Viability and permeability across Caco-2 cells of CBZ solubilized in fully dilutable microemulsions

The purpose of this study was to evaluate the viability and permeability of carbamazepine (CBZ) solubilized in fully dilutable non-ionic microemulsions across Caco-2 cells used as a model for intestinal epithelium. Maximum solubilization capacity (SC) of CBZ was determined within water-in-oil (W/O), bicontinuous and oil-in-water (O/W) structures formed upon dilution. The effect of the nature of the oil phase, surfactant type, and the ratio between the oil phase and surfactant on the quantity of solubilized CBZ, droplets size, the viability of the cells and drug permeability was elucidated. We found that: (1) several fully dilutable microemulsions based on pharma-grade ingredients can be loaded with very significant amounts of CBZ, (2) W/O microemulsions (10wt% water) exhibit up to 3-fold higher solubilization capacity over the drug's solubility in oil (triacetin), (3) CBZ in the O/W microemulsions (80wt% water) exhibit up to 29-fold higher solubilization than in water, (4) the O/W droplets of the examined systems are 9-11nm in size, (5) the highest permeability was obtained in systems containing triacetin/alpha-tocopherol acetate/ethanol in 3/1/4wt% ratio as oil phase and Tween 60 as surfactant, (6) the replacement of alpha-tocopherol acetate by alpha-tocopherol inhibits CBZ release, (7) replacement of a saturated chain of Tween 60 by an unsaturated (Tween 80) or shorter chain (Tween 40) inhibited drug release, (8) the decrease in the oil phase to surfactant ratio leads to enhancement of drug release (dilution line 64>dilution line 73).     

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.     

Interface composition of multiple emulsions: rheology as a probe

We have investigated the dynamic rheological properties of concentrated multiple emulsions to characterize their amphiphile composition at interfaces. Multiple emulsions (W1/O/W2) consist of water droplets (W1) dispersed into oil globules (O), which are redispersed in an external aqueous phase (W2). A small-molecule surfactant and an amphiphilic polymer were used to stabilize the inverse emulsion (W1 in oil globules) and the inverse emulsion (oil globules in W2), respectively. Rheological and interfacial tension measurements show that the polymeric surfactant adsorbed at the globule interface does not migrate to the droplet interfaces through the oil phase. This explains, at least partly, the stability improvement of multiple emulsions as polymeric surfactants are used instead of small-molecule surfactants.     

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.     

Preparation of microspheres by an emulsification-complexation method

Microspheres were prepared by complexation of a cationic polymer, polyquaternium-24, and an anionic surfactant, sodium lauryl sulfate (SLS). The cationic polymer solution was emulsified in dimethylsiloxane to give water in silicone emulsion (W/Si), and it was used as a template for the formation of microspheres. The emulsion was dispersed into the SLS solution. In this process, two kinds of droplets, silicone dropletes and microspheres composed of the cationic polymer and SLS, were formed, evidenced by X-ray energy dispersive spectra. The mean diameter of the microspheres was reduced from 105.7 to 64.8 mum as the stirring rate for W/Si preparation increased from 300 to 1000 rpm. It is believed that water droplets in W/Si emulsion, when exposed to SLS solution, could be solidified by the complexation of the cationic polymer and the anionic surfactant.     

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.     

Novel synthesis of macroporous poly(N-isopropylacrylamide) hydrogels using oil-in-water emulsions

Porous N-isopropylacrylamide (NIPA) hydrogels having a unique structure, that is, spherelike cavities distributed randomly and a homogeneous network in the gel phase, were successfully synthesized by means of an emulsion templating method; this method involves the synthesis of NIPA gels in an oil-in-water (O/W) emulsion by free radical copolymerization with a cross-linker, followed by washing (removal) of the dispersed oil as a pore template (porogen). The synthesis conditions, O/W volume ratio, amount of added surfactant, and monomer concentration affect the internal pore structure, equilibrium swelling, and swelling/shrinking kinetics. A porous hydrogel swollen at 10 degrees C has a pore diameter distribution in the range of 1-40 microm, which was observed with a scanning electron microscope. Scanning electron micrographs and swelling degree reveal that the pore size and porosity can be adjusted by varying the O/W volume ratios and surfactant amounts. The porous hydrogels show very rapid swelling/shrinking in accordance with the temperature swing. The fast response is attributed to the convection flow of water through the macropores. In addition to a faster response gel, the emulsion templating method can yield potentially intelligent gels in which the pores function as spaces for reaction, separation, and storage.     

