Hydrophilic-lipophilic Properties Research Articles

The Response Surface Methodology for Assessment of HLB Values of Mixtures of Non-Ionic Surfactants Using Parameters from Their π-A Isotherms.

The aim of the work was to determine important parameters of the course of π-A isotherms, which can determine the HLB (hydrophilic-lipophilic balance) value of surfactant mixtures with selected structural features, such as a straight or branched hydrocarbon chain and a double bond, using RSM (response surface methodology) computational methods. Mixtures of surfactants derived from fatty acids and sorbitan with specific HLB values were evaluated by Langmuir trough. The resulting elasticity modules (ELM) and molecules surfaces (SAM) were evaluated via response surface methodology and respective equations were calculated. The π-A isotherm determined in a Langmuir trough and the ELM and SAM parameters determined on the basis of this isotherm may be useful for determining the HLB of a fixed surfactant mixture. The RSM method used, in which ELM and SAM were assumed as two independent variables, can be a useful technique for tracking the influence of individual molecular characteristics on the hydrophilic-lipophilic properties of mixtures of surfactant compounds. Changes in HLB as a dependent variable can be described as a function of ELM and SAM.

Adsorption of Hydrophobic Ions on Environmentally Relevant Sorbents.

Environmental monitoring and remediation often requires the collection of harmful substances from aqueous solutions. Absorption with solids is a useful technique for binding such substances even at very low concentration levels. Many of these contaminants are weak acids or bases. Some novel, nonionic polymeric sorbents, such as hypercrosslinked polymers or polymers with balanced hydrophilic-lipophilic properties (HLB) have been found to bind weak acids and bases with high distribution coefficients even at pH values where these compounds are almost completely ionized (typically near pH 7). To understand this phenomenon and its practical consequences, we have experimentally studied the adsorption of ionizable weak acids and bases as a function of pH and ionic strength on a the OASIS® HLB sorbent. Not surprisingly, the ionic forms of the weak acids and bases were found to be much less bound in the aqueous solution than their neutral forms. In spite of this, OASIS® HLB binds weak acids and bases around pH 7 considerably better than typical hydrophobic sorbents. The high overall distribution coefficients around pH 7 could be explained by two factors. One is that on OASIS® HLB, and on some other novel polymeric sorbents, the binding constant of the moderately hydrophobic neutral form is on the order of 100,000, i.e., much higher than on typical hydrophobic sorbents. Thus, even if the proportion of the neutral form in solution is only around 1% near pH 7, the adsorption of the neutral form is still significant. On the other hand, the binding of the apparently hydrophilic ionized forms occurs with distribution coefficients well above 100. The distribution coefficient of the ionic form appears to depend on ionic strength and the presence of competing ions. Adsorption of the ionic forms is found to be very similar to the adsorption of ionic surfactants. The pH dependence of the total adsorption of neutral and ionic forms together, is found to be steep around pH 7, and therefore the varying pH of natural waters may strongly influence the binding efficiency in practical applications, such as the collection (concentration) of contaminants or their passive sampling.

Erectcyanthins A-C from marine sponge Hyrtios erectus: anti-dyslipidemic agents attenuate hydroxymethylglutaryl coenzyme A reductase

Bioactivity-steered chromatographic purification of the solvent extract of marine sponge Hyrtios erectus (Thorectidae) led to the isolation of three undescribed cyanthiwigin-type diterpenoids, erectcyanthins A-C. Erectcyanthin B exhibited comparable attenuation activity against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (IC50 0.07 mM) with that displayed by anti-dyslipidemic agent atorvastatin (IC50 0.08 mM). Comparatively greater antioxidant properties of erectcyanthin B (IC50 ∼ 0.4 mM) than that displayed by erectcyanthin A (IC50 ∼ 0.5 mM), erectcyanthin C and the standard α-tocopherol (IC50 1.5–1.7 mM) against oxidants also corroborated its promising bioactivity. Erectcyanthin B exhibited considerably greater anti-inflammatory activities (IC50 0.88–1.09 mM) than other erectcyanthin analogues in the series. The potential anti-dyslipidemic activity of erectcyanthins was linearly correlated with electronic parameter (topological polar surface area ∼ 74.6) along with balanced hydrophilic-lipophilic properties (logarithmic octanol-water partition coefficient 1.76). This study recognized the anti-dyslipidemic property of erectcyanthin B as a promising pharmaceutical lead.

