Conventional Emulsification Research Articles

Droplet Microfluidic Devices: Working Principles, Fabrication Methods, and Scale-Up Applications.

Compared with the conventional emulsification method, droplets generated within microfluidic devices exhibit distinct advantages such as precise control of fluids, exceptional monodispersity, uniform morphology, flexible manipulation, and narrow size distribution. These inherent benefits, including intrinsic safety, excellent heat and mass transfer capabilities, and large surface-to-volume ratio, have led to the widespread applications of droplet-based microfluidics across diverse fields, encompassing chemical engineering, particle synthesis, biological detection, diagnostics, emulsion preparation, and pharmaceuticals. However, despite its promising potential for versatile applications, the practical utilization of this technology in commercial and industrial is extremely limited to the inherently low production rates achievable within a single microchannel. Over the past two decades, droplet-based microfluidics has evolved significantly, considerably transitioning from a proof-of-concept stage to industrialization. And now there is a growing trend towards translating academic research into commercial and industrial applications, primarily driven by the burgeoning demands of various fields. This paper comprehensively reviews recent advancements in droplet-based microfluidics, covering the fundamental working principles and the critical aspect of scale-up integration from working principles to scale-up integration. Based on the existing scale-up strategies, the paper also outlines the future research directions, identifies the potential opportunities, and addresses the typical unsolved challenges.

Cold Emulsified Nanoemulsion: Enhancing Delivery and Stability of Thermolabile Acyclovir

Acyclovir is an acyclic purine nucleoside widely used as an antiviral agent with good topical efficacy. Acyclovir is a thermolabile drug, making it challenging to formulate a stable and effective emulsion via a conventional emulsification process. This study aims to develop, optimize, and characterize the nanoemulsion of thermolabile drug acyclovir, manufactured by adopting a cold emulsification process and compare the physicochemical properties and diffusion pattern with a leading marketed formulation. Diffusion studies were conducted using Franz diffusion cells. The optimized formulation was subjected to quantitative estimation of acyclovir, impurity profiling, viscosity, pH, vesicle size, shape, and polydispersibility index (PDI). In the current study, the particle size of the nanoemulsion varies from 66.25 to 244.40 nm, and the zeta potential revealed a high negative surface charge on the particles. Transmission electron microscopy images revealed spherical-shaped, non-aggregated, and discrete globules. The in-vitro diffusion study of acyclovir nanoemulsion showed enhanced penetration efficacy than the conventional emulsion. All these observations signified that the cold emulsification process for manufacturing nanoemulsion is appropriate for thermolabile and pH-sensitive drugs. The study demonstrates enhanced stability and efficacy of optimized acyclovir nanoemulsion through cold emulsification.

Linking processing to formulation in dynamic membranes of tunable pore size for lemon oil emulsions

Lemon oil is widely used for food flavoring purposes, but due to its low water solubility and tendency to oxidation, requires encapsulation in oil-in-water (O/W) emulsions. Therefore, this study assesses the use of two natural biopolymers and a tailor-made one to encapsulate lemon oil with a dynamic membrane of tunable pore size (DMTS). This emulsification system, consisting of an outer bed layer of silica beads sitting upon a metal microporous metallic membrane, overcomes the limitations of conventional emulsification membranes, such as low throughput, complex cleaning before reuse, fixed membrane thickness and pore size, and significative protein fouling. The effects of the DMTS characteristics on the droplet size distribution and emulsion productivity were studied. The results demonstrate that mono-dispersed emulsions can be obtained using dynamic membranes for all the biopolymers studied and the productivity can reach 1000 m3 m−2h−1 pointing out the suitability of this system for scale-up.

