERSION EMULSIFICATION PROCESS OF EPOXY RESIN IN WATER

The mechanism of phase inversion emulsification process （PIE） was studied for waterborne dispersion of highly viscous epoxy resin using non-ionic polymeric surfactants. Drop deformation and breakup, rheological properties, conductivity, and particle size measurements reveal the micro-structural transition amid emulsification. It is revealed that strong flow causes water drop to burst with the formation of droplets and huge interface. Phase inversion corresponds to an abrupt rheological transition from a type of viscous melt with weak elasticity to a highly elastic type of aqueous gel. This implies that the phase inversion equivalent to a curvature inversion. Based on this, a geometric model is postulated to correlate process variables to the particle size. The coverage and conformation of the surfactant plays key role for the particle size of the final emulsion. The interactions of thermodynamic and hydrodynamic effects are also discussed. It is concluded that the thermodynamics control the PIE while the hydrodynamics drives the creation of interface and involves every step of PIE.     

Oil/water droplet formation by temperature change in the water/c(16)e(6)/mineral oil system

Droplet sizes of oil/water (O/W) nanoemulsions prepared by the phase inversion temperature (PIT) method, in the water/C16E6/mineral oil system, have been compared with those given by a theoretical droplet model, which predicts a minimum droplet size. The results show that, when the phase inversion was started from either a single-phase microemulsion (D) or a two-phase W+D equilibrium, the resulting droplet sizes were close to those predicted by the model, whereas, when emulsification was started from W+D+O or from W+D+Lalpha (Lalpha = lamellar liquid crystal) equilibria, the difference between the measured and predicted values was much higher. The structural changes produced during the phase inversion process have been investigated by the 1H-PFGSE-NMR technique, monitoring the self-diffusion coefficients for each component as a function of temperature. The results have confirmed the transition from a bicontinuous D microemulsion at the hydrophile-lipophile balance (HLB) temperature to oil nanodroplet dispersion in water when it is cooled to lower temperatures.     

The rheology of aqueous emulsions prepared by direct emulsification and phase inversion from a high viscosity alkyd resin

A comparison of the rheological properties of dispersions of an alkyd resin in water prepared by direct emulsification and phase inversion has been conducted. These dispersions have application as the base dispersion in the manufacture of the new generation of water based gloss paints. An experimental investigation of the effect of dispersed phase fraction, droplet size and dispersion age on the rheological properties of dispersions produced by each emulsification route has been carried out. The droplet size distributions of the dispersions are also characterised. It was found that phase inversion always gave a smaller droplet size distribution than direct emulsification. Surprisingly it was found that for a given dispersed phase fraction, the dispersions with a smaller droplet size, produced by the phase inversion route, have a lower zero shear rate viscosity than those produced by the direct emulsification route. The rheology of the direct emulsification samples was also observed to change with age, whilst with phase inversion samples the rheology was stable. It is proposed that this and other differences observed between the two methods of manufacture can be associated to the presence, or otherwise, of excess surfactant in the aqueous phase.     

Phase behavior, self-assembly, and emulsification of tween 80/water mixtures with limonene and perfluoromethyldecalin

The phase behavior, microstructure, and emulsification of polyoxyethylene (20) sorbitan monooleate (Tween 80), water, and d-limonene (LM) or perfluoromethyldecalin (PFMD) has been studied by small-angle X-ray scattering and polarizing optical microscopy. In the Tween 80/water binary system, a micellar solution (L(1)), a hexagonal (H(1)) phase, and a water-swellable isotropic surfactant liquid (L(2)) phase are successively formed at 25 °C. LM can be solubilized into all of the phases formed by Tween 80/water mixtures, whereas no solubilization of PFMD occurs. The L(2) phase was found by small-angle neutron scattering to be bicontinuous with low interfacial curvature. Added water swells and amplifies the pre-existing amphiphilic structure. The stability of oil-in-H(1) complex emulsions is found to be sensitive to changes in structure that accompany solubilization.     

Globular and bicontinuous phases of nonionic surfactant films

Nonionic surfactants of the alkyloligoethylene oxide type form, with water and oil, a range of isotropic a liquid crystalline phases. We analyse the phase behaviour using the flexible surface model and argue that the strong temperature dependence is caused by the fact that the monolayer spontaneous curvature decreases strongly with increasing temperature. This is exemplified with the behaviour of bicontinuous microemulsions, showing a symmetric behaviour around the balanced state, globular microemulsions, behaving as hard spheres near the emulsification failure boundary, and sponge phases appearing when the monolayer spontaneous mean curvature is towards the abundant solvent. It is argued that there is a hierarchy of free energy contributions determining the preferred aggregate shape/phase. With a given oil-water ratio and a surfactant concentration that fixes the polar/apolar interfacial area, the most important free energy contribution comes from having a mean curvature close to the spontaneous curvature. The Gaussian curvature and the entropy terms become important when selecting between structures of similar mean curvature. At higher concentrations, surface forces and higher order elastic terms become significant.     