Antioxidant spiropharanone, an undescribed variant of trans-decalin spiro-γ-lactone, from pharaoh cuttlefish Sepia pharaonis: Twin inhibitors of inflammatory 5-lipoxygenase and serine protease dipeptidyl peptidase-4.

Marine pharaoh cuttlefish Sepia pharaonis (family Sepiidae) is regarded as an economically important class of cephalopod in the coastal Mediterranean and Asian regions. Bioassay-guided chromatographic purification of solvent extract of S. pharaonis led to the identification of a trans-decalin based spirolactone, spiropharanone, which was characterized as 1-hydroxy-7-(4'-methoxy-3-methylbut-2-enyl)-3,9,15-trimethyl-8-oxo-octahydro-5H-spiro[furan-8,9-naphtho]-8-yl-acetate by spectroscopic techniques. Spiropharanone exhibited significantly greater anti-inflammatory activity by attenuating pro-inflammatory 5-lipoxygenase (IC50 1.02mM) than the non-steroidal drug ibuprofen (IC50 4.61mM, p≤.05). Superior antioxidant properties of spiropharanone against free radicals (EC50 ~1.20mM) and other oxidants (hydroxyl [EC50 0.97mM] and superoxide [EC50 1.47mM] scavenging) also reinforced its promising anti-inflammatory activity. The studied spiropharanone also exhibited significant attenuation toward insulin secretion regulating enzyme dipeptidyl peptidase-4 (IC50 0.92mM) recognizing its anti-hyperglycemic potential. Significantly higher electronic properties (topological polar surface area ~100) combined with balanced hydrophilic-lipophilic properties (partition coefficient of logarithmic octanol-water ~3) and lesser docking parameters of spiropharanone demonstrated that the compound could be utilized as an important bioactive lead against oxidative stress, inflammation, and hyperglycemic-related ailments. PRACTICAL APPLICATIONS: Nutritionally rich edible marine pharaoh cuttlefish Sepia pharaonis occupies a prominent place among seafood fisheries owing to the presence of bioactive nutrients and functional food ingredients. These marine cuttlefish are widely distributed along the Asian and Mediterranean coasts, and consumed as culinary delicacy for decades. An undescribed trans-decalin spirolactone, spiropharanone was isolated from the organic extract of S. pharaonis based on bioactivity-assisted sequential chromatographic fractionation. Spiropharanone displayed promising antioxidant potential along with attenuation properties against inducible pro-inflammatory 5-lipoxygenase and insulin secretion regulating enzyme dipeptidyl peptidase-4. This study established the ameliorating potential of a naturally derived marine food constituent against inflammatory and diabetic ailments, and thus anticipated as functional food lead in pharmaceutical formulations towards inflammation and maintaining glucose homeostasis.

Drug design of medicinal products on the basis of natural cardiosteroids

The aim. The article describes works about designing a structure, predicting of biological activity and the chemical transformation of natural cardiosteroids to obtain promising drugs with specified properties.Materials and methods. An effective modified method for the synthesis of aldimines of cardenolides, based on the interaction of natural cardenolides with organic amines, is proposed. The abnormal physical and chemical properties of bis-ketoimines, which consist in their resistance to hydrolysis and increased polarity, are revealed.Results. It is revealed that electrostatic fields play a decisive role in cardiotonic activity, which should be located in the form of a sandwich – in the α-plane there is a positive charge and in the β-plane is negative. The presence of a negative field at C3 is mandatory and the activity is higher if this negative field is extended further (the sugar component of the conditioned configuration, which does not violate the charges of the α- and β-planes). It is shown why the molar activity (biological activity expressed in moles of substance per kg of animal mass) of cardenolide glycosides is higher than their aglycones, that is, the sugar component contributes to the activity through electron fields, and not only due to changes in the hydrophilic-lipophilic properties of the substance.Conclusions. The hypothesis of the existence of a phenomenon of non-inducing binding to Na +, K + -AT Phase, in which the substance acts as an antidote for active cardiosteroids is formulated.A detailed analysis of this relatively exceptional case involves the simultaneous occurrence of two isomerism – conformational (conformers) and geometric in the synthesis of aldimines of cardenolides

Antioxidant and antiinflammatory secondary metabolites from the Asian green mussel Perna viridis.

