Spontaneous Emulsification Research Articles

Spontaneous Emulsification of Triolein Induced by Mixed Micellar Solutions of Sodium Polyoxyethylene Alkyl Ether Sulfate and Dodecyldimethyl Amine Oxide.

A new mechanism of spontaneous emulsification without any salts or co-solvents is described, and is related to the dilatational behavior. Spontaneous emulsification can reduce the time required to remove oily soils from hard surfaces and enhance the detergency, because this type of emulsification requires no external mechanical work. In this paper, we focused on triolein, the main component of food oils and human sebum soil, and tried to induce spontaneous emulsification by using mixed micellar solutions of sodium polyoxyethylene alkyl ether sulfate and N, N-dimethyldodecylamine oxide (AES/DDAO). We characterized the dilatation of the oil/water interface using dynamic interfacial tension and elasticity measurements. This study confirmed that the degree of spontaneous emulsification can be enhanced by controlling the molar ratio of DDAO to AES. This enhancement can be attributed to an increased rate of decrease in the dynamic interfacial tension (i.e., a decreased interface dilatational elasticity), allowing for much greater suppression of the Marangoni effect. Further, we determined that one of the reasons for the decrease in the interface dilatational elasticity is the increasing number of micelles near the oil drop interface, which results from a decrease in the electrostatic repulsion between the micelles and the drop interface. Therefore, controlling the molar ratio of a mixed anionic/amphoteric surfactant solution is an effective way to induce spontaneous emulsification in the absence of salts or co-solvents.

Microfluidic protein crystallisation controlled using spontaneous emulsification

Microdroplet-based protein crystallisation using spontaneous emulsification is proposed and demonstrated. The dependency of crystal number in a single microdroplet on the surfactant concentration is discussed.

Lignin supracolloids synthesized from (W/O) microemulsions: use in the interfacial stabilization of Pickering systems and organic carriers for silver metal.

Taking advantage of the aromatic and cross-linking tendency of lignin macromolecules extracted from plants, we present a novel method for their assembly into supracolloidal structures. Specifically, spherical particles with controllable size (∼90 nm to 1 μm) were obtained from water-in-oil (W/O) microemulsions formulated with a mixture of nonionic surfactants and a colloidal dispersion of a low molecular weight alkali lignin. After spontaneous emulsification, the internal lignin-rich phase was cross-linked to produce the solid particles that could be easily separated by removal of the organic, continuous phase. The efficiency of the fractionated lignin particles to stabilize hexadecane-in-water Pickering emulsions was demonstrated and their properties were compared against those obtained by using traditional inorganic particles. The effect of the particle size of lignin on the emulsion structure is discussed. As a proof of concept we further introduce the use of related emulsions to enable in situ reduction of silver and loading of silver nanoparticles in lignin carriers.

Formation of thermally reversible optically transparent emulsion-based delivery systems using spontaneous emulsification.

Transparent emulsion-based delivery systems suitable for encapsulating lipophilic bioactive agents can be fabricated using low-energy spontaneous emulsification methods. These emulsions are typically fabricated from non-ionic surfactants whose hydrophilic head groups are susceptible to dehydration upon heating. This phenomenon may promote emulsion instability due to enhanced droplet coalescence at elevated temperatures. Conversely, the same phenomenon can be used to fabricate optically transparent emulsions through the phase inversion temperature (PIT) method. The purpose of the current study was to examine the influence of oil phase composition and surfactant-to-oil ratio on the thermal behavior of surfactant-oil-water systems containing limonene, medium chain triglycerides (MCT), and Tween 60. Various types of thermal behavior (turbidity versus temperature profiles) were exhibited by these systems depending on their initial composition. For certain compositions, thermoreversible emulsions could be formed that were opaque at high temperatures but transparent at ambient temperatures. These systems may be particularly suitable for the encapsulation of bioactive agents in applications where optical clarity is important.

