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Preparation of a W/O/W double emulsion in two steps: a high-shear emulsification step with lipophilic surfactants for the W/O emulsion (a) and a low shear emulsification step with hydrophilic surfactants for the W/O/W emulsion (b).
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Double emulsions have potential for the production of low calorie food products, encapsulation of medicines and other high value products. The main issue is the difficulty to efficiently produce double emulsions in a well controlled manner due to their shear sensitivity. In membrane emulsification only mild shear stresses are applied and it is ther...
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... mm. Emulsions of this kind are thermodynamically unstable, which means that there is a tendency to reduce the interface (as a result of a relatively high interfacial tension), causing the droplets to coalesce and therewith decreasing the total amount of interface. Usually double emulsions are prepared in a two-step emul- sification process (see Fig. 1) using two surfactants; a hy- drophobic one designed to stabilize the interface of the W/O internal emulsion and a hydrophilic one for the external in- terface of the oil globules (for W/O/W emulsions). The pri- mary W/O emulsion is prepared under high-shear conditions to obtain small droplets while the secondary emulsification step is ...
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... These emulsions can be categorized under multiple or complex emulsions. The key advantages of using microfluidic technologies in producing complex emulsions over other methods such as membrane emulsification (detailed review on membrane emulsification-based production of complex emulsions can be found here [26][27][28]) are presented hereafter. Microfluidic technologies have ushered in an era of unprecedented precision and control in the realm of droplet generation over traditional homogenization techniques [8]. ...
... Pharmaceutics 2024, 16, x FOR PEER REVIEW 4 of 28 of using microfluidic technologies in producing complex emulsions over other methods such as membrane emulsification (detailed review on membrane emulsification-based production of complex emulsions can be found here [26][27][28]) are presented hereafter. ...
This review explores the intersection of microfluidic technology and complex emulsion development as a promising solution to the challenges of formulations in multi-drug therapy (MDT) and polypharmacy. The convergence of microfluidic technology and complex emulsion fabrication could herald a transformative era in multi-drug delivery systems, directly confronting the prevalent challenges of polypharmacy. Microfluidics, with its unparalleled precision in droplet formation, empowers the encapsulation of multiple drugs within singular emulsion particles. The ability to engineer emulsions with tailored properties—such as size, composition, and release kinetics—enables the creation of highly efficient drug delivery vehicles. Thus, this innovative approach not only simplifies medication regimens by significantly reducing the number of necessary doses but also minimizes the pill burden and associated treatment termination—issues associated with polypharmacy. It is important to bring forth the opportunities and challenges of this synergy between microfluidic-driven complex emulsions and multi-drug therapy poses. Together, they not only offer a sophisticated method for addressing the intricacies of delivering multiple drugs but also align with broader healthcare objectives of enhancing treatment outcomes, patient safety, and quality of life, underscoring the importance of dosage form innovations in tackling the multifaceted challenges of modern pharmacotherapy.
... Review in another aqueous solution containing a hydrophilic emulsifier, resulting in the formation of a double water-in-oilin-water (w/o/w) emulsion using either sonication or membrane emulsification. 148 Typically, two surfactants are used in this process: one hydrophobic surfactant to stabilize the interface of the water-in-oil (w/o) internal emulsion and one hydrophilic surfactant for the external interface of the oil globules. Microemulsion methods can produce LNPs loaded with various drug compounds, such as Baclofen, Idarubicin, Ketoprofen, Nevirapine, and Tobramycin. ...
Over the past decade, the therapeutic potential of nanomaterials as novel drug delivery systems complementing conventional pharmacology has been widely acknowledged. Among these nanomaterials, lipid-based nanoparticles (LNPs) have shown remarkable pharmacological performance and promising therapeutic outcomes, thus gaining substantial interest in preclinical and clinical research. In this review, we introduce the main types of LNPs used in drug formulations such as liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, and lipid polymer hybrid nanoparticles, focusing on their main physicochemical properties and therapeutic potential. We discuss computational studies and modeling techniques to enhance the understanding of how LNPs interact with therapeutic cargo and to predict the potential effectiveness of such interactions in therapeutic applications. We also analyze the benefits and drawbacks of various LNP production techniques such as nanoprecipitation, emulsification, evaporation, thin film hydration, microfluidic-based methods, and an impingement jet mixer. Additionally, we discuss the major challenges associated with industrial development, including stability and sterilization, storage, regulatory compliance, reproducibility, and quality control. Overcoming these challenges and facilitating regulatory compliance represent the key steps toward LNP’s successful commercialization and translation into clinical settings.
