Stability Of Multiple Emulsions Research Articles

Formulation and Evaluation of Multiple Emulation of Diclofenac Sodium

Abstract: Multiple emulsion is novel approach of drug delivery system for enhancement of bioavailability and pharmacological activity. It is important to prevent the problem of oral drugdelivery system and they are stabilized by using of combination of hydrophilic and lipophilic surfactant. The specific ratio of surfactant concentration is responsible for maintaining the stability of multiple emulsions, the importance of this study was to prepare multiple emulsion of Diclofenac sodium by using two step emulsification process, by using the non-ionic surfactant units. In multiple emulsion, the stability of multiple emulsion was evaluated, percent entrapment efficiency as well as in vitro studies are conducted. The objective of this study was to prepare multiple emulsion of Valsartan by two step emulsification using different nonionic surfactants, Tweens & Spans, and evaluate for stability,percentage drug entrapment, in vitro drug release.

Physico-Chemical Study of Curcumin and Its Application in O/W/O Multiple Emulsion.

Curcuma is a world-renowned herb known for its immense health benefits. In this study, physicochemical analyses were performed on the curcumin standard sample and curcumin multiple emulsions. The emulsions were analysed for thermal and structural stability for 21 days. Confocal laser microscopy (CLSM) was performed in order to observe the emulsion encapsulation. Modulated differential scanning calorimetry (MDSC) and HPLC methods revealed a variety of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin) in the investigated curcumin standard. In addition, the MDSC method was found to be suitable and comparable to HPLC for determining the curcuminoid substances. The analysis of the curcumin release revealed a value of 0.18 w.% after 14 days as the equilibrium value. Furthermore, an increase in the sizes of the emulsions was observed at the end of the 21-day study. The emulsion stability index (ESI) was used to measure the stability of multiple emulsions. The ESI reached 55.8% between 7 and 21 days later. Nano droplets of the oil phase loaded with dispersed curcumin particles captured inside the water-based carboxymethylcellulose micelles were clearly observed by CLSM.

Multiple Pickering emulsions stabilized by the same particles with different extent of hydrophobization in situ.

Multiple emulsions are widely used in pharmaceuticals, foods, and cosmetics. However, those stabilized by surfactants with different HLB values are generally unstable due to the diffusion of the surfactants between inner and outer interfaces. Here, we report that multiple W/O/W emulsions can be prepared by using the same particles in combination with a surfactant of different concentrations. The less surface-active raw CaCO3 nanoparticles can be hydrophobized to surface-active in situ by adsorption of the anionic surfactant SDS, and the wettability of the particles can be controlled to be suitable for stabilizing both O/W and W/O Pickering emulsions by adjusting the surfactant concentration. With toluene as oil phase, the CaCO3 particles at 1.0 wt% tend to stabilize a W/O emulsion in the presence of 3 mm SDS in an aqueous solution, which can then be further dispersed in an aqueous phase with 1.0 wt% CaCO3 and SDS below 1 mm to form a W/O/W multiple emulsion. The effects of the ratio of W/O emulsion to the outer water phase and the preparation methods on stabilization of multiple emulsions were examined. With a ratio smaller than 3:1 and by gentle magnetic stirring, the multiple emulsions obtained can stay stable for at least a month without coalescence. This simple method not only ensures stabilization of multiple emulsions but also avoids complicated synthesis of colloid particles with different wettability.

