Encapsulation and Prolonged Release Behaviour of W/O/W Type Multiple Emulsions

W/O/W type multiple emulsions were prepared by two step emulsification procedures using an oily lymphographic agent, lipiodol, as an inner oil phase and Pluronic F-68 as a hydrophilic emulsifier contained in the outer aqueous phase. Span 80, Pluronic L-64 and HCO-60 were used as emulsifiers incorporating them into the inner oil phase. The phase volume of the inner and outer aqueous phases and the yield of the w/o/w type multiple emulsions were studied. The dissolution behaviour of the w/o/w type multiple emulsions were determined by a dialysis method employing cellulose tubing. The effect of emulsifier type and the amount of HCO-60 on the stability and prolonged release behavior of the w/o/w type multiple emulsions with or without lecithin, was also examined. The results indicate the HCO-60 is a better emulsifier than Span 80 or Pluronic L-64. Its use improves the stability and the prolonged release behavior of w/o/w type multiple emulsions.     

Influence of composition on the encapsulation properties of P/O/W multiple emulsions for Vitamin C

Abstract

The aim of this work was to study the encapsulation properties of polyols-in-oil-in-water (P/O/W) multiple emulsions for Vitamin C (Vc). The influence of formulation factors, including the concentration of lipophilic emulsifier, hydrophilic emulsifier, salt and glycerol had been investigated. The results indicated that the encapsulation stability could be improved by increasing the lipophilic emulsifier concentration which could strengthen the interfacial film. In contrast, the excess of hydrophilic emulsifier destabilized the emulsion. The presence of glycerol in the outer aqueous phase accelerated the phase transfer, thus reduced the encapsulation rate. The addition of salt in inner polyols phase had little effect on encapsulation rate while markedly affected the morphology and stability of this system. P/O/W multiple emulsions showed better encapsulation stability than the W/O/W multiple emulsions as the former’s encapsulation rate could remain more than 75% after 2?weeks while the latter only remained less than 60%. Meanwhile, the P/O/W emulsions exhibited higher storage modulus (G’), bigger loss modulus (G’’) and broaden linear viscoelastic regions than W/O/W emulsions.     

Polyols,High Pressure,and Refractive Indices Equalization for Improved Stability of W/O Emulsions for Food Applications

Mixtures of polyols (glycerol, propylene glycol, glucose) and water were emulsified in oil (isopropyl myristate (IPM), medium chain triglycerides (MCT), long chain triglycerides (LCT), and d-limonene) under elevated pressures and homogenization, in the presence of polyglycerol polyricinoleate (PGPR), glycerol monooleate (GMO), and their mixture as emulsifiers to form water-in-oil emulsions. High pressures was applied to: a) the emulsion, b) the aqueous phase and c) the oil phase in the presence of the emulsifiers (PGPR and GMO). Under optimal pressure (2000 atms) applied to the ready-made emulsion or to the aqueous phase prior to its emulsification, and with optimal composition (30wt% polyol in the aqueous phase and MCT as the oil phase), the aqueous droplets were stable for months and submicron in size (0.1 μm). Moreover, due to equalization of the oil and the aqueous phases refractive indices, the emulsions were almost transparent. Pressure and polyols have synergistic effects on the emulsions stability. During preparation, surface tensions and interfacial tensions were dramatically reduced until an optimal water/polyols ratio was achieved, which allows rupturing of the droplets to submicronal size (0.1 μm) without recoalescence and fast diffusion to the interface. These unique W/O emulsions are suitable for preparing W/O/W double emulsions for sustained release of active materials for food applications.     

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.     