The Asian green mussel, Perna viridis is a nutritious health food in the estuarine and coastal sea beds of the Arabian Sea along the west coast of India. In the present study, bioactivity-guided purification of the chloroform fraction of the methanolic extract of P. viridis was carried out. The isolated secondary metabolites were characterized by spectroscopic experiments, and their antioxidative/antiinflammatory properties were evaluated. The titled compounds were characterized as 3-hydroxy-13-vinyl-dodecahydro-11-phenanthrenone (1), 4,4,9-trimethyl-13-vinyl-dodecahydro-2-phenanthrenone (2), 11,20-dihydroxy-6,6-dimethyl-decahydro-5H-benzo[h]naphtho[1,2-c]chromene-16-carbaldehyde (3), 16-acetyl-20-hydroxy-6,6-dimethyl-dodecahydro-5H-benzo[h]naphtho[1,2-c]chromen-12-one (4), cholest-5-en-3β-3-yl-(30-hydroxy-3-methyl-36-methyleneundeca-30E,34E-dienoate) (5), and cholest-5-en-3β-3-yl-((E)-33-oxooct-31-enoate) (6). No significant differences in the antioxidant activities of the compounds with chromene-16-carbaldehyde (3) and chromen-12-one (4) functionalities (IC50 0.52-0.68mg/ml) vis-à-vis the positive control, α-tocopherol (IC50 0.65-0.76mg/ml) were registered. The studied compounds, 1-4, displayed potential antiinflammatory activities against pro-inflammatory 5-lipoxygenase (5-LOX) (IC50 <1mg/ml). The balanced hydrophilic-lipophilic properties and lower steric values of the studied compounds, 1-4, were correlated with their bioactive potentials. PRACTICAL APPLICATIONS: The edible bivalve green mussels, P. viridis, are broadly available in the estuarine and coastal regions of the Indian Peninsula. The sequential chromatographic purification of the chloroform fraction of the methanolic extract of P. viridis led to the identification of six pure secondary metabolites. The metabolites with substituted chromene-16-carbaldehyde and chromen-12-one functionalities displayed potential antioxidative and antiinflammatory activities compared to other studied compounds. These bioactive metabolites could be used in functional food formulations and as antioxidant leads in medicinal food applications.

Aquivion-Carbon Composites with Tunable Amphiphilicity for Pickering Interfacial Catalysis.

A key demand in biomass conversion is how to achieve high reactivity with immiscible reagents with the use of neither cosolvents nor additives. Pickering interfacial catalysis encompassing the design of amphiphilic catalysts behaving concomitantly as emulsifiers offers an elegant solution. In this study, we prepared a systematic series of amphiphilic Aquivion-carbon composites by the hydrothermal carbonization of guar gum with Aquivion perfluorosulfonic superacid. By tuning the Aquivion-carbon composition, materials with tunable hydrophilic-lipophilic properties could be prepared, showing high versatility for conducting biphasic reactions without stirring. In particular, an optimal formulation based on 5:1 Aquivion-carbon could be developed, showing high activity in the transesterification reaction of glyceryl trioleate with methanol at 100 °C with good reusability due to the genesis of stable Pickering emulsions.

Synthesis and Interfacial Tensions of Sodium p-Dimethyl Dodecylbenzene Sulfonates

Abstract Six isomers of sodium para-dimethyl dodecylbenzene sulfonates (p-S12) were synthesized by a series of reactions. The surface tension of the isomers p-S12 in an aqueous NaCl solution (4000 mg/L) was measured. From the data the following parameters were calculated: critical micelle concentration (CMC), the surface tension at the CMC (γ CMC ), the surface excess concentration at surface saturation (Γ max) and the area per molecule at surface saturation (A s min). The A s min increased and the Γ max decreased when the aromatic nucleus moves to the center of long-chain alkyl group. The dynamic interfacial tensions (DIFT) between p-S12 in 4000 mg/L NaCl aqueous solution and five n-paraffins were measured by using a spinning drop technique. The DIFT of the p-S12 showed the characteristic that the interfacial tension (IFT) is low at the beginning, then increases, reaches a maximum value, and finally continues to decrease until it reaches a stable value. By the measurement of alkane carbon number for the minimum IFT, n min, of the six isomers solutions, we found that the n min firstly decreases and then increases when the aromatic nucleus moves to the long-chain alkyl group. This phenomenon is due to the differences of hydrophilic-lipophilic properties and the structure of the p-S12 isomers.