... Janus particles can have two different colors, electrical properties, magnetic properties, hydrophilicity, selective solubilities, etc., to achieve different functions, including drug release, liquid crystal display, and self-assembly. 18 The traditional preparation method for compound droplets [19][20][21] is to destroy the interface of two immiscible fluids using an external force field to form droplets, and secondary emulsification of the droplets can then generate compound droplets. However, the traditional method leads to poor monodispersity of the generated droplets due to the uneven application of an external force. ...
A numerical investigation of the deformation of compound microdroplets transported inside a circular microchannel is described in this article. Two droplet morphologies are considered (shell-core and Janus), which correspond to nonequilibrium and equilibrium states, respectively, based on the balancing of the three interfacial tensions at the triple line. Numerical simulations coupled with a three-phase volume-of-fluid method are performed on axisymmetric models to consider both the absence and presence of a triple line. In addition to adaptive mesh refinement on the interfaces, topology-oriented refinement is used to resolve thin films between the shell and core droplets. After experimental validation, the effects of flow rates, physical properties, and confinement conditions are considered. In the reference frame of the droplets, there are five inner vortexes inside the shell-core droplet, while only three are present inside the Janus droplet, the same as single-phase droplets. For shell-core droplets, the aspect ratio of the shell droplet decreases with the capillary number of the continuous phase and droplet sizes, while sudden jumps are identified when the thin film forms between the shell and core interfaces. Conversely, the aspect ratio of the core droplet increases and then decreases when the shape of the core droplets is influenced by the flow and space confinements. With Janus droplets, the aspect ratio decreases with the capillary number. The axial length of the front portion decreases with the capillary number and then reaches a plateau with small variations, while that of the rear portion increases nearly linearly.
... ELM based various extraction systems are essentially double emulsions that exist as W/O/W (water-in-oil-in-water) and O/W/O (oil-in-water-in-oil), where metal ions from wastewater were usually recovered by utilizing the W/O/W type emulsions, here the organic phase separates the encapsulated internal phase droplets in the emulsion from the aqueous feed [102][103][104][105][106][107][108]. Two steps are usually involved in the formation of ELM, which are the formation of primary emulsion and the formation of emulsion liquid membrane. ...
... The emulsifier not only lowers the surface tension (γ) in order to facilitate the break-up of emulsion droplets but also to prevent the formed emulsion droplets from recoalescing [102,103]. ...
Over the past few decades, ELM based separation processes have become an attractive and efficient way to remove toxic metal ions from the various aqueous waste effluent streams. This paper provides a comprehensive review of the generation, characterization, and applications of emulsion liquid membrane (ELM) from the more than 280 papers and books published so far. First, the ELM formation and the transport mechanism are introduced. Then the ELM stability and emulsion splitting methods are discussed in detail, followed by the latest research and findings of the extraction of copper and nickel using the ELM technique during the past few decades, including a thorough discussion of ELM operating parameters that impact ELM stability and extraction. In addition, the kinetics study and industrial application of this technique for the removal of coppers/nickel solutes are also presented and discussed.
... Double emulsions are mainly used in food, cosmetics, and pharmaceutical industries [3]. Due to their characteristic structure, double emulsions are used to encapsulate value-giving ingredients, such as active ingredients in the pharmaceutical industry [4] or vitamins in foods [5]. ...