Nanoemulsion formation and characterization by spontaneous emulsification: Investigation of its antibacterial effects on Listeria monocytogenes

Nanoemulsion formation and characterization by spontaneous emulsification: Investigation of its antibacterial effects on Listeria monocytogenes

Uphill diffusion in multicomponent mixtures

Molecular diffusion is an omnipresent phenomena that is important in a wide variety of contexts in chemical, physical, and biological processes. In the majority of cases, the diffusion process can be adequately described by Fick's law that postulates a linear relationship between the flux of any species and its own concentration gradient. Most commonly, a component diffuses down the concentration gradient. The major objective of this review is to highlight a very wide variety of situations that cause the uphill transport of one constituent in the mixture. Uphill diffusion may occur in multicomponent mixtures in which the diffusion flux of any species is strongly coupled to that of its partner species. Such coupling effects often arise from strong thermodynamic non-idealities. For a quantitative description we need to use chemical potential gradients as driving forces. The transport of ionic species in aqueous solutions is coupled with its partner ions because of the electro-neutrality constraints; such constraints may accelerate or decelerate a specific ion. When uphill diffusion occurs, we observe transient overshoots during equilibration; the equilibration process follows serpentine trajectories in composition space. For mixtures of liquids, alloys, ceramics and glasses the serpentine trajectories could cause entry into meta-stable composition zones; such entry could result in phenomena such as spinodal decomposition, spontaneous emulsification, and the Ouzo effect. For distillation of multicomponent mixtures that form azeotropes, uphill diffusion may allow crossing of distillation boundaries that are normally forbidden. For mixture separations with microporous adsorbents, uphill diffusion can cause supra-equilibrium loadings to be achieved during transient uptake within crystals; this allows the possibility of over-riding adsorption equilibrium for achieving difficult separations.

Serpentine diffusion trajectories and the Ouzo effect in partially miscible ternary liquid mixtures.

This work investigates the transient equilibration process when partially miscible ternary liquid mixtures of two different compositions are brought into contact with each other. Diffusional coupling effects are shown to become increasingly significant as the mixture compositions approach the meta-stable regions of the phase equilibrium diagrams. The proper modelling of coupled diffusion phenomena requires the use of a Fick diffusivity matrix [D], with inclusion of non-zero off-diagonal elements. The primary objective of this article is to develop a simple, robust, procedure for the estimation of the matrix [D], using the Maxwell-Stefan (M-S) formulation as a convenient starting point. In the developed simplified approach, the Fick diffusivity matrix [D] is expressed as the product of a scalar diffusivity and the matrix of thermodynamic correction factors [Γ]. By detailed examination of experimental data for the matrix [D] in a wide variety of ternary mixtures, it is deduced that the major contribution of diffusional coupling arises from the contributions of non-ideal solution thermodynamics, quantified by the matrix of thermodynamic correction factors [Γ]. An important consequence of strong thermodynamic coupling is that equilibration trajectories are serpentine in shape and may exhibit incursions into meta-stable zones opening up the possibility of spontaneous emulsification and the Ouzo effect. If diffusional coupling effects are ignored, the equilibration trajectory is linear in composition space. For a wide variety of partially miscible ternary mixtures, it is demonstrated that the corresponding linear equilibration trajectories do not anticipate the possibility of emulsification.

Development, evaluation, and optimization of flurbiprofen nanoemulsions gel using quality by design concept

The objective of this study was to formulate topical gel loaded nanoemulsions containing flurbiprofen using volatile oil. The gel released the drug at a controlled rate to the targeted site. Flurbiprofen (log P = 4.09) in generally used for transdermal treatment of rheumatoid arthritis and osteoarthritis. Selection of the oil phase, surfactant, and cosurfactant was done by individual screening method with the aid of pseudo‐ternary phase study. International Conference on Harmonisation Q8 guidelines was applied using 32 factorial designs coupled with response surface methodology. The formulations were prepared by using spontaneous emulsification method. The selected formulation from various statistical and other studies was investigated. It was found that selected formulation showed an optimum in‐vitro data. Later the optimized formulation obtained within the tentative design space was incorporated in the gel and compared with the marketed formulation.The result suggested the optimized formulation with good potential for transdermal delivery of the drug than the marketed formulations. Key words: Design space, flurbiprofen, in‐vitro diffusion, nanoemulsions, transdermal drug delivery

Influence of additives on the structure of surfactant-free microemulsions.