Impact of nanoclay and carbon microfiber in combating the deterioration of asphalt concrete by non-chloride deicers

This preliminary laboratory research aims to explore the impact of nanoclay and carbon microfiber in combating the deterioration of asphalt concrete by non-chloride deicers. Modified boiling water test, electrochemical impedance spectroscopy (EIS) and contact angle test were employed to investigate the effects of nanoclay and carbon microfiber on asphalt concrete in the presence of four non-chloride deicers, namely, dipotassium succinate, potassium formate, potassium propionate and potassium acetate. The results indicated that the incorporation of small amount of nanoclay in asphalt concrete produced a notably improved stripping resistance and reduced moisture susceptibility, while the addition of carbon microfiber increased moisture susceptibility. The deterioration effect of the four non-chloride deicers on asphalt mastic was discussed based on their molecule’s hydrophilic-lipophilic properties.

The study of steroid distribution in emulsions by the spin probe method

The solubility of the active substance, which determines its dispersed state in a dosage form, is a significant pharmaceutical factor for providing the required functional characteristics of a medicinal product, its effectiveness, safety and, if necessary, bioavailability.Aim. To study the behavior of spin probes based on steroids in some solvents, micelles of nonionic surfactants, as well as emulsions both of type 1 and type 2 with a different composition of excipients in order to predict bioavailability, efficacy and safety of medicinal products with steroids.Materials and methods. The studies were carried out by the spin probe method. Two spin probes based on steroids with different localization of the nitroxide radical in their molecules were used.Results. The disperse state and localization of steroid molecules in some solvents, surfactant micelles and emulsions both of type 1 and type 2 were identified using the shape of EPR spectra, the isotropic constant values and the rotational correlation time of two different spin probes. It has been found out that the spin probes based on steroids with different hydrophilic-lipophilic properties are distributed differently in the dispersion medium and in the dispersed phase of emulsions. The emulsion type, the chemical nature, the composition and polarity of the dispersion medium and the dispersed phase also cause differences in distribution of steroids in emulsions.Conclusions. Different localization and disperse state of steroids in vehicles can affect the effectiveness of their pharmacological action, bioavailability in different routes of administration and the safety of drugs. In the pharmaceutical development of drugs it is necessary to study the solubility of steroids, their distribution between the dispersed phase and the dispersion medium of emulsions, the disperse state in the vehicles, as well as to carry out biopharmaceutical and/or pharmacological screening studies in order to select the optimal composition of the medicinal product.

Design, facile synthesis and anthelmintic activity of new O-substituted 6-methoxybenzothiazole-2-carbamates. Part II.

In the framework of pursuing the design and synthesis of a new series of substituted 6-methoxybenzothiazole-2-carbamates as potential anthelmintics, and as a continuation of the expended efforts in part I, we have set out to develop novel compounds with enhanced anthelmintic activity by blocking the 6-position of benzothiazole with side chains of different polarities. Guided by the findings in part I, and reporting the paramphistomicidal activity of oxadiazoline derivatives V and VI, we aimed to synthesize target benzothiazoles designed to comprise some planar heterocyclic ring systems, namely, 1,3,4-oxadiazoles and 1,2,4-triazoles, bearing a variety of hydrophobic and hydrophilic components. The synthesis of the desired compounds was primarily achieved by cyclization of 6-acetohydrazide, 1. The in vitro paramphistomicidal activity of all synthesized carbamates was evaluated. Four synthesized carbamates exhibited notable activity. Compound 24, methyl 6-[(5-(4-bromophenacylsulfanyl)-[1,3,4]-oxadiazol-2-yl)methoxy]benzothiazole-2-carbamate, displayed an equipotent effect to the reference drug oxyclozanide at a concentration of 80 μg mL-1; compounds 9, 10 and 23 showed high orders of anthelmintic effect. A structural computational study on the polar nature and hydrophilic-lipophilic properties of the synthesized carbamates was undertaken to discuss their structure-activity relationship (SAR). Besides, pharmacophore mapping was performed using eight active compounds as a training set. The generated pharmacophore model revealed five common features and was validated using fenbendazole, triclabendazole and triclabendazole sulfoxide.