Double emulsions arouse great interest in various industries due to their ability to encapsulate value-adding ingredients. However, they tend to be unstable due to their complex structure. Several measurement techniques have already been developed to study and monitor the stability of double emulsions. Especially for the measurement of the filling degree of double emulsions, so far there is no reliable method available. In this paper, a measurement system is presented that can measure the filling degree of water-in-oil-in-water (W/O/W) double emulsions by both spectrometrical and photometrical means. The method is based on the Raman effect and does not require any sample preparation, and the measurement has no negative influence on the double emulsion. It is shown that both spectrometric and photometric Raman techniques can reliably distinguish between double emulsions with filling degrees that have a 0.5% difference. Additionally, oil droplet sizes can be photometrically measured. Furthermore, the measurement system can be integrated into both inline and online emulsification processes.
... The continuous phase can subsequently undergo evaporation to produce nanoparticles [469,470]. Nano-emulsion can be simple composing of dispersed phase and continuous phase; oil in water (O/W) emulsion or water in oil (W/O) emulsion, or multiple emulsion; water-in-oil-in-water (W/O/W) or oil-in-water-in-oil (O/W/O) [471,472]. The hydrophobic drugs is loaded in the oily phase where the used oils are propositioned on solubility of drug for emulsification purpose, whereas hydrophilic drugs are loaded in the aqueous phase ( Fig. 3) [473]. ...
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In this review, a comprehensive analysis of flavonoid-based nanomedicine was provided with special emphasis on tumor microenvironment components as therapeutic targets. Studies discussed in this review provide a solid ground for researchers and physicians to consider flavonoid based nano- formulations as possible adjuvant therapies with conventional anticancer agents.
... Most of the samples prepared by MA showed larger droplet sizes than those obtained by DME ( Figure S1, supplementary material), since, in conventional emulsification processes, high-shear stresses are needed to decrease the droplet size and must be considered according to the viscosity of the oil phase [22]. It is important to note that DME normally led to droplet sizes of around 2-10 times the membrane pore diameter used [25,32]. ...
... However, in the case of DEs, it is observed when W 1 water drops migrate from the oil phase to the external W 2 [44,45]. As a general trend, the DEs prepared by DME showed lower size variations, resulting, therefore, in more stable and more controlled droplet size, in agreement with previous studies [22,27]. ...
Pomegranate peel is an agro-industrial waste that can be used as source of punicalagin, a polyphenolic compound with several beneficial effects on health. Since, once extracted, punicalagin is prone to degradation, its encapsulation by double emulsions can be an alternative to protect the active compound and control its release. The aim of this investigation was to evaluate the feasibility of encapsulating pomegranate peel extract (PPE) in double emulsions using different types of oils (castor, soybean, sunflower, Miglyol and orange) in a ratio of 70:30 (oil:PPE) and emulsification methods (direct membrane emulsification and mechanical agitation), using polyglycerol polyricinoleate (PGPR) and Tween 80 as lipophilic and hydrophilic emulsifiers, respectively. Direct membrane emulsification (DME) led to more stable emulsions during storage. Droplet size, span values, morphology and encapsulation efficiency (EE) were better for double emulsions (DEs) prepared by DME than for mechanical agitation (MA). DEs formulated using Miglyol or sunflower oil as the oily phase could be considered as suitable food grade systems to encapsulate punicalagin with concentrations up to 11,000 mg/L of PPE.
... Apple (peel) • Cyanidin-3-glucoside • Cyanidin-3-arabinoside 5-130 (Wu et al. 2006) Blood orange • Cyanidin-3-(6″-malonyl)-beta-glucoside • Malvidin-3-glucoside 60-160 (Tokuşoğlu and Hall 2011;Fallico et al. 2017 ...