Improved formulation of W/O/W multiple emulsion for insulin encapsulation. Influence of the chemical structure of insulin

W/O/W multiple emulsions are systems of potential interest in the oral administration of insulin. Although it has been shown that a single oral administration of insulin-loaded W/O/W multiple emulsion to diabetic rats led to the significant decrease of blood glucose levels (Silva Cunha et al., 1998, Int J Pharm 169:33), repeated administrations displayed unpleasant side effects such as diarrhoea and steatosis. These unwanted effects were attributed to the high oil concentration used for their preparation. In the present study, attention was focused on the reduction of oil concentration in the formulation of these systems and on the encapsulation of two different insulins. The physical properties and stability of the multiple emulsions over long periods of time were assessed by conductivity measurements, and granulometric and microscopic analyses. The encapsulation in the inner aqueous phase of two insulins, Umulin and Humalog, differing only by the transposition of one amino acid, had non-negligible effects on the formation and stability of W/O/W multiple emulsions. Both insulins were shown to improve the formation of the multiple emulsions. Circular dichroism studies and surface tension measurements evidenced the contribution of insulin conformation and surface properties in multiple emulsion formation and stability.     

Multiple emulsion stability: pressure balance and interfacial film strength

The objective of this study was to investigate the significance of inner and outer phase pressure, as well as interfacial film strength on W/O/W multiple emulsion stability using microscopy and long-term stability tests. It was observed that immediately upon applying a coverslip to samples the multiple droplets deformed and there was coalescence of the inner aqueous droplets. Under certain conditions (such as lipophilic surfactant concentration and internal phase osmotic pressure) the destabilized multiple emulsions formed unique metastable structures that had a "dimpled" appearance. The formation of these metastable structures correlated with the real-time instability of the W/O/W multiple emulsions investigated. Multiple emulsion stability also correlated with the interfacial film strength (measured by interfacial elasticity) of the hydrophobic surfactant at the mineral oil/external continuous aqueous phase interface. The formation of the metastable dimpled structures and the long-term stability of the multiple emulsions were dependent on the osmotic pressure of the inner droplets and the Laplace curvature pressure as described by the Walstra Equation (P. Walstra, "Encyclopedia of Emulsion Technology" (P. Becher, Ed.), Vol. 4. Dekker, New York, 1996). It appears that the effect of coverslip pressure on multiple emulsions may be useful as an accelerated stability testing method or for initial formulation screening.     

Preparation and characteristics of multiple emulsions containing liquid crystals

In this paper, multiple emulsions containing liquid crystals were prepared successfully and the influence of formulation parameters on the formation mechanism was studied. Moreover, differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS) spectra analysis and stability analysis were used to characterise the property of them. The results showed that the chemical structure of water-in-oil (W/O) emulsifiers directly impacted on the formation of multiple structure, but the effect on the formation of liquid crystal structure was negligible. With the gap of the polarity between inner and outer liquid oils decreased, both multiple structure and liquid crystal structure were harder to form. The content of sodium chloride in internal aqueous phase, which should be neither too high nor too low, has great impact on the formulation of multiple structure. It was easier to form two structures simultaneously when the carbon chain length of fatty alcohols was closer to that of emulsifier C₂₂ alkyl polyglucoside (202). DSC elucidated the phase transitions of water in the liquid crystal layer and the W/O emulsions. SAXS indicated that the liquid crystal orientation was lamellar. The stability analysis showed that the presence of liquid crystal structure had a significant contribution to the stability of the multiple emulsions.     

MULTIPLE EMULSIONS. PART II: PROPOSED TECHNIQUE TO OVERCOME UNPLEASANT TASTE OF DRUGS

Multiple emulsions of water in oil in water (W/O/W) have been used as a novel technique to overcome unpleasant taste of drugs. The drug is dissolved in the inner water phase and is released throughout the oil phase in the presence of synthetic gastric juice

Yield of preparation and stability have been studied using various sets of different inner (emulsifier I) and outer (emulsifier II)emulsifiers

Combination of anionic-nonionic emulsifiers yielded optimal results: High yield of preparation, high stability and complete release of the drug in synthetic gastric juice.     

