Preparation characteristics of water-in-oil-in-water multiple emulsions using microchannel emulsification

Microchannel (MC) emulsification is a novel technique for preparing monodispersed emulsions. This study demonstrates preparing water-in-oil-in-water (W/O/W) emulsions using MC emulsification. The W/O/W emulsions were prepared by a two-step emulsification process employing MC emulsification as the second step. We investigated the behavior of internal water droplets penetrating the MCs. Using decane, ethyl oleate, and medium-chain triglyceride (MCT) as oil phases, we observed successful MC emulsification and prepared monodispersed oil droplets that contained small water droplets. MC emulsification was possible using triolein as the oil phase, but polydispersed oil droplets were formed from some of the channels. No leakage of the internal water phase was observed during the MC emulsification process. The internal water droplets penetrated the MC without disruption, even though the internal water droplets were larger than the resulting W/O/W emulsion droplets. The W/O/W emulsion entrapment yield was measured fluorometrically and found to be 91%. The mild action of droplet formation based on spontaneous transformation led to a high entrapment yield during MC emulsification.     

Preparation of Uniform Microspheres and Microcapsules by Modified Emulsification Process

Summary: Uniform microspheres and microcapsules have been prepared by developing a direct membrane emulsification technique from O/W, W/O and W/O/W emulsions in previous studies, and have been applied in bio-separation and drug delivery systems. The diameter can be controlled from several microns to above 100 microns. However, smaller microsphere with submicron size, especially from W/O/W emulsion was difficult to be prepared. In this article, a modified emulsification technique was developed to overcome the problem. That is, a pre-emulsion (W/O or W/O/W) with broad size distribution of droplets was prepared firstly by homogenization, sonification or mechanical stirring method, then the pre-emulsion was pressed through the uniform pores of a Shirasu Porous Glass (SPG) membrane to obtain relatively uniform smaller droplets, finally the droplets were solidified to form uniform microsphere or microcapsule. Uniform chitosan microsphere and poly(lactic-glycolic acid) (PLGA) microcapsule with submicron size were prepared from W/O and W/O/W emulsions, respectively. Further more, uniform polymer-magnetite microcapsule was prepared by combining this technique and a new post-precipitation process of magnetite.     

Preparation of microcapsule-supported palladium catalyst using SPG (Shirasu Porous Glass) emulsification technique

<正>A new method for the preparation of microcapsule-supported palladium catalyst was described.The highly monodisperse crosslinked polystyrene microcapsules containing phosphine ligand were synthesized by the self-assembling of phase separated polymer (SaPSeP) method using diphenyl(4-vinylphenyl) phosphine and divinylbenzene as a monomer and crosslinking agent,respectively, and 2,2'-azobisisobutyronitrile(AIBN) as an initiator within the droplets of oil-in-water(O/W) emulsions,which were prepared by using the Shirasu Porous Glass(SPG) membrane emulsification technique.The prepared microcapsule-supported palladium catalyst exhibited high catalytic activity for Heck reaction and can be reused several times without loss of activity.     

Study of SPG membrane emulsification processes for the preparation of monodisperse core-shell microcapsules

Experimental investigations on the Shirasu-porous-glass (SPG)-membrane emulsification processes for preparing monodisperse core-shell microcapsules with porous membranes were carried out systematically. The results showed that, to get monodisperse oil-in-water (O/W) emulsions by SPG membrane emulsification, it was more important to choose an anionic surfactant than to consider hydrophile-lipophile balance (HLB) matching. Increasing the viscosity of either the disperse phase or the continuous phase or decreasing the solubility of the disperse phase in the continuous phase could improve both the monodispersity and the stability of emulsions. With increasing monomer concentration inside the disperse phase, the monodispersity of emulsions became slightly worse and the mean diameter of emulsions gradually became smaller. Monodisperse monomer-containing emulsions were obtained when the SPG membrane pore size was larger than 1.0 micro m, and from these emulsions satisfactory monodisperse core-shell microcapsules with a porous membrane were prepared. On the other hand, when the SPG membrane pore size was smaller than 1.0 mciro m, no monodisperse emulsions were obtained because of the formation and chokage of solid monomer crystals in the pores or at the end of the pores of the SPG membrane. This was due to the remarkable solvation and diffusion of the solvent in water. With increasing the emulsification time the average emulsion diameter generally decreased, and the monodispersity of the emulsions gradually became worse.     