Anthocyanins (ACNs) are notable hydrophilic compounds that belong to the flavonoid family, which are available in plants. They have excellent antioxidants, anti-obesity, anti-diabetic, anti-inflammatory, anticancer activity, and so on. Furthermore, ACNs can be used as a natural dye in the food industry (food colorant). On the other hand, the stability of ACNs can be affected by processing and storage conditions, for example, pH, temperature, light, oxygen, enzymes, and so on. These factors further reduce the bioavailability (BA) and biological efficacy of ACNs, as well as limit ACNs application in both food and pharmaceutics field. The stability and BA of ACNs can be improved via loading them in encapsulation systems including nanoemulsions, liposomes, niosomes, biopolymer-based nanoparticles, nanogel, complex coacervates, and tocosomes. Among all systems, biopolymer-based nanoparticles, nanohydrogels, and complex coacervates are comparatively suitable for improving the stability and BA of ACNs. These three systems have excellent functional properties such as high encapsulation efficiency and well-stable against unfavorable conditions. Furthermore, these carrier systems can be used for coating of other encapsulation systems (such as liposome). Additionally, tocosomes are a new system that can be used for encapsulating ACNs. ACNs-loaded encapsulation systems can improve the stability and BA of ACNs. However, further studies regarding stability, BA, and in vivo work of ACNs-loaded micro/nano-encapsulation systems could shed a light to evaluate the therapeutic efficacy including physicochemical stability, target mechanisms, cellular internalization, and release kinetics.
... A distinctive feature of microfluidics is that the combination of single-stage channels can be upgraded to a complex microchannel network system, providing conditions for the controlled construction of double and multiple emulsion droplets [24]. Single emulsion droplets are usually produced by two immiscible liquid phases, with one phase dispersed into the second [25], the double emulsion can be viewed as the dispersion of a primary emulsion in another aqueous or oil phase [26][27][28], and multiple emulsion can be formed by multiple-step emulsification of multiphase fluids in microchannels [29]. In order to prepare multi-layered microparticles, a microfluidic device with several nested microchannels is usually required. ...
In this work, we used a co-flow microfluidic device with an injection and a collection tube to generate droplets with different layers due to phase separation. The phase separation system consisted of poly(ethylene glycol) diacrylate 700 (PEGDA 700), PEGDA 250, and sodium alginate aqueous solution. When the mixture droplets formed in the outer phase, PEGDA 700 in the droplets would transfer into the outer aqueous solution, while PEGDA 250 still stayed in the initial droplet, breaking the miscibility equilibrium of the mixture and triggering the phase separation. As the phase separation proceeded, new cores emerged in the droplets, gradually forming the second and third layers. Emulsion droplets with different layers were polymerized under ultraviolet (UV) irradiation at different stages of phase separation to obtain microspheres. Microspheres with different layers showed various release behaviors in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release rate decreased with the increase in the number of layers, which showed a potential application in sustained drug release.
... One of the critical elements that determines the efficacy of this technique is the intrinsic stability of the internal W/O emulsion. It is worth mentioning that the presence of hydrodynamic perturbations during the second stage of emulsification must not lead to any significant breakdown of the primary W/O emulsion in order to obtain stable W/O/W emulsions [6]. ...
In this study, the effects of sodium caseinate (NaCN; emulsifier) concentration, a type of hydrophilic emulsifier, as well as concentration of primary W/O emulsion on the stability of water–oil-water (W/O/W) emulsions were investigated. Emulsions were made using two different emulsification techniques including ultrasonic liquid processing and high pressure homogenization (HPH). Microscopy images of W/O/W emulsions in combination with droplet size analysis and viscosity measurements showed that the sample with a higher percentage of primary W/O emulsion (50 wt% vs. 40 wt% and 25 wt%) was more resistant to coalescence (narrower droplet size distribution and lower creaming index). The higher stability of this emulsion at 50 wt% is due to the enhancement in the solution viscosity which slows down the coalescence and destabilization kinetics. The increase in the NaCN concentration from 0.3 wt% to 0.9 wt% (based on total weight of emulsion) led to formation of larger droplets possibly due to the destabilization of primary W/O emulsion through the disruption of polyglycerol polyricinoleate (PGPR) layer. Regarding the effect of emulsifier type, incorporation of Cremophor EL and Tween 60 in comparison with NaCN resulted in formation of smaller droplet size due to their enhanced surface activity at the interface. Finally, we found that using high pressure homogenizer (HPH) instead of ultrasonic processor was detrimental to the emulsion stability and size distribution. These findings further provide new pathways to design emulsion systems for food and drug delivery applications.