PLGA nanoparticles enhanced cardio-protection of scutellarin and paeoniflorin against isoproterenol-induced myocardial ischemia in rats

This study aims to examine the impact of the microfluidic preparation process on the quality of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-delivered with scutellarin (SCU) and paeoniflorin (PAE) in comparison to a conventional emulsification method and to evaluatethe potential cardio-protective effect of SCU-PAE PLGA NPs produced through emulsification method. As compared with microfluidics, the nanoparticles prepared by emulsification method exhibited a smaller size, higher encapsulation efficiency, higher drug loading and lower viscosity for injection. Subsequently, a rat myocardial ischemia (MI) was established using male Sprague-Dawley (SD) rats (250 ± 20 g) subcutaneously injected with 85 mg/kg isoproterenol (ISO) for two consecutive days. The pharmacokinetic findings demonstrated that our SCU-PAE PLGA NPs exhibited prolonged blood circulation time in MI rats, leading to increased levels of SCU and PAE in the heart. This resulted in significant improvements in electrocardiogram and cardiac index, as well as reduced serum levels of CK, LDH, AST. Histopathological analysis using H&E and TUNEL staining provided further evidence of improved cardiac function and decreased apoptosis. Additionally, experiments measuring SOD, MDA, GSH, NO, TNF-α and IL-6 levels indicated that SCU-PAE PLGA NPs may effectively treat MI through oxidative stress and inflammatory pathways, thereby establishing it as a promising therapeutic intervention.

Ouzo Effect Examined at the Nanoscale via Direct Observation of Droplet Nucleation and Morphology.

Herein, we present the direct observation via liquid-phase transmission electron microscopy (LPTEM) of the nucleation and growth pathways of structures formed by the so-called "ouzo effect", which is a classic example of surfactant-free, spontaneous emulsification. Such liquid-liquid phase separation occurs in ternary systems with an appropriate cosolvent such that the addition of the third component extracts the cosolvent and makes the other component insoluble. Such droplets are homogeneously sized, stable, and require minimal energy to disperse compared to conventional emulsification methods. Thus, ouzo precipitation processes are an attractive, straightforward, and energy-efficient technique for preparing dispersions, especially those made on an industrial scale. While this process and the resulting emulsions have been studied by numerous indirect techniques (e.g., X-ray and light scattering), direct observation of such structures and their formation at the nanoscale has remained elusive. Here, we employed the nascent technique of LPTEM to simultaneously evaluate droplet growth and nanostructure. Observation of such emulsification and its rate dependence is a promising indication that similar LPTEM methodologies may be used to investigate emulsion formation and kinetics.

Electrospinning with Droplet Generators: A Method for Continuous Electrospinning of Emulsion Fibers

Emulsion electrospinning is a promising method for creating fibrous vehicles for delivery of drugs and bioactive compounds for the medical and food industries. Droplet microfluidics is a potent way of continuously generating controllable emulsion droplets. The incorporation of a droplet generator in an electrospinning setup for continuous electrospinning of emulsion fibers has been investigated. The influence of a droplet generator on the morphology of emulsion fibers has been established through electrospinning of emulsions of grapeseed oil in PVA and gelatine. The droplet generator was found to have no influence on the morphology of fibers. Conventional emulsification methods and droplet generator emulsification has been used to investigate the influence of emulsion droplet sizes on the morphology of emulsion fibers. Increasing the emulsion droplet size was found to create in-fiber droplets with diameters larger than the fiber diameter. The size of the in-fiber droplets was found to be dependent on both material and emulsion size.

A collaborative emulsification system capable of forming stable small droplets of oil-in-water emulsions for enhancing heavy oil recovery

Water flooding for heavy oil development has a relatively low recovery effect. Emulsification system flooding is a very effective method for enhanced heavy oil recovery after water flooding. However, the sizes of oil-in-water (O/W) emulsion droplets formed by conventional emulsification systems and heavy oil are relatively large. Large droplet emulsions result in higher additional resistance when flowing in the porous media of the reservoir, which restricts the development effect on heavy oil recovery. In this study, a primary alcohol ethoxylate (AEO12) + sodium dodecyl sulfate (SDS) + alkali (NaOH) mixed collaborative emulsification (CE) system was developed and its formula was optimized. The optimal collaborative emulsification system formula is primary alcohol ethoxylate (0.25%) + sodium dodecyl sulfate (0.25%) + NaOH (0.05%). Through interfacial tension measurements, microemulsion state observations, emulsion particle size distribution tests, multiple light scattering, and fluidity experiments in simulated reservoir porous media, the oil-in-water emulsion stability and the mechanism of collaborative emulsification for improving heavy oil recovery were studied. Compared with the surfactant, the collaborative emulsification system can be more closely arranged at the heavy oil–water interface, so that the system can significantly reduce interfacial tension (IFT) (0.008 mN/m), formed a more stable and smaller oil-in-water emulsion (0.2 μm). It can greatly reduce the influence of additional resistance on its fluidity in reservoir porous media, and still has an excellent viscosity reduction rate at high temperatures (99.50% at 20 °C; 88.55% at 100 °C). Finally, through microscopic visualization experiments, it was shown that the collaborative emulsification system has an excellent ability to improve the sweep coefficient, and the residual heavy oil can be emulsified into oil droplets that are much smaller than pore throats. The developed collaborative emulsification system has excellent potential for enhancing heavy oil recovery after water/hot water flooding.