Design, facile synthesis and anthelmintic activity of new O-substituted 6-methoxybenzothiazole-2-carbamates

Hypothesis for designing 6-substituted benzothiazolecarbamate prototype anthelmintics having diversities in flexibility and rigidity of substituents with different polar nature and hydrophilic–lipophilic properties.

Impact of moisture and plasticizer properties on polymer–plasticizer physical mixing performance

ABSTRACTThe ability for polymers and additives to physically mix in many industrial applications is dictated by a combination of kinetic and thermodynamic factors. The presence of moisture may complicate the mixing performance as water can interact at various degrees with each of the components; this depends on the hydrophilicity of the materials. In this study, the physical mixing behavior of a ternary system consisting of a hygroscopic polymer (copovidone), a plasticizer, and water was examined. Three different liquid plasticizers with a range of hydrophilic–lipophilic properties and viscosities were evaluated for their physical mixing performance and the impact of their water content. Inverse gas chromatography was introduced as a new method for measuring the surface characteristics of the physical mixtures to quantify the mixing performance. Through the application of the Flory–Huggins model to understand the thermodynamic behavior of the system, it was shown that mixing was less effective in a system of high water content for a hydrophobic plasticizer. However, the underlying thermodynamic unfavorability of such a system could be overcome by kinetic influence to provide a good mixing performance. Specifically, as the viscosity of the plasticizer decreased, the influence of the thermodynamic characteristics was found to become less apparent. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41679.

In situ emulsion copolymerization of methyl methacrylate and butyl acrylate in the presence of SiO2 with various surface coupling densities

Poly(methyl methacrylate-co-butyl acrylate) (poly(MMA-co-BA))/SiO2 nanocomposite particles with various morphologies were prepared through in situ emulsion copolymerization of methyl methacrylate and butyl acrylate using surface 3-(methacryloyloxy) propyl trimethoxysilane (MPS)-modified SiO2 nanoparticles as nanofillers. The surface MPS-coupling density of SiO2 nanoparticles could influence the hydrophilic–lipophilic properties of SiO2 nanoparticles and subsequently influence the particle morphology of poly(MMA-co-BA)/SiO2 nanocomposite particles. With the increase of the surface MPS-coupling density of SiO2 nanoparticles, the morphology of nanocomposite particles changed from a raspberry-like one to a guava-like one. A formation mechanism of nanocomposite particles with various morphologies was proposed on the basis of the results of polymerization kinetics, particle size evolution in the process of polymerization, and particle size and morphology of the final nanocomposite particles.

Pluronic Block Copolymers Inhibit Low Density Lipoprotein Self‐Association

Little is known about exogenous inhibitors of low-density lipoprotein (LDL) aggregation. The search for nontoxic and bioavailable inhibitors of LDL aggregation is of interest, especially considering that the suppression of the aggregation of LDL might represent a therapeutic approach. We hypothesized that amphiphilic copolymers of propylene oxide and ethylene oxide, the so-called Pluronic block copolymers, can be used to influence the aggregation of LDL. In this work we used Pluronic® P85, L61 and F68. A comparative study of the effects of Pluronic block copolymers with various hydrophilic-lipophilic properties on the aggregation process of LDL showed that Pluronic copolymers with strong hydrophobic properties (P85 and L61) at concentrations close to or greater than the respective critical concentration of micelle formation inhibited the aggregation process of LDL; however, the "hydrophilic" Pluronic F68 had no effect on the aggregation of LDL at any concentration. Thus, the study demonstrated for the first time that Pluronic® block copolymers inhibit LDL self-association. The possibility of modulating the aggregation of LDL by various Pluronic copolymers can be regarded as a prerequisite in the creation of new types of anti-atherosclerotic drugs.

Sucrose esters with various hydrophilic–lipophilic properties: Novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction

Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic–lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic–lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic–lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic–lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3–16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System.