Microemulsions from silicone oil with an anionic/nonionic surfactant mixture

Microemulsion phases have been prepared for the first time from the silicone oil "M(2)" (hexamethyldisiloxane) and a surfactant mixture of a nonionic surfactant "IT 3" (isotridecyltriethyleneglycolether) and an ionic surfactant Ca(DS)(2) (calciumdodecylsulfate). For such a surfactant mixture the hydrophilicity of the system can be tuned by the mixing ratio of the two components. With increasing IT 3 content, the surfactant mixtures show a L(1)-phase, a wide L(α)-region and a narrow L(3) sponge phase. For constant temperature, two single phase channels exist in the microemulsion system. The lower channel (low IT 3 content) ends in the middle of the phase diagram with equal amounts of water and oil, the upper channel begins with the L(3)-phase and passes all the way to the oil phase. Conductivity data show that the upper channel has a bi-continuous morphology up to 40% oil while the lower channel consists of oil droplets in water. In contrast to previous studies on nonionic systems, the two single phase channels are not connected and microemulsions with equal amount of oil and water do not have a bicontinuous structure.     

O/W Nanoemulsion After 15 Years of Preparation: A Suitable Vehicle for Pharmaceutical and Cosmetic Applications

The application of nanoemulsions is due to have good stability, uniform spreading and enhance active penetration upon skin. Nanometer emulsions can be obtained by low-energy emulsification method. The required hydrophilic and lipophilic balance indicates the better balance of emulsifier for optimum system emulsification. Emulsion stability is evidently controlled for the properties of the adsorbed layer formed in the surface of its globules, know as potential zeta. The aim of this work was to evaluate the oil/water nanoemulsion of formulation obtained after 15 years of preparation. The results suggested that the nanoemulsion have performed stability for many years.     

细小乳状液的制备

For preparing O/W miniemulsions containing soybean oil and silicone oil, three methods, phase inversion emulsification, D-phase emulsification, reformed D-phase emulsification were tested by using Brij92, 97, 98 and Tween 80, 85, 60, 20 and Span 80, 60 mixed surfactants. It was found that the O/W miniemulsions of soybean oil and silicone oil can not be formed by phase inversion emulsification method, but can be formed by the two other methods. The results of emulsification showed that if gel emulsion, in which fine oil droplets disperse in continuous phase with high surfactant content, appears during the emulsification process, the O/W miniemulsions can be formed by simply diluting with water.     

Oil-in-water nanoemulsions for pesticide formulations

A two-step process for formation of nanoemulsions in the system water/poly(oxyethylene) nonionic surfactant/methyl decanoate at 25 degrees C is described. First, all the components were mixed at a certain composition to prepare a microemulsion concentrate, which was rapidly subjected into a large dilution into water to generate an emulsion. Bluish transparent oil-in-water (O/W) nanoemulsions were formed only when the concentrate was located in the bicontinuous microemulsion (BC) or oil-in-water microemulsion (Wm) region. The existence of an optimum oil-to-surfactant ratio (R(os)) in the BC or Wm region indicates that both the phase behavior and the composition of the concentrate are important factors in nanoemulsion formation. To demonstrate potential applications of these systems, they were employed to formulate a water-insoluble pesticide, beta-cypermethrin (beta-CP). The nanoemulsion was compared with a commercial beta-CP microemulsion in terms of the stability of sprayed formulations.     

Effect of salts on the phase behavior and the stability of nanoemulsions with rapeseed oil and an extended surfactant

For many decades, the solubilization of long-chain triglycerides in water has been a challenge. A new class of amphiphiles has been created to overcome this solubilization problem. The so-called "extended" surfactants contain a hydrophilic-lipophilic linker to reduce the contrast between the surfactant-water and surfactant-oil interfaces. In the present contribution, the effects of different anions and cations on the phase behavior of a mixture containing an extended surfactant (X-AES), a hydrotrope (sodium xylene sulfonate, SXS), water, and rapeseed oil were determined as a function of temperature. Nanoemulsions were obtained and characterized by conductivity measurements, light scattering, and optical microscopy. All salting-out salts show a transition from a clear region (O/W nanoemulsion), to a lamellar liquid crystalline phase region, a clear phase (bicontinuous L(3)), and again to a lamellar liquid crystalline phase region with increasing temperature. For the phase diagrams with NaSCN and Na(2)SO(4), only one clear region (O/W nanoemulsion) was observed, which turns into a lamellar phase region at elevated temperatures. Furthermore, the stability of the nanoemulsions was investigated by time-dependent measurements: the visual observation of phase separation, droplet size by dynamic light scattering (DLS), and optical microscopy. The mechanism of the different phase transitions is also discussed.     