W/O/W多重乳液中水传递的控制

建立了简化的W/O/W(水/油/水)多重乳液乳珠模型——统计平均半径模型, 预测出当W/O/W多重乳液内水相水滴之间以及内外水相之间均达到水传递平衡时的内外水相中盐的浓度, 从而实现对水传递的控制, 以维持W/O/W多重乳液的稳定. 按理论预测制备出了不同稳定态的W/O/W多重乳液, 利用差分扫描量热仪(DSC)检测了多重乳液中水的传递过程, 确定体系在实验状态下的稳定程度, 实验结果与理论预测基本吻合.     

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.     

Thermosensitive pickering emulsion stabilized by poly(N-isopropylacrylamide)-carrying particles

Poly(N-isopropylacrylamide) (PNIPAM)-carrying particles were characterized as thermosensitive Pickering emulsifiers. Emulsions were prepared from various oils, such as heptane, hexadecane, trichloroethylene, and toluene, with PNIPAM-carrying particles. PNIPAM-carrying particles preferentially formed oil-in-water (O/W)-type emulsions with a variety of oils. All the emulsions stabilized by PNIPAM-carrying particles were stable for more than 3 months as long as they were stored at room temperature. However, when the emulsions were heated from room temperature to 40 degrees C, at which point the PNIPAM layer caused a coil-to-globule transition, phase separation occurred. Thus, by using thermosensitive PNIPAM-carrying particles as emulsifiers, the stability of the Pickering emulsions could be controlled by a slight change in temperature.     

Stability and rheology of three types of W/O/W multiple emulsions emulsified with lecithin

Three types of multiple emulsions were prepared with lecithin. The morphology, stability, and rheological properties of the three types of W/O/W multiple emulsions were evaluated. The formulation factors, including salts and aliphatic alcohol, were further examined. The three types of multiple emulsions were formed by different emulsifiers. An excellent multiple emulsion occurred with 2?wt% lecithin concentration, stabilized by 0.05?wt% NaCl. All multiple emulsions showed shear-thinning behavior, i.e., the apparent viscosity decreased with the increase of the shear rate. With the high concentration of lecithin, the multiple emulsions exhibited the highest viscosity at low shear rate and had higher storage modulus (G′) and the loss modulus (G″). This study was conducted to reveal that different types of multiple emulsions can be formed with lecithin, and that the stability and rheological properties were different with different types of multiple emulsions.     

Formula Optimization of Emulsifiers for Preparation of Multiple Emulsions Based on Artificial Neural Networks

Formulation optimization of emulsifiers for preparing multiple emulsions was performed in respect of stability by using artificial neural network (ANN) technique. Stability of multiple emulsions was expressed by the percentage of reserved emulsion volume of freshly prepared sample after centrifugation. Individual properties of multiple emulsions such as droplet size, δ, viscosity of the primary and the multiple emulsions were also considered. A back‐propagation (BP) network was well trained with experimental data pairs and then used as an interpolating function to estimate the stability of emulsions of different formulations. It is found that using mixtures of Span 80 and Tween 80 with different mass ratio as both lipophilic and hydrophilic emulsifiers, multiple W/O/W emulsions can be prepared and the stability is sensitive to the mixed HLB numbers and concentration of the emulsifiers. By feeding ANN with 39 pairs of experimental data, the ANN is well trained and can predict the influences of several formulation variables to the immediate emulsions stability. The validation examination indicated that the immediate stability of the emulsions predicted by the ANN is in good agreement with measured values. ANN therefore could be a powerful tool for rapid screening emulsifier formulation. However, the long‐term stability of the emulsions is not good, possibly due to the variation of the HLB number of the mixed monolayers by diffusion of emulsifier molecules, but can be greatly improved by using a polymer surfactant Arlacel P135 to replace the lipophilic emulsifier.     