Microfluidics as a tool to assess and induce emulsion destabilization.

Microfluidic technology enables judicious control of the process parameters on a small length scale, which in turn allows speeding up the destabilization of emulsion droplets interface in microfluidic devices. In this light, microfluidic channels can be used as an efficient tool to assess emulsion stability and to observe the behavior of the droplets immediately after their formation, enabling to determine whether or not they are prone to re-coalescence. Observation of the droplets after emulsifier adsorption also allows the investigation of emulsion stability over time. Both evaluations would contribute to determine emulsion stability aiming at specific applications in food and pharmaceutical industries. Furthermore, emulsion coalescence can also be performed under extremely controlled conditions within the microfluidic devices in order to explore emulsion droplets as micro-reactors (for regulated biological and chemical assays). Such microfluidic procedures can be performed either in confined environments or under dynamic flow conditions. Under confined environments, droplets are observed in fixed positions simulating different environmental conditions. On the other hand, with the scrutiny of emulsions under dynamic flow processes, it is possible to determine the behavior of the droplets when subjected to shear forces, comparable to those experienced in conventional emulsification techniques or even in pumping operations. Given the above, this paper reviews different microfluidic techniques (such as changing channel geometry or wettability) hitherto used to destabilize emulsions, mainly focusing on the specificities of each study, whether the droplets are destabilized in confined or dynamic flow processes. Thereby, by going deeper into this review, readers will be able to identify different strategies for emulsion destabilization (in order to understand stabilizing mechanisms or even to apply these droplets as micro-reactors), as this paper shows the particularities of the most recent studies and elucidates the current state-of-the-art of this microfluidic-related application.

Fuel properties of water emulsion fuel prepared using porous membrane method for low pollutant engine at various temperatures

Due to strengthened emission regulations, it is difficult to continuously use fuels for internal combustion engines such as gasoline and diesel. Emulsion fuel is a technology that can simultaneously reduce NOx and PM, the biggest problems of existing compression ignition engines. Since conventional emulsification technology involve various limitations. An emulsion fuel was prepared using a porous membrane emulsification method that maximizes stability and production efficiency. The kinematic viscosity of the emulsion fuel according to the water content and temperature was evaluated. And various basic properties (sulfur content, flash point, kinematic viscosity, density, ultimate analysis, net calorific value, and gross calorific value) of the prepared fuel was requested from an external institute for validation. The density and kinematic viscosity increased as the water content used in the manufacture of emulsion fuel increased, and the density and kinematic viscosity decreased as the temperature of the fuel increased. Based on the measurement results, an empirical equation according to temperature and water content was proposed. The error rate of the derived empirical equation is mostly less than 5%. And in most cases, the adjusted R-square value exceeded 0.95, so the proposed empirical equation was considered reliable. The proposed empirical equation can be utilized for obtaining the basic data for the emulsion fuel or water blended fuel.

Early film formation in protein-stabilised emulsions: Insights from a microfluidic approach

In conventional emulsification devices, interface formation and stabilisation occur within milliseconds. Protein network formation at liquid-liquid interfaces starts at time scales similar to those of droplet formation in conventional emulsification devices (i.e., in milliseconds). Classical methods, like drop tensiometry, do not allow measurements at these time scales. Using a tailor-made microchip, we probed droplet deformation to study the interfacial rheological properties of droplets, within time scales ranging from 0.16 to 1 s. We further investigated the coalescence stability of droplets at the same time scales. Whey protein isolate (WPI), pea protein isolate (PPI), or their blends were used as emulsifiers at 0.01–1 g/L. The rheological properties of the protein-interfaces showed that early network formation takes place (<1 s). WPI-stabilised interfaces were mechanically stronger compared to PPI-stabilised interfaces, and WPI-stabilised droplets were much less prone to coalescence than their PPI counterparts. Although the blend-stabilised films showed high interconnectivity, this did not prevent droplet coalescence, probably due to structural heterogeneity. The insights obtained with the tailor-made microfluidic devices help to capture effects at short time scales and are relevant to unravel phenomena occurring in large scale processing.