Novel Oil‐in‐Water Emulsions Stabilised by Ionic Surfactant and Similarly Charged Nanoparticles at Very Low Concentrations

Novel oil‐in‐water (O/W) emulsions are prepared which are stabilised by a cationic surfactant in combination with similarly charged alumina nanoparticles at concentrations as low as 10^?5 m and 10^?4 wt %, respectively. The surfactant molecules adsorb at the oil‐water interface to reduce the interfacial tension and endow droplets with charge ensuring electrical repulsion between them, whereas the charged particles are dispersed in the aqueous films between droplets retaining thick lamellae, reducing water drainage and hindering flocculation and coalescence of droplets. This stabilization mechanism is universal as it occurs with different oils (alkanes, aromatic hydrocarbons and triglycerides) and in mixtures of anionic surfactant and negatively charged nanoparticles. Further, such emulsions can be switched between stable and unstable by addition of an equimolar amount of oppositely charged surfactant which forms ion pairs with the original surfactant destroying the repulsion between droplets.     

分散体系形成中表面活性剂使用量的判据

通过对甲苯等有机溶剂/水/表面活性剂体系的水基化分散,利用MalvernMicroplus型激光粒度仪对乳化后的分散相粒子大小及其分布进行研究.结果表明,表面活性剂的使用量对分散结果的影响具有局限性,对于具体体系,表面活性剂的临界胶束浓度[CMC(CMC_O+CMC_W)是这种局限性的量化标志,超出CMC的表面活性剂是多余的,对最终的分散结果无作用,同时也会影响分散体系的稳定性.     

Characterization of fluorocarbon-in-water emulsions with added triglyceride

Fluorocarbon-in-water emulsions are being explored clinically as synthetic oxygen carriers in general surgery. Stabilizing fluorocarbon emulsions against coarsening is critical in maintaining the biocompatibility of the formulation following intravenous administration. It has been purported that the addition of a small percentage of long-chain triglyceride results in stabilization of fluorocarbon emulsions via formation of a three-phase emulsion. In a three-phase emulsion, the triglyceride forms a layer around the dispersed fluorocarbon, thereby improving the adhesion of the phospholipid surfactant to the dispersed phase. In the present study, we examined the effect of triglyceride addition on the physicochemical characteristics of the resulting complex dispersion. In particular, we examined the particle composition and stability of the dispersed particles using a method which first fractionates (classifies) the different particles prior to sizing (i.e., sedimentation field-flow fractionation). It was determined that the addition of a long-chain triglyceride (soybean oil) results in oil demixing and two distinct populations of emulsion droplets. The presence of the two types of emulsion droplets is not observed via light scattering techniques, since the triglyceride droplets dominate the scattering due to a large difference in the refractive index between the particles and the medium as compared to fluorocarbon droplets. The growth of the fractionated fluorocarbon emulsion droplets was followed over time, and it was found that there was no difference in growth rates with and without added triglyceride. In contrast, addition of medium-chain-triglyceride (MCT) oils results in a single population of emulsion droplets (i.e., a three-phase emulsion). These emulsions are not stable to droplet coalescence, however, as significant penetration of MCT into the phospholipid lipid interfacial layer results in a negative increment in the monolayer spontaneous curvature, thereby favoring water-in-oil emulsions and resulting in destabilization of the emulsion to the effects of terminal heat sterilization or mechanical stress.     

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.     

Phase inversion of the Pickering emulsions stabilized by plate-shaped clay particles

We investigated the phase inversion of Pickering emulsions stabilized by plate-shaped clay particles. Addition of water induced a phase inversion from a water-in-oil (W/O) emulsion to an oil-in-water (O/W) emulsion when the amount of the oil phase exceeded a limiting amount of oil absorption to solid particles. On the other hand, a phase inversion from a powdery state to an O/W emulsion state through an oil-separated state is observed when the amount of an oil phase is less than the limiting amount of the oil absorption. Interestingly, the oil separated is re-dispersed as emulsion droplets into the O/W emulsion phase. This type of phase inversion, which is a feature of the Pickering emulsions stabilized by the clay particles, is caused by a change in the aggregate structures of particles.     