Controlling the stability and size of double-emulsion-templated poly(lactic-co-glycolic) acid microcapsules

The stability and size of poly(lactic-co-glycolic)acid (PLGA)-containing double emulsions and the resulting PLGA microcapsules are controlled by varying the composition of highly monodisperse water-in-oil-in-water (W/O/W) double emulsions. We propose that the basic inner phase of W/O/W double emulsions catalyzes the hydrolysis of PLGA and the ionization of carboxylic acid end groups, which enhances the surface activity of PLGA and facilitates the stabilization of the double emulsions. The size of PLGA-containing double emulsions and that of resulting microcapsules can be readily tuned by osmotic annealing, which depends on the concentration ratio of a solute in the inner and outer phases of double emulsions. The internal volume of PLGA microcapsules can be changed by more than 3 orders of magnitude using this method. This approach also overcomes the difficulty in generating monodisperse double emulsions and microcapsules over a wide range of dimensions using a single microfluidic device. The osmotic annealing method can also be used to concentrate encapsulated species such as colloidal suspensions and biomacromolecules.     

Preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) hollow microcapsules

We successfully developed a novel and simple method for preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) hollow microcapsules at the interface of water-in-oil (W/O) single emulsions at a temperature below the lower critical solution temperature (LCST) of PNIPAM. The prepared PNIPAM microcapsules are featured with hollow structures and thin membranes, high monodispersity, excellent reversible thermo-sensitivity and fast response to environmental temperature. This approach exhibits great interests in preparing monodisperse thermo-sensitive microcapsules for encapsulating bioactive materials or drugs requiring mild encapsulation conditions, because of the flexibility in choosing substances being dissolved in the aqueous phase. The preparation methodology demonstrated in this study provides a unique approach for preparing monodisperse hollow polymeric microcapsules with W/O single emulsions.     

A review of: “Nineteenth Century Attitudes: Men of Science (Chemists and Chemistry Series,Vol. 13)”. Sydney Ross. Kluwer Academic Publishers; Dordrecht, 1991. pp. xi+235. $69.00.

Abstract

The potential of polytetrafluoroethylene (PTFE) membranes as water‐in‐oil (W/O) emulsification devices was investigated to obtain uniformly sized droplets and to convert them into microcapsules and polymer particles via subsequent treatments. Uniform W/O emulsion droplets have not been achieved using glass membranes unless the membrane was rendered hydrophobic by treatment with silanes. If a PTFE membrane is capable of providing uniform droplets for a W/O emulsion, a coordinated membrane emulsification system can be established since glass membranes have been so successful for O/W (oil‐in‐water) emulsification. In order to examine the feasibility of PTFE membrane emulsification, O/W and W/O emulsion characteristics prepared using PTFE membranes were compared with those prepared by the conventional SPG (Shirasu porous glass) membrane emulsification method. A 3 wt.% sodium chloride solution was dispersed in kerosene using a low HLB surfactant. Effects of the membrane pore size, permeation pressure, and the type of emulsifiers and concentration on the droplet size and on the size distribution (CV, coefficient of variation) were investigated. The CV of the droplets was fairly low, and the average droplet size was correlated with the critical permeation pressure of the dispersed phase, revealing that the PTFE membrane could be used as a one‐pass membrane emulsification device. Low CV values were maintained with a Span 85 (HLB = 1.8) concentration, 0.2–5.0 wt.% and a range of HLB from 1.8–5.0. For a brief demonstration of practical applications, nylon‐6,10 microcapsules prepared by interfacial polycondensation and poly(acrylamide) hydrogels from inverse suspension polymerization are illustrated.     

Novel asymmetric through-hole array microfabricated on a silicon plate for formulating monodisperse emulsions

We have proposed a novel microchannel (MC) structure for formulating monodisperse emulsions. The emulsification device is a silicon array of microfabricated, asymmetric through-holes with a slit and a circular channel (an asymmetric straight-through MC). The asymmetric through-holes of a uniform size stably yielded monodisperse emulsions with average droplet diameters of 35-41 mum and coefficients of variation of less than 2% by forcing the to-be-dispersed phase into the continuous phase via the through-holes. Their asymmetry enabled the stable formation of monodisperse emulsion droplets by spontaneous transformation, even using a to-be-dispersed phase with a very low viscosity below 1 mPa s. Additionally, the asymmetric straight-through MC with a high-density through-hole layout has the potential for high-throughput formulation of monodisperse emulsions.     