Fundamental Differences in Emulsification Principle between Three-phase Emulsification and Conventional Methods.

The present study investigates the principle difference between three-phase emulsification and conventional emulsification methods (surfactant emulsification and the Pickering method). Conventional emulsification methods depend on intensive factors such as interfacial tension and wetting. In the proposed three-phase emulsification, soft hydrophilic nanoparticles adhere to the oil-water interface due to the van der Waals attraction and stabilize the emulsion. Therefore, it can be said that three-phase emulsification is "extensive emulsification" based on the mass of the hydrophilic nanoparticles and oil droplets. Extensive emulsification is irreversible because the van der Waals attraction acts between the particles unless the mass of the soft hydrophilic nanoparticles and oil droplets changes. The differences between three-phase emulsification and conventional emulsification methods were experimentally verified by comparing the difference in the stability of the emulsions resulting from the change in intensive factors, where the internal phase oil transitioned from solid to liquid. The emulsions prepared using the surfactant and Pickering methods were separated into oil and water by the solid-liquid phase transition of hexadecane in the internal oil phase. However, the emulsion prepared using three-phase emulsification maintained its emulsified state without any oil-water separation even when the internal oil phase underwent solid-liquid phase transition. From the results obtained, it can be concluded that three-phase emulsification is an irreversible method because its mechanism is based on extensive factors. Furthermore, this irreversible method allows the emulsification of various oils that cannot be emulsified by conventional methods, and it is also possible to directly mix emulsions prepared with different oils. The authors also call attention to the possibility of improving emulsion characters and new developments in emulsion science.

Low-energy high-throughput emulsification with nickel micro-sieves for essential oils encapsulation

Lemon oil is widely used in food manufacturing, however its tendency to oxidize and its lipophilic character requires its encapsulation, either in emulsions or in microcapsules. Conventional emulsification technologies are highly energy intensive, damaging shear and heat sensitive products. This work assesses a high-throughput low-energy premix emulsification system based on nickel micro-sieves to produce food grade lemon oil-water emulsions. Successful encapsulation is achieved when both the lemon oil fraction is about 5% and the ratio between the size of the coarse emulsion and the hydraulic diameter of the micro-sieves (dratio) is 1 or lower. These conditions result in high fluxes (400–800 m3 m−2 h−1 at 450 kPa) and emulsions of about 0.5 μm after 5 emulsification cycles. Droplet break-up mechanisms differ in the first emulsification cycle depending on the pore size and geometry of the micro-sieve.

Polysorbate 80 coated crosslinked chitosan nanoparticles of ropinirole hydrochloride for brain targeting

Targeting ropinirole hydrochloride (R-HCl) to brain in effective amount may be a breakthrough in the treatment of Parkinson's disease due to its extensive first-pass metabolism in stomach after oral administration. The aim of the present investigation was to increase the brain uptake of R-HCl through chitosan nanoparticles prepared by conventional emulsification crosslinking method. The drug encapsulation efficiency (%), particle size, polydispersity index and zeta potential of polysorbate 80 coated R-HCl loaded chitosan nanoparticles were found satisfactory. These coated nanoparticles were characterized by SEM, FTIR and DSC analyses. In vitro drug release from different uncoated and coated chitosan nanoparticles showed initial burst release of R-HCl followed by a sustained release over 10 h. The coated nanoparticles were found stable over 3 months storage. In vivo biodistribution studies in Wistar rats exhibited higher R-HCl concentrations in brain with less accumulations of R-HCl in liver, spleen and kidney for polysorbate 80 coated R-HCl loaded chitosan nanoparticles after 1 h of dose administration (i.v.) as compared to these of uncoated R-HCl loaded chitosan nanoparticles and pure R-HCl. These observations suggested that the surface coated R-HCl loaded chitosan nanoparticles could be a useful tool to improve brain accumulation of R-HCl.