DEMULSIFICATION OF WATER IN OIL EMULSIONS USING WATER SOLUBLE DEMULSIFIERS

The possibility of using a water soluble,as opposed to the conventional oil soluble demulsifier, to destabilize a w/o emulsion in crude oil has been explored. It was found experimentally that a surfactant soluble in the water (dispersed) phase could destabilize the emulsion. Polymer molecules with varying HLB's and molecular weights and structure were synthesized and these compounds were added to the water phase to destabilize the water/crude oil emulsions. Molecules with a high percentage of hydrophilic groups and low molecular weights showed very good demulsifying abilities.     

Molecular Dynamics Simulation for the Demulsification of O/W Emulsion under Pulsed Electric Field

A bidirectional pulsed electric field (BPEF) method is considered a simple and novel technique to demulsify O/W emulsions. In this paper, molecular dynamics simulation was used to investigate the transformation and aggregation behavior of oil droplets in O/W emulsion under BPEF. Then, the effect of surfactant (sodium dodecyl sulfate, SDS) on the demulsification of O/W emulsion was investigated. The simulation results showed that the oil droplets transformed and moved along the direction of the electric field. SDS molecules can shorten the aggregation time of oil droplets in O/W emulsion. The electrostatic potential distribution on the surface of the oil droplet, the elongation length of the oil droplets, and the mean square displacement (MSD) of SDS and asphaltene molecules under an electric field were calculated to explain the aggregation of oil droplets under the simulated pulsed electric field. The simulation also showed that the two oil droplets with opposite charges have no obvious effect on the aggregation of the oil droplets. However, van der Waals interactions between oil droplets was the main factor in the aggregation.     

Retardation of crystallization-induced destabilization of PMF-in-water emulsion with emulsifier additives

An oil-in-water (O/W) emulsion, in which the oil phase is semi-solid fat, is easily destabilized when stored below the crystallization temperature of the oil phase. Such destabilization, characterized by loss of fluidity at chilled temperature and oil-water separation after re-heating, is caused by inter-droplet bridging of fat crystals protruding out of the emulsion droplets. In the present study, we found that the simultaneous use of additives of highly hydrophobic sucrose oligoester (SOE; P-170) and highly hydrophilic SOE (P-1670) containing palmitic acid moiety remarkably retarded the crystallization-induced destabilization of the O/W emulsion that contains palm-mid-fraction (PMF) as the oil phase. Without the additives, destabilization occurred when the emulsion was cooled from 60 to 0 degrees C and kept at 0 degrees C for 1 day. Microscopic observation revealed that destabilization was caused by coalescence of the oil droplets, which was triggered by the growth of needle-shaped PMF crystals protruding out of the emulsion membranes. However, the addition of P-170 to PMF increased the crystallization temperature of PMF and at the same time retarded the destabilization. Furthermore, the simultaneous addition of P-170 and P-1670 retarded the crystallization-induced destabilization even more. Optical observation, DSC, and synchrotron radiation X-ray diffraction measurements indicated that the P-170 additive enhanced interfacial heterogeneous crystallization to form tiny PMF crystals in the droplets, and that the P-1670 additive retarded morphological change of the PMF crystals into long needle shapes in association with polymorphic transformation from alpha to beta'.     