Preparation of monodisperse crosslinked polymelamine microcapsules by phase separation method

Monodisperse polymelamine microcapsules were prepared by phase separation method. Control of microcapsule diameter was investigated using the uniform-sized oil-in-water emulsion droplets as the capsule core. The monodisperse emulsion droplets were prepared using the Shirasu porous glass (SPG) membrane emulsification technique. The effects of the diameter of the oil droplet and concentration of sodium dodecyl sulfate (SDS), which is a typical emulsifier in SPG membrane emulsification, on microencapsulation were investigated. The microcapsules were aggregated when oil droplets with small size were microencapsulated at high SDS concentration. To reduce the SDS concentration, the creamed emulsion was used. The monodisperse polymelamine microcapsules were successfully prepared by using the creamed emulsion. The microcapsule diameter was almost similar to the diameter of the encapsulated oil droplet. The coefficient of variation values was about 10% for all microcapsules prepared in this study. Control of microcapsule diameter was achieved in the range of 5–60 μm.     

Effect of interfacial tension on the dynamic behavior of droplet formation during microchannel emulsification

Microchannel (MC) emulsification is a novel technique for producing monodisperse emulsions. In this study, we investigated the effect of interfacial tension on the dynamic behavior of droplet formation with various surfactant concentrations. Interfacial tension did not affect the resultant droplet diameter in lower flow velocity ranges, but it did affect the time-scale parameters. These results were interpreted using the droplet formation mechanism reported in our previous study. At surfactant concentrations below 0.3%, the emulsification behavior was differed from that at higher surfactant concentrations. An analysis of diffusional transfer indicated that dynamic interfacial tension affects the emulsification behavior at lower surfactant concentrations. Dynamic interfacial tension that exceeded the equilibrium value led to a shorter detachment time. This resulted in stable droplet formation of monodispersed emulsions by spontaneous transformation, even at flow velocities above the predicted critical flow velocity. A previous study predicted that the droplet formation would become unstable and polydispersed larger droplets would form over critical flow velocity. Wetting of the MC with the dispersed phase at lower surfactant concentrations induced formation of larger polydispersed droplets at high flow velocities.     

Water mass transfer in W/O emulsions

Water transportation through the oil phase in W/O emulsions and in W1/O/W2 systems (W/O emulsion in contact with water) was examined. Substance diffusion through interfaces led to interface instability and spontaneous emulsification which caused nanodispersion formation. The photomicrographs of Pt/C replicas of emulsions showed the presence in the continuous oil phase a lot of nanodispersion droplets with a diameter in the range 17-25 nm. Diffusion coefficient (D) of water calculated on the base of Lifshiz-Slezov-Wagner (LSW) equation was about 15 times lower than the coefficients of molecular diffusion. Since such emulsions were extremely unstable toward coalescence, the growth of water droplets took place through as Ostwald ripening as coalescence. In three-phase W1/O/W2 systems diffusion of water, Rhodamine C, and ethanol was studied. D calculated on the base of the equation of nonstationary diffusion were approximately 1000 times lower than molecular ones. It was assumed, that nanodispersion droplets were more likely water carriers in investigated W/O emulsions stabilized by sorbitan monooleate.     

Differential scanning calorimetry (DSC) in multiple W/O/W emulsions

Multiple water-in-oil-in-water (W/O/W) emulsions offer a huge potential as encapsulation systems in different food, cosmetic, and pharmaceutical applications. Because of their complex structure, however, it is difficult to characterize these systems. Typical measurement techniques to determine the size and stability of the inner water droplets encapsulated in the oil droplets show limitations and inaccuracies. Determining the total amount of water in the inner droplets is most often done by indirect methods to date. We describe an analytical method based on differential scanning calorimetry (DSC) for characterizing the total amount of encapsulated water droplets and their stability in W/O/W multiple emulsions. It uses the possibility to directly determine the latent heat of freezing of water droplets of the same size and composition as in the multiple emulsions. The amount of water in the inner droplets of a W/O/W emulsion can thus be calculated very accurately. It is shown that this method enables furthermore detecting multi-modalities in the size distribution of inner water droplets in W/O/W emulsions. Changes in droplet size distribution of the inner droplets occurring during the second emulsification step of processing or during storage can be detected. DSC thus offers a powerful tool to characterize the structure of multiple W/O/W emulsions.     