Rotating Membrane Emulsification for Producing Single and Multiple Emulsions

Membrane emulsification is a technique utilising a novel concept of generating droplet ‘drop by drop’ to produce emulsions. The technique has several distinctive advantages over the conventional emulsification techniques.This paper concerns on the development of membrane emulsification (Rotating Membrane Reactor, RMR) which utilizes rotating tubular membrane to initiate droplet detachments. The RMR uses a rotating stainless steel tubular membrane with laser drilled pores (100 μm pore diameter) and a syringe pump to drive the dispersed phase through the membrane at a given flow rate. O/W formulations were prepared with low viscosity of paraffin wax, two types of emulsifiers, different membrane rotation rate and dispersed phase flow rate. The emulsion droplets exhibited a coefficient of variation of 9% and 81μm droplet size. In this research, the pore size/droplet size ratio could achieve 0.8. This value was below than other membrane emulsification processes. The effects of principal system operating parameters on both the average droplet diameter and droplet uniformity were discussed. In addition, a multiple (W/O/W) emulsion formulation was investigated as well.

Biophenols-loaded solid lipid particles (SLPs) development by membrane emulsification

The present study investigates the preparation of biophenols-loaded solid lipid particles (SLPs) using the membrane emulsification process. This study involves two main novelties: the first is the encapsulation of amphiphilic/hydrophilic bioactive compounds in the hydrophobic matrix and the second is the use of cold membrane emulsification for the production of SLPs. The main objectives of this work were: i) to investigate the process parameters influencing the encapsulation efficiency in SLPs, (ii) to compare the membrane emulsification technique with conventional emulsification methods and (iii) to identify the operative conditions that allow to produce highly concentrated SLPs with improved encapsulation efficiency and low energy consumption. The influence of lipid phase compositions (cocoa butter, cocoa butter/ethyl acetate (4:1)) and the temperature of operation on the SLPs size, encapsulation efficiency and energy consumption was investigated. The membrane emulsification process allowed producing uniform particles with mean size corresponding to 3.6 times the pore size of the membrane. The encapsulation efficiency of hydroxytyrosol, an amphiphilic compound with antioxidant properties of the olive biophenol family, was about 2 times higher than with the homogenizer when the process was carried out at 40°C. The high solidification rate obtained when the process was carried out at room temperature determined an increase of the encapsulation efficiency up to 90%. The energy consumption associated with membrane emulsification process was two order of magnitude lower than the homogenizer.

Tracking the effect of microspheres size on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot in vitro and in vivo

The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95 ± 18.88 µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (Cmax = 110.1 ±54.2 ng/ml) and subsequent slow drug release (Cs(4–54d)= 2.7 ± 0.8 ng/ml) in vivo. Small microspheres (5.91 ± 2.24 µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (Cmax = 40.9 ± 13.7 ng/ml), whereas the drug release rate from 4 to 54 d was increased (Cs(4–54d)=4.1 ± 1.0 ng/ml). By further decreasing the size of microspheres to 3.38 ± 0.70 µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.

Nozzleless Fabrication of Oil-Core Biopolymeric Microcapsules by the Interfacial Gelation of Pickering Emulsion Templates.

Ionotropic gelation has been an attractive method for the fabrication of biopolymeric oil-core microcapsules due to its safe and mild processing conditions. However, the mandatory use of a nozzle system to form the microcapsules restricts the process scalability and the production of small microcapsules (<100 μm). We report, for the first time, a nozzleless and surfactant-free approach to fabricate oil-core biopolymeric microcapsules through ionotropic gelation at the interface of an O/W Pickering emulsion. This approach involves the self-assembly of calcium carbonate (CaCO3) nanoparticles at the interface of O/W emulsion droplets followed by the addition of a polyanionic biopolymer into the aqueous phase. Subsequently, CaCO3 nanoparticles are dissolved by pH reduction, thus liberating Ca(2+) ions to cross-link the surrounding polyanionic biopolymer to form a shell that encapsulates the oil droplet. We demonstrate the versatility of this method by fabricating microcapsules from different types of polyanionic biopolymers (i.e., alginate, pectin, and gellan gum) and water-immiscible liquid cores (i.e., palm olein, cyclohexane, dichloromethane, and toluene). In addition, small microcapsules with a mean size smaller than 100 μm can be produced by selecting the appropriate conventional emulsification methods available to prepare the Pickering emulsion. The simplicity and versatility of this method allows biopolymeric microcapsules to be fabricated with ease by ionotropic gelation for numerous applications.