The synthesis of MP–CDCA conjugates and dissolution kinetics of model cholesterol gallstones

The comb-like copolymers of polycarboxylic acid were synthesized and then reacted with chenodeoxycholic acid (CDCA) to obtain a series of conjugates, MP n–CDCA, where n is the number of the groups of oxyethylene in each graft chain. This was confirmed by infrared spectroscopy and thin-layer chromatography. We investigated the effects of dissolving model cholesterol gallstones with the MP n–CDCA conjugates in phosphate-buffered saline at pH 7.4. The dissolution rates of CDCA, MP40–CDCA, MP30–CDCA, MP20–CDCA and MP10–CDCA were 5.33, 5.717, 17.59, 6.868 and 9.615 × 10 −7 kg m −2 s −1, micellar solubilities were 0.2431, 3.095, 12.972, 5.248 and 5.790 kg m −3 and total resistances were 5.33, 5.717, 17.59, 6.868 and 9.615 × 10 −7 kg m −2 s −1, respectively. These studies suggested that the interfacial resistance was the dominant rate-determining factor in dissolving model cholesterol gallstones. Model cholesterol gallstones could be more effectively dissolved by increasing the steric interactive potential energy of side chains and ensuring that the hydrophilic–lipophilic properties of MP–CDCA are within an appropriate range. The micellar dissolution rates of model cholesterol gallstones by MP20–CDCA were significantly faster than by the other conjugates.

Selective synthesis of amphiphilic hydroxyalkylethers of disaccharides over solid basic catalysts: Influence of the superficial hydrophilic–lipophilic balance of the catalyst

The direct etherification of three disaccharidic polyols, sucrose, trehalose and isomalt ®, with 1,2-epoxydodecane was studied. The catalytic activity of various solid basic catalysts, differing by their superficial hydrophilic–lipophilic properties, was investigated. Disaccharide hydroxyalkylethers yields greater than 90% were obtained in a DMSO–water mixture in the presence of the recoverable PS–NOH solid catalyst. The regioselectivity of the reaction was fully investigated by HPLC and NMR.

RETRACTED: Preparation and thermal properties of form-stable paraffin phase change material encapsulation

Form-stable paraffin phase change materials (PCMs), in which the paraffin as a latent heat storage material and the polyolefins as a supporting material, have to be encapsulated because of the paraffin leakage and lipophilicity. A novel microencapsulated PCM in which form-stable paraffin is encapsulated into inorganic silica gel polymer is prepared successfully by in situ polymerization. A differential scanning calorimeter (DSC) is used to measure the thermal properties of the PCM. Moreover, the Washburn equation associated with the wetting properties of powder materials, is used to test the hydrophilic-lipophilic properties of PCM. The results indicate that the optimum microencapsulated PCM is endowed with good hydrophilicity, and its specific enthalpy maintains 123.78 J g -1 .

The influence of surfactant mixing ratio on nano-emulsion formation by the pit method

The formation of O/W nano-emulsions by the PIT emulsification method in water/mixed nonionic surfactant/oil systems has been studied. The hydrophilic–lipophilic properties of the surfactant were varied by mixing polyoxyethylene 4-lauryl ether ( C ¯ 12 E ¯ 4 ) and polyoxyethylene 6-lauryl ether ( C ¯ 12 E ¯ 6 ). Emulsification was performed in samples with constant oil concentration (20 wt%) by fast cooling from the corresponding HLB temperature to 25 °C. Nano-emulsions with droplet radius 60–70 nm and 25–30 nm were obtained at total surfactant concentrations of 4 and 8 wt%, respectively. Moreover, droplet size remained practically unchanged, independent of the surfactant mixing ratio, X C 12E 6 . At 4 wt% surfactant concentration, the polydispersity and instability of nano-emulsions increased with the increase in X C 12E 6 . However, at 8 wt% surfactant concentration, nano-emulsions with low polydispersity and high stability were obtained in a wide range of surfactant mixing ratios. Phase behavior studies showed that at 4 wt% surfactant concentration, three-liquid phases (W + D + O) coexist at the starting emulsification temperature. Furthermore, the excess oil phase with respect to the microemulsion D-phase increases with the increase in X C 12E 6 , which could explain the increase in instability. At 8 wt% surfactant concentration, a microemulsion D-phase is present when emulsification starts. The low droplet size and polydispersity and higher stability of these nano-emulsions have been attributed, in addition to the increase in the surface or interfacial activity, to the spontaneous emulsification produced in the microemulsion D-phase.