Quantification of unadsorbed protein and surfactant emulsifiers in oil-in-water emulsions

Unadsorbed emulsifiers affect the physical and chemical behaviour of oil-in-water (O/W) emulsions. A simple methodology to quantify unadsorbed emulsifiers in the aqueous phase of O/W emulsions has been developed. Emulsions were centrifuged and filtered to separate the aqueous phase from the oil droplets and the concentration of unadsorbed emulsifiers in the aqueous phase determined. The quantification of unadsorbed surfactants based on the direct transesterification of their fatty acids was validated for Tween 20, Tween 80, citric acid ester (Citrem), Span 20 and monolauroyl glycerol. To determine unadsorbed proteins, results obtained with Folin-Ciocalteu reagent or UV-spectrophotometry were compared on emulsions stabilized by β-lactoglobulin (BLG), β-casein (BCN) or bovine serum albumin (BSA). The first method gave more accurate results especially during aging of emulsions in oxidative conditions. The whole methodology was applied to emulsions stabilized with single or mixed emulsifiers. This approach enables optimization of emulsion formulations and could be useful to follow changes in the levels of unadsorbed emulsifiers during physical or chemical aging processes.     

Stability of W/O Emulsions Encapsulating Polysaccharides

In the frame of formulation of W/O emulsions entrapping polysaccharides devoted to agricultural applications, the aim of this work was to study the stability over time of these emulsions, stabilized with either soybean lecithin or polyglycerol polyricinoleate (PGPR) as emulsifiers. Emulsifiers were dissolved in oil phase, and polysaccharides (carboxymethycellulose (CMC), guar, xanthan) in ultrapure water. Emulsions stability was studied through natural aging tests and accelerated aging tests, using bottle tests, microscopy and calorimetry. Experiments showed that PGPR was more efficient than lecithin to stabilize emulsions containing the polysaccharides studied, and that emulsions prepared with CMC showed the best stability.     

淀粉/丙烯酸反相乳液体系的稳定性研究

以丙烯酸(AA)单体的水溶液为水相,液体石蜡为油相,失水山梨醇三油酸酯(Span 85)和辛基苯基聚氧乙烯醚(Opan 10)为复合乳化剂,合成了淀粉/丙烯酸反相乳液;考察了乳化剂亲水亲油平衡值(HLB值)、油水比、乳化剂用量、单体浓度、温度对乳液稳定性和类型的影响.结果表明,合成淀粉/丙烯酸稳定反相乳液体系的适宜条件...     

Stability versus phase ratios of geranyl acetate three-phase emulsions

Three-phase geranyl acetate emulsions stabilized by a non-ionic surfactant, Laureth 4, were prepared with a constant weight fraction of a lamellar liquid crystal and varied aqueous to oil phase weight ratios according to the phase diagram. The appearance and micrographs of the drop pattern versus time were recorded. As expected, emulsions with the lower values of the water to oil (W/O) ratio appeared to be of the W/O variety while the two more stable emulsions with the highest W/O ratio appeared as oil to water (O/W). Considering the surfactant exclusive solubility in the oil, this result was unexpected and the emulsions were investigated as to their structure. Unpredictably, all the emulsions were of the O/W kind; including the highest ratio of oil to water. The reason for this unanticipated outcome was the lamellar liquid crystal being dispersed into the aqueous phase at the slightest perturbation.     

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.     

Initial inter-phase transport of compounds in a model emulsion system

Three-phase geranyl acetate emulsions stabilized by a non-ionic surfactant, Laureth 4, were prepared with a constant weight fraction of a lamellar liquid crystal and varied aqueous to oil phase weight ratios according to the phase diagram. The appearance and micrographs of the drop pattern versus time were recorded. As expected, emulsions with the lower values of the water to oil (W/O) ratio appeared to be of the W/O variety while the two more stable emulsions with the highest W/O ratio appeared as oil to water (O/W). Considering the surfactant exclusive solubility in the oil, this result was unexpected and the emulsions were investigated as to their structure. Unpredictably, all the emulsions were of the O/W kind; including the highest ratio of oil to water. The reason for this unanticipated outcome was the lamellar liquid crystal being dispersed into the aqueous phase at the slightest perturbation.