Stabilization of Water‐Soluble Antioxidant in Water‐in‐Oil‐in‐Water Double Emulsions

Abstract

In this study, we are introducing a method that can effectively stabilize antioxidants in water‐in‐oil‐in‐water (W/O/W) double emulsions. Preliminarily, stable W/O/W double emulsions were produced by manipulating the characteristics of internal aqueous phase via two‐stage emulsification, resulting consequently in the formation of fine internal water droplets in the dispersed oil droplets. From conductivity measurements that can determine the elution amount of internal aqueous phase, it was confirmed that the double emulsion stability could be improved by treating the internal aqueous phase with a hydroxypropyl‐beta‐cyclodextrin. In this study, kojic acid, 5‐hydroxy‐2‐(hydroxymethyl)‐4‐pyrone was selected as a model antioxidant. The stabilization of kojic acid was attempted by locating it in the internal water droplets of the stable W/O/W double emulsions. The stability of kojic acid in the double emulsion system could be maintained at 90% for 10 weeks at high temperature. We believe that these stable W/O/W double emulsions could be used meaningfully as a carrier for many unstable antioxidants.     

Emulsifying potency of new amino acid-type surfactant (II): stable water-in-oil (W/O) emulsions containing 85 wt% inner water phase

The ternary phase diagram for N-[3-lauryloxy-2-hydroxypropyl]-L-arginine L-glutamate (C12HEA-Glu), a new amino acid-type surfactant, /oleic acid (OA)/water system was established. The liquid crystal and gel complex formations between C12HEA-Glu and OA were applied to a preparation of water-in-oil (W/O) emulsions. Stable W/O emulsions containing liquid paraffin (LP) as the oil and a mixture of C12HEA-Glu and OA as the emulsifier were formed. The preparation of stable W/O emulsions containing 85 wt% water phase was also possible, in which water droplets would be polygonally transformed and closely packed, since the maximum percentage of inner phase is 74% assuming uniformly spherical droplets. Water droplets would be taken into the liquid crystalline phase (or the gel complex) and the immovable water droplets would stabilize the W/O emulsion system. The viscosity of emulsions abruptly increased above the 75 wt% water phase (dispersed phase). The stability of W/O emulsions with a lower weight ratio of OA to C12HEA-Glu and a higher ratio of water phase was greater. This unusual phenomenon may be related to the formation of a liquid crystalline phase between C12HEA-Glu and OA, and the stability of the liquid crystal at a lower ratio of oil (continuous phase). W/O and oil-in-water (O/W) emulsions containing LP were selectively prepared using a mixture of C12HEA-Glu and OA since the desirable hydrophile-lipophile balance (HLB) number for the emulsification was obtainable by mixing the two emulsifiers.     

Phase transitions and microstructure of emulsion systems prepared with acylglycerols/zinc stearate emulsifier

The emulsification processes, during which acylglycerols/zinc stearate emulsifier, water, and oil phase formed ternary systems, such as water-in-oil (W/O) emulsions, oil-in-water (O/W) dispersions, and unstable oil-water mixtures, were investigated in order to characterize the progressive transformations of the dispersed systems. The type, structure, and phase transitions of the systems were found to be determined by temperature and water phase content. Crystallization of the emulsifier caused the destabilization and subsequent phase inversion of the emulsions studied, at a temperature of 60-61 degrees C. The observed destabilization was temporary and led, at lower temperature, to W/O emulsions, "O/W + O" systems, or O/W dispersions, depending on the water content. Simultaneous emulsification and cooling of 20-50 wt % water systems resulted in the formation of stable W/O emulsions that contained a number of large water droplets with dispersed oil globules inside them ("W/O + O/W/O"). In water-rich systems (60-80 wt % of water), crystallization of the emulsifier was found to influence the formation of crystalline vesicle structures that coexisted, in the external water phase, with globules of crystallized oil phase. Results of calorimetric, rheological, and light scattering experiments, for the O/W dispersions obtained, indicate the possible transition of a monostearoylglycerol-based alpha-crystalline gel phase to a coagel state, in these multicomponent systems.     

Controlled generation of monodisperse discoid droplets using microchannel arrays

We report a novel technique for generating geometrically confined droplets using a unique microstructure composed of a microchannel (MC) array and a shallow well. Silicon MC array devices were successfully used to generate monodisperse discoid droplets of oil-in-water (O/W) and W/O types by forcing a to-be-dispersed phase through channels into a well filled with a continuous phase. Monodisperse discoid droplets with sizes down to several micrometers were obtained by controlling the channel and well dimensions. The resultant discoid droplets formed a mostly close-packed array in the well. Monodisperse discoid droplets consisting of a silicone oil/water/sodium dodecyl sulfate system did not coalesce during the storage time of seven days. Additionally, MC array plates with many channels can be useful for increasing the droplet productivity of a single microfluidic device.     