We study the addition of electrolytes to surfactant-free microemulsions in the domain where polydisperse pre-Ouzo aggregates are present. As in previous studies, the microemulsion is the ternary system water/ethanol/1-octanol, where ethanol acts as co-solvent. Addition of electrolytes modifies the static X-ray and neutron scattering, and dynamic light scattering patterns, as well as the position of the miscibility gap, where spontaneous emulsification occurs upon dilution with water. All observations can be rationalized considering that electrolytes are either "salting out" the ethanol, which is the main component of the interface stabilizing the aggregates, or producing charge separation via the antagonistic ion effect discovered by Onuki et al. Amphiphilic electrolytes, such as sodium dodecylsulfate or sodium dietheylhexylphosphate, induce a gradual transition towards monodisperse ionic micelles with their characteristic broad scattering "peak". In these micelles the ethanol plays then the role of a cosurfactant. Dynamic light scattering can only be understood by combination of fluctuations of aggregate concentration due to the vicinity of a critical point and in-out fluctuations of ethanol.

Food-grade nanoemulsion filled hydrogels formed by spontaneous emulsification and gelation: Optical properties, rheology, and stability

Nanoemulsions may be used as delivery systems for lipophilic bioactive components in foods and beverages, such as oil-soluble vitamins, nutraceuticals, flavors, and antimicrobials. In this study, we examined the possibility of incorporating nanoemulsions into clear gelatin hydrogels to form optically translucent hydrogels. The effect of preparation and storage conditions on the formation and stability of nanoemulsion-filled gelatin hydrogels was studied. Nanoemulsions were produced using the spontaneous emulsification (SE) method, which simply involves addition of an organic phase (oil + surfactant) to an aqueous phase. Droplet size decreased and optical clarity increased when the SE method was performed at an elevated temperature (60 °C) rather than at ambient temperature (20 °C). Translucent filled hydrogels could be formed by incorporating the nanoemulsions into gelatin gels. The optical and rheological properties of a model gelatin gel and a commercial gelatin dessert did not change appreciably after the nanoemulsion droplets (1%) were incorporated. This approach may therefore be useful for the incorporation of various types of lipophilic bioactive agents into functional food gels.

Spontaneous Emulsification of a Metal Drop Immersed in Slag Due to Dephosphorization: Surface Area Quantification

When a chemical reaction occurs between two immiscible liquids, mass transfer is continuously taking place at the liquid–liquid interface. Several studies have shown that if the species being exchanged between the two liquids are surface-active, a very pronounced decrease in interfacial tension can occur which can lead to a phenomenon called spontaneous emulsification. In steelmaking, this behavior has been observed for several reactions that involve the transfer of impurities from molten steel to a molten-oxide slag but little quantification has been made. This work focuses on spontaneous emulsification due to the dephosphorization of a Fe-P drop immersed in a basic oxygen furnace type slag. An Au-image furnace attached to a confocal scanning laser microscope was used to rapidly heat and cool the samples at different times, and X-ray computerized tomography was used to perform the surface area calculations of the samples where the slag/steel reaction was allowed to occur for distinct times. The results show that the surface area of the metal drop rapidly increases by over one order of magnitude during the first 60 seconds of the reaction while the chemical reaction is occurring at a fast rate. Once the reaction slows down, approximately after 60 seconds, the droplets start to coalesce back together minimizing the surface area and returning to a geometry close to its equilibrium shape.

NANOEMULSIFIKASI SPONTAN EKSTRAK JINTAN HITAM DAN KARAKTERISTIK PRODUK ENKAPSULASINYA [Spontaneous Nanoemulsification of Black Cumin Extract and the Characteristics of the Encapsulation Product

Low energy nano technology research with black cumin materials is still limited. Encapsulation of black cumin extract nanoemulsion has been developed and the products have been characterized. The aims of this study are determining the extraction method of black cumin seed, formulating black cumin extract nanoemulsion by spontaneous emulsification technique, and encapsulating black cumin extract nanoemulsion. Three stages of experiments were done in this study, i.e. extraction, nanoemulsification and encapsulation. First, extraction was done using maceration and reflux method and the best result was sent to the nanoemulsification process. Second, a spontaneous nanoemulsification was performed involving organic phase (black cumin extracts were dissolved in ethanol 70%), and water phase (Tween 80 solution with three different percentages 1, 2 and 3% w/w) to produced the best nanoemulsion. Third, the best nanoemulsion based on size, homogeneity, and stability of the particles, was encapsulated using two different encapsulating material compositions, i.e. maltodextrin (100%) and combination of maltodextrin and soy protein isolate at a ratio 80 and 20 (w/w). The results showed that three-hour reflux method produced better black cumin extract properties than that of maceration method. A percentage of 3% surfactant gave a stable nanoemulsion with average droplet size of 10.93 nm. Reconstitution of nanoemulsion encapsulation product that has more spherical globules, indicated efficient encapsulation process. The use of combination of maltodextrin and soy protein isolate provided a better preservation of phenolic content and antioxidant capacity as compared to the use of maltodextrin alone.