Topical Semisolid Formulations of Hirsutenone and Accelerated Stability Assessment

To develop a topical preparation of hirsutenone (HST), a natural immunomodulator, we formulated oleaginous ointments and creams and assessed their stability in terms of shelf‐life. Ointments were prepared by mixing the molten lipid phase of white petrolatum and white beeswax with glycerin and propylene glycol, in which HST was dissolved with ascorbyl palmitate (AP), butylated hydroxyl toluene (BHT), or ethylenediaminetetraacetic acid (EDTA) as an antioxidant. Reference oil‐in‐water creams were formulated by conventional emulsification. The ointment and cream formulations were subjected to accelerated stability testing at 40 °C. At appropriate time points, test samples were dissolved in organic solvent, diluted with methanol, and filtered prior to high‐performance liquid chromatography (HPLC). The degradation of HST in cream and ointment formulations followed first‐order kinetics. The rate constants (day−1) of HST in cream and ointments were 1.71 × 10−2 and 0.67 × 10−2, respectively, revealing a 2.5‐fold greater half‐life in ointments than in creams. Although AP and BHT had no effect on chemical stabilization of ointments, EDTA enhanced the stability of HST at 40 °C. The shelf‐lives of HST formulations were estimated by the Q10 method. Assuming a Q10 value of 2, the shelf‐lives (days) of cream, ointment, and ointment with EDTA at 25 °C were 14.99, 38.23, and 44.19, respectively. At 4 °C, the shelf‐life of HST in ointment with EDTA was extended to 220 days. Even though the stability of HST was somewhat increased by the ointment formulation and further improved by adding EDTA, alternative approaches are needed to increase stabilization.

Silicone oil emulsions: strategies to improve their stability and applications in hair care products

Silicone oils have wide range of applications in personal care products due to their unique properties of high lubricity, non-toxicity, excessive spreading and film formation. They are usually employed in the form of emulsions due to their inert nature. Until now, different conventional emulsification techniques have been developed and applied to prepare silicone oil emulsions. The size and uniformity of emulsions showed important influence on stability of droplets, which further affect the application performance. Therefore, various strategies were developed to improve the stability as well as application performance of silicone oil emulsions. In this review, we highlight different factors influencing the stability of silicone oil emulsions and explain various strategies to overcome the stability problems. In addition, the silicone deposition on the surface of hair substrates and different approaches to increase their deposition are also discussed in detail.

Emulsification liquid phase microextraction followed by on-line phase separation coupled to high performance liquid chromatography

An emulsification liquid phase microextraction followed by on-line phase separation coupled to high performance liquid chromatography (HPLC) is introduced based on a novel idea for the separation of dispersed organic phase from aqueous phase. In this method, the dispersed organic extraction phase was filtered using an in-line filter and it was separated from the water sample. The new approach is simple and, in addition to improving some limitations of the conventional emulsification liquid phase microextraction, eliminates the need for centrifugation in the phase separation step.To demonstrate the applicability of the method, it was applied for the extraction and determination of trace amounts of selected parabens as model analytes. In this procedure, 30μL of 1-octanol was injected slowly into 10mL of the aqueous sample inside the ultrasonic water bath. Then, the emulsion formed was passed through the in-line filter located in the loop of the HPLC valve and the organic extraction phase was separated and it was retained in the filter. By changing the position of the valve, the filter was located in the mobile phase pass and the retained organic phase was eluted and transferred to the separation column. The effects of some important parameters such as types of extraction solvent and its volume, ionic strength, and ultrasonication time on extraction efficiency were investigated and optimized. Under optimal conditions, preconcentration factors and limits of detection for the compounds studied were obtained in the ranges of 289–595 and 0.05–0.2μgL−1, respectively. Finally, the method was successfully applied to determine selected parabens in some water and cosmetic samples.