Preparation of uniformly sized alginate microspheres using the novel combined methods of microchannel emulsification and external gelation

The purpose of this study was to prepare alginate (ALG) microspheres with narrow size distribution using a combination of microchannel (MC) emulsification technique and external gelation method. ALG solution was dispersed as water-in-oil (W/O) emulsion droplets in iso-octane containing 5 wt% Span 85 as the immiscible continuous phase via MC emulsification technique using hydrophobic MC array. The MC array used in this experiment is a grooved-type MC consisting of 1070 channels fabricated on a 25 mm × 28 mm silicon microchip. The monodisperse W/O emulsion droplets generated from the MCs were in the mean particle diameter (d_av) range of 18–22 μm and coefficient of variation (CV) of 5–26% at the ALG concentrations of 0.5–3.0 wt% and flow rates of 0.05–0.4 mL/h. The d_av of the emulsion droplets hardly changed below a dispersed phase threshold flow rate of 0.2 mL/h but gradually became smaller when the dispersed phase concentration was increased. The resulting emulsion droplets were then congealed to form rigid ALG gel particles by reacting them with calcium chloride (CaCl₂) solution. Gelation of the ALG droplets by calcium ion (Ca²⁺) resulted in shrinkage of its d_av, forming uniformly sized ALG microspheres with an average diameter of 6.2 μm and a CV of below 10% at the ALG concentration of 3 wt%.     

Microcapsule synthesis via RAFT photopolymerization in vegetable Oil as a green solvent

Polymeric capsules with an aqueous core have great potential for a wide range of applications, for example food/biomedical applications. However, synthesis of such capsules often involves the use of toxic organic solvents. Herein, an organic solvent‐free approach is developed for the synthesis of polymeric microcapsules with an aqueous core. The method is based on RAFT polymerization of divinyl monomer around the periphery of inverse emulsion water droplets acting as templates, with an amphiphilic macroRAFT species fulfilling the dual roles of RAFT agent and colloidal stabilizer. Vegetable oils, which are non‐toxic and renewable, are used as the continuous phase of these inverse emulsions, which are prepared using membrane emulsification to control the emulsion droplet size and size distribution. Relatively monodisperse emulsions with tunable droplet size in the range of approximately 10–30 µm are prepared, followed by the RAFT polymerization step to generate polymeric microcapsules having similar size as the initial droplets. This approach will be beneficial for various applications where toxic solvents need be minimized or removed completely to avoid adverse effects. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 831–839     

Screening of the effect of surface energy of microchannels on microfluidic emulsification

We report the results of a systematic study of the effect of the surface energy of the walls of microchannels on emulsification in parallel flow-focusing microfluidic devices. We investigated the formation of water-in-oil (W/O) and oil-in-water (O/W) emulsions and found that the stability of microfluidic emulsification depends critically on the preferential wetting of the walls of the microfluidic device by the continuous phase. The condition for stable operation of the device is, however, different than that of complete wetting of the walls by the continuous phase at equilibrium. We found that W/O emulsions form when the advancing contact angle of water on the channel wall exceeds theta approximately 92 degrees. This result is unexpected because at equilibrium even for theta < 92 degrees the microchannels would be completely wet by the organic phase. The criterion for the formation of W/O emulsions (theta > 92 degrees) is thus more stringent than the equilibrium conditions. Conversely, we observed the stable formation of O/W emulsions for theta < 92 degrees, that is, when the nonequilibrium transition to complete wetting by oil takes place. These results underlie the importance of pinning and the kinetic wetting effects in microfluidic emulsification. The results suggest that the use of parallel devices can facilitate fast screening of physicochemical conditions for emulsification.     

Surfactant-free emulsions

Recent aspects and advances on surfactant-free emulsions are reviewed: preparation methods (e.g., acoustic emulsification, removal of dissolved gas from water and oil mixtures, utilization of solid particles, near- and super-critical carbon dioxide), colloidal stabilization (e.g., the addition of hydrophobic polymers into oil droplets, utilization of megasonic irradiation), and characterization techniques (single-droplet detection technique) of surfactant-free emulsions.