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles (PLGA-Cur NPs) through a modified spontaneous emulsification solvent diffusion (modified-SESD) method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield (58.9%), drug loading (11.0% (w/w)) and encapsulation efficiency (33.5%), and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.

Development And Characterization of Inhaled Chitosan Nanoparticles Loaded with Isoniazid

The objective of our study is to load first line anti-tubercular drug, Isoniazid in chitosan Nanoparticles in order to enhance bioavailability and to reduce dose frequency. The chitosan nanoparticles containing the drug Isoniazid were prepared by the method of spontaneous emulsification. Chitosan gel containing drug is cross linked with Glutaraldehyde and nanoparticle suspension obtained was centrifuged at 5000 rpm. It was then evaluated for Drug loading, swelling index, Mucoadhesive force, Zeta potential, DLS studies, DSC studies, SEM studies, In vitro Drug release, Pharmacokinetic Studies and Stability studies.Formulation 1(F1) shows maximum Drug Loading, Swelling index and mucoadhesive force. The positive zeta value was obtained for all formulations due to positive charge of polymer used in preparation of dispersion. The DLS plot of Formulations shows that Average particle diameter are in the range of 661.8-823.8nm. The SEM study revealed that the micrographs of cross linked chitosan nanoparticles have smooth surface. The thermogram of the formulations showed the shifting of endotherm. This indicates the possible change in the release kinetics and bioavailability of the drug. In vitro drug releases was found to be maximum for formulation F6. Pharmacokinetic evaluation shows all the formulation shows first order rate release profile and release mechanism from nanoparticles is diffusion controlled. Stability studies indicated that the developed chitosan nanoparticles are physically and chemically stable and retain their pharmaceutical properties at various environmental conditions over a period of 3 months.

Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml−1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of −35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

Effect of salts on formation and stability of vitamin E-enriched mini-emulsions produced by spontaneous emulsification.

Emulsion-based delivery systems are being utilized to incorporate lipophilic bioactive components into various food, personal care, and pharmaceutical products. This study examined the influence of inorganic salts (NaCl and CaCl2) on the formation, stability, and properties of vitamin E-enriched emulsions prepared by spontaneous emulsification. These emulsions were simply formed by titration of a mixture of vitamin E acetate (VE), carrier oil (MCT), and nonionic surfactant (Tween 80) into an aqueous salt solution with continuous stirring. Salt type and concentration (0-1 N NaCl or 0-0.5 N CaCl2) did not have a significant influence on the initial droplet size of the emulsions. On the other hand, the isothermal and thermal stabilities of the emulsions depended strongly on salt levels. The cloud point of the emulsions decreased with increasing salt concentration, which was attributed to accelerated droplet coalescence in the presence of salts. Dilution (2-6 times) of the emulsions with water appreciably improved their thermal stability by increasing their cloud point, which was mainly attributed to the decrease in aqueous phase salt levels. The isothermal storage stability of the emulsions also depended on salt concentration; however, increasing the salt concentration decreased the rate of droplet growth, which was the opposite of its effect on thermal stability. Potential physicochemical mechanisms for these effects are discussed in terms of the influence of salt ions on van der Waals and electrostatic interactions. This study provides important information about the effect of inorganic salts on the formation and stability of vitamin E emulsions suitable for use in food, personal care, and pharmaceutical products.

Stability of monodisperse clove oil droplets prepared by microchannel emulsification

Monodisperse clove oil droplets in the form of oil-in-water (O/W) emulsions stabilized by 0.1% and 0.5% w/w sodium dodecyl sulphate (SDS) were successfully produced by microchannel (MC) emulsification using a 15 × 15 mm2 MC array plate with 100 parallel MCs fabricated on each side of the plate. The channels have 71 μm length, 8.2 μm width, and 4 μm depth with hydraulic diameter of 4.2 μm. The terraces have the same depth size as the channels with 29.1 μm length. The average droplet diameter was 17 μm with a coefficient of variation around 3%. The droplet size deviated from monodispersity over time and it depended on the droplet configuration on MC array plate. The droplet size became polydisperse within 2 h when the droplets were surrounded by plenty of continuous phase. A higher SDS concentration resulted in more polydisperse droplet size over time. This instability is proposed as the result of diffusion-driven mechanism, spontaneous emulsification, and reversed micelle formation. Instability could be suppressed by saturating both continuous and dispersed phases prior to emulsification. This step may prevent the diffusion that takes place once the oil–water interface is formed.