Preparation of positively charged oil/water nano-emulsions with a sub-PIT method

The phase inversion temperature (PIT) method is generally used to prepare nonionic surfactant stabilized nano-emulsions because of its low energy and surfactant consumption. The emulsion droplets are usually negatively charged because of the selective adsorption of OH(-) onto the droplet surfaces. In this work, positively charged oil/water nano-emulsions were prepared by adding a cationic surfactant to the system. The cationic molecules change the spontaneous curvature of the surfactant layers and raise the PIT above 100 °C. The PIT can be depressed by addition of NaBr, as shown by conductivity measurements and equilibrium phase behavior. Therefore, these nano-emulsions can be prepared by the PIT method. We found that the formation of the nano-emulsions did not require a cross-PIT cycle. The mechanism of the emulsification is the formation of mixed swollen micelles that can solubilize all the oil above a "clearing boundary", followed by a stir-quench to a temperature where these droplets become metastable emulsions. The zeta potential of the emulsion droplets can be easily tuned by varying the cationic surfactant concentrations. Due to electrosteric stabilization, the resulting nano-emulsions are highly stable, thus could find significant applications in areas such as pharmaceuticals, cosmetics and food industries.     

Structure and dynamics of a sponge phase in the methyl delta-aminolevulinate/monoolein/water/propylene glycol system

The structural effect caused by the addition of up to 16% (w/w) of the hydrochloride salt of delta-aminolevulinic acid (ALA, HOOC-CH2-CH2-CO-CH2-NH2HCl) or its methyl ester (m-ALA) to the sponge phase formed of monoolein/water/propylene glycol was investigated by means of crossed polarizers, small angle X-ray diffraction (SAXD) and nuclear magnetic resonance diffusometry (NMRD). Inspection with crossed polarizers revealed that additions of 4-16% (w/w) m-ALA transformed the isotropic bicontinuous sponge phase partly (4-10%) or completely (13 and 16%) into an anisotropic lamellar phase, indicating that m-ALA has a flattening effect on the bilayer curvature. The addition of 16% (w/w) ALA did not show any effect on the sponge phase. By addition of water to the anisotropic m-ALA samples, isotropic liquids were re-formed. The SAXD data for the isotropic liquids showed a diffuse Bragg peak and the NMRD self-diffusion coefficients for the drug (m-ALA) and the components of the original sponge phase (monoolein, water and propylene glycol) were shown to be essentially constant for 0-16% (w/w) added m-ALA. These results confirmed the hypothesis that the re-formed isotropic phases were indeed sponge phases. Water, for example, showed a diffusion coefficient of 3.1-3.9x10(-10)m(2)s(-1) in the sponge phase, compared to 5.3-5.7 x 10(-10)m2s(-1) in relevant water/propylene glycol solutions or 2.3 x 10(-9)m2s(-1) in pure water. The reduction can be explained as a consequence of the microstructure (congruent monoolein bilayer) of the sponge phase and of the viscosity effect caused by propylene glycol and m-ALA.     

Salting-out effect induced by temperature cycling on a water/nonionic surfactant/oil system

This paper presents original effects induced by temperature cycling on the transitional phase inversion of emulsions, stabilized by a nonionic polyethoxylated C18E6 surfactant model. The phase inversion follow-up is performed by electrical conductivity measurements, which involves focusing the study on the shape and location of the emulsion inversion region. In that way, new observations are brought out as a gradual evolution of the emulsion inversion along the cycling process. Two alternative approaches are considered for tackling these results: (i) first, a molecular approach regarding the particular organization and rearrangement of water clusters surrounding the surfactant polymer polar head, and (ii) second, a thermodynamic approach only considering the whole Gibbs free energy of the system. The volumic approaches are transposed, here, to the water/oil interface, and disclose that the phase inversion zone is included in a metastable region, able to stabilize for a given temperature, either metastable O/W emulsions or stable W/O ones. In that way, this study proposes novel and complementary insights into the phenomena governing the emulsion phase inversion.