Influence of pH on the stability of oil-in-water emulsions stabilized by a splittable surfactant

A laboratory study was conducted to evaluate the effect of pH on the stability of oil-in-water emulsions stabilized by a commercial splittable surfactant Triton SP-190 by comparison with the results obtained by a common surfactant Triton X-100. The emulsion stability was explored by measuring the volume of oil phase separated and the size of the dispersed droplets. It was found that the addition of inorganic acids did not significantly affect the stability of emulsions stabilized by Triton X-100, but had a profound influence on the stability of emulsions stabilized by Triton SP-190. Moreover, the droplet size of a Triton X-100-stabilized emulsion and its dynamic interfacial activity were insensitive to acids. However, at lower pH the droplet size of the emulsions stabilized by Triton SP-190 was considerably increased. From the dynamic interfacial tension measurements the dynamic interfacial activity of Triton SP-190 at the oil/water interface was found to be strongly inhibited by the addition of acids, resulting in a slower decreasing rate of dynamic interfacial tension. The results demonstrate that the dramatic destabilization of Triton SP-190-stabilized emulsions could be realized by the use of acids, which evidently changed the interfacial properties of the surfactant and resulted in a higher coalescence rate of oil droplets.     

Extension of the Taylor Equation for Oil-Water-Surfactant System and Investigating the Impact of Surfactant Concentration over the Quality of Emulsion

Emulsions stand among the most important multiphase fluids, exhibiting various complicated phenomenon. To understand the process of emulsification, the Taylor equation has been extended to incorporate the parameters that depend on molecular mass of oil and their contents and the amount of surfactant added. To test the validity of the proposed equations, four well-defined short chain (n-hexane, n-heptane, n-decane, and kerosene) oils were emulsified in water and the results were compared with the experimental ones. It has been concluded that the extended Taylor equation worked well, even in the presence of surfactant. The quality of the emulsion defined and discussed in terms of size and number of droplets was best near CMC of the surfactant used. A relationship has also been derived between CMC of surfactant and its distribution coefficient, which allows the exact value of one parameter to be determined if other is known.     

Flocculation and Coalescence of Oil-in-Water Poly(dimethylsiloxane) Emulsions

The stability of poly(dimethylsiloxane) (PDMS) oil-in-water emulsions has been investigated in the presence of added NaCl as well as in the presence of added surfactant. The emulsions were prepared using a combination of nonionic (C(x)E(y), x and y represent the number of methylene (C) and ethylene oxide (E) groups, respectively) and cationic (quarternary alkylammonium) surfactants. The droplets were observed to exhibit weak flocculation in the presence of high NaCl concentration (1 M). Phase separation and optical microscopic observations revealed that the principal mechanism for emulsion destabilization at high salt concentration was coalescence, which was accelerated at elevated temperature (50 degrees C). The effective coalescence rate for diluted emulsions was investigated using photon correlation spectroscopy. The small effective Hamaker constant for PDMS is the primary reason for the slow rate of coalescence observed for the emulsions at neutral pH in the presence of NaCl. The stability of PDMS emulsions to flocculation is qualitatively similar to that reported for low Hamaker constant dispersions (e.g., microgel particles). Addition of cationic surfactants (cetyltrimethylammonium chloride and dodecyl dimethylbenzylammonium chloride) to the negatively charged droplets after preparation was shown to decrease the emulsion stability once the surfactant concentration exceeded the CMC. Electrophoretic mobility measurements showed that added cationic surfactant changed the sign of the droplet charge from negative to positive at concentrations well below the CMC. Charged micelles of the same sign as the droplets are electrostatically excluded from close approach to the droplet surface within a distance (varepsilon) which results in depletion flocculation. Copyright 2000 Academic Press.     

Preparation of Y2O3 nanoparticulate thin films using an emulsion liquid membrane system

Y2O3 nanoparticulate thin films have been prepared using an emulsion liquid membrane (water-in-oil-in-water (W/O/W) emulsion) system, consisting of Span 83 (sorbitan sesquioleate) as a surfactant and VA-10 (2-methyl-2-ethylheptanoic acid) as an extractant (cation carrier). Yttrium ions were extracted from the external water phase and stripped into the internal water phase to make precursor oxalate nanoparticles. Y2O3 nanoparticulate thin film was prepared by casting the W/O emulsion, separated from the external phase and containing the Y oxalate nanoparticles, on a Si substrate, followed by calcination in air. Well-arranged thin-layer nanoparticulate film, consisting of Y2O3 nanoparticles smaller than 20 nm, was obtained via spin coating of the W/O emulsion. A multilayer nanoparticulate thin film was also fabricated via a simple procedure of repeated coating and subsequent calcination.     

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.