Spontaneous emulsification of nifedipine-loaded self-nanoemulsifying drug delivery system.

Self-nanoemulsifying drug delivery system (SNEDDS) can be used to improve dissolution of poorly water-soluble drugs. The objective of this study was to prepare SNEDDS by using ternary phase diagram and investigate their spontaneous emulsifying property, dissolution of nifedipine (NDP), as well as the pharmacokinetic profile of selected SNEDDS formulation. The results showed that the composition of the SNEDDS was a great importance for the spontaneous emulsification. Based on ternary phase diagram, the region giving the SNEDDS with emulsion droplet size of less than 300 nm after diluting in aqueous medium was selected for further formulation. The small-angle X-ray scattering curves showed no sharp peak after dilution at different percentages of water, suggesting non-ordered structure. The system was found to be robust in different dilution volumes; the droplet size was in nanometer range. In vitro dissolution study showed remarkable increase in dissolution of NDP from SNEDDS formulations compared with NDP powders. The pharmacokinetic study of selected SNEDDS formulation in male Wistar rats revealed the improved maximum concentration and area under the curve. Our results proposed that the developed SNEDDS formations could be promising to improve the dissolution and oral bioavailability of NDP.

Fabrication of spontaneous emulsifying powders for improved dissolution of poorly water-soluble drugs

The aim of the present study was to fabricate spontaneous emulsifying powders (SEP) for improving dissolution of poorly water-soluble drugs for oral drug delivery. The effect of drugs with different lipophilicity (logP), that is, nifedipine, felodipine, manidipine, and itraconazole on crystalline properties and dissolution profiles of SEP was also examined. The liquid spontaneous emulsifying formulation (SEF), composing of polyoxyl 35 castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether at a ratio of 1:1:8, was solidified with three different solid carriers, namely, fumed silica, porous silicon dioxide and porous calcium silicate (at 20%–50%). Porous calcium silicate at a concentration of 50% produced an excellent solid SEP formulation with the highest drug dissolution. The SEP formulations were free flowing with similar characteristics as that of liquid SEF. The differential scanning calorimetry and powder X-ray diffraction studies revealed the transformation of crystalline drugs (in pure drugs) to amorphous drugs (in the SEP formulations). This was further confirmed by scanning electron microscopy. Also, SEP containing 50% porous calcium silicate significantly improved the dissolution rate of all drugs tested due to the fast spontaneous emulsion formation and the decreased droplet size. Accordingly, this novel SEP formulation is the versatile and useful formulation that could be used to enhance the oral bioavailability of drugs by improving the dissolution of poorly water-soluble drugs.

Microemulsion system for topical delivery of thai mango seed kernel extract: development, physicochemical characterisation and ex vivo skin permeation studies.

A microemulsion system containing Thai mango seed kernel extract (MSKE, cultivar “Fahlun”) was developed and characterised for the purpose of topical skin delivery. The MSKE-loaded microemulsions were prepared by using the spontaneous emulsification method. Isopropyl myristate (IPM) was selected as the oil phase. A polyoxyethylene sorbitan monooleate and sorbitan monododecanoate (1:1, w/w) system was used as the surfactant phase; an aqueous mixture of different cosurfactants (absolute ethanol, 96.3% v/v ethanol, 1-propanol, 2-propanol or 1,2-propanediol) at a weight ratio of 1:1 was used as the aqueous phase. Among the cosurfactants studied, the 1-propanol aqueous mixture had the largest microemulsion region (48.93%) in the pseudo-ternary phase diagram. Microemulsions containing 1% MSKE demonstrated good physicochemical stability during a six-month study period at 25 ± 2 °C/60% ± 5% RH. The ex vivo skin permeation study demonstrated that the microemulsions exhibited a potent skin enhancement effect allowing MSKE to penetrate skin layers up to 60-fold higher compared with the control. Neither skin irritation nor skin corrosion was observed in ex vivo studies. The present study revealed that IPM-based microemulsion systems may be promising carriers to enhance skin penetration and delivering MSKE for topical treatment.