An Overview on Multiple Emulsions

Multiple emulsions are dynamic hetero-dispersed structures in which water concurrently occurs water in oil and oil in water emulsion both controlled by lipophillic and hydrophilic surfactants. The combination of all such surfactants is useful in stabilizing multiple emulsions. Multiple emulsions include water-in-oil-in-water (w / o / w) and oil-in-water-in-oil (o / w / o) type; the former has extensive formulation, preparation techniques, and multiple-emulsion in-vitro analysis methods are checked. With specific reference to multiple emulsions of the w / o / w, different factors influencing the stability of multiple emulsions and stabilize strategies are discussed in detail. It finds wide range of applications in Multiple emulsions in cancer therapy, Multiple emulsions in herbal medicines, Vaccine / adjuvant, Oxygen replacement, Inverse targeting, Multiple diabetes emulsions, Multiple emulsions in food, Drug over doses treatment, etc. In the course of such microencapsulation a few emulsions were also used as an intermediate step in the process of such microencapsulation and are the structures of growing interest in the oral delivery of hydrophilic drugs that become unstable in gastrointestinal tracts such as proteins and peptides. Stability a with developing preparation methods, drug release tests, in vitro release studies, globule size or particle size, stability and rheological characterization of multiple emulsions, will be able to provide a novel carrier mechanism for medicines, cosmetics and pharmaceutical agents.

Stability of multiple emulsions under shear stress

Multiple liquid emulsions of the water in oil in water (W1/O/W2) type are used in a variety of consumer or technical applications, for instance in the encapsulation of certain active ingredients. The encapsulation process and release mechanisms of the inner phase of the carrier drops are important in order to properly process and formulate such liquid‐liquid systems. In this work the stability and breakage of multiple W1/O/W2 emulsions under mechanical shear stress are investigated for emulsions with different surfactants and surfactant concentrations of the internal emulsion. Stressing the emulsions in a mechanical stirring process is compared to the membrane emulsification process. The membrane emulsification process results in higher encapsulation efficiencies than the stirring process. The emulsion droplets were subjected to shear stress below and above the critical capillary number for drop breakup. The results show that stable inner emulsions with sufficient surfactant concentrations increase the overall encapsulation efficiency for multiple emulsions subjected to shear stress, although the effect is not prominent. The depletion of the carrier oil droplets could be achieved for Ca numbers below the critical limit, reducing the encapsulation efficiency below 10 %. This shows that even a low shear stress can result in content release from the internal droplet phase. The experimental emulsion release study is supported by a numerical simulation of drop deformation and break‐up under shear stress.

Influence of particle concentration on multiple droplet formation in Pickering emulsions

HypothesisMultiphase droplets form when oil and water are mixed together at the ambivalent conditions that occur close to phase inversion. In this paper we propose a mechanism for the stabilisation of multiphase droplets by a single population of particles. ExperimentsWe investigated the microstructure of emulsions formed when dodecane and water are mixed in the presence of hydrophobic fumed silica nanoparticles. We identified the range of compositions, mixing times and rates where water-in-oil-in-water emulsions are stabilised in a single mixing step. To explore how the particle availability and mixing conditions lead to multiple emulsion formation we used light scattering and microscopy techniques to probe the size and morphology of the drops, and the particle coverage of the interfaces. FindingsOur key finding is that to stabilise multiphase drops there should be sufficient particles available to coat water drops that are entrained within coalescing oil droplets. The size of an entrained drop is determined by the volume of the rupturing film that forms between the oil drops. The particle coating prevents the entrained drop from escaping into the external aqueous phase. These results suggest a simple route for controlling the formation and stability of multiple emulsions for encapsulation applications.

Microencapsulation of betanin in monodisperse W/O/W emulsions

Betanin is the main pigment of the food color beetroot red (E162). Due to the fair heat and light stability of E162, this pigment is mainly used in minimally processed packaged food products. Encapsulation increases the stability of betanin, but detailing on the effect of different sources of betanin on the properties and stability of multiple emulsions are scarce. Here we describe the encapsulation of E162, spray-dried beetroot juice and betanin in a monodisperse food-grade water-in-oil-in-water (W/O/W) emulsions by using microchannel emulsification. We compare the tinctorial strength of the encapsulated pigments and investigate the effect of temperature, storage period and pigment concentration on emulsion stability and color. Betanin increases the overall stability of the W/O/W emulsion, reduce the oil droplet size and improve size distribution when compared to the negative control without pigment and to emulsions containing betanin from other sources.

Multiple Water-in-Oil-in-Water Emulsion Gels Based on Self-Assembled Saponin Fibrillar Network for Photosensitive Cargo Protection.

A gelled multiple water-in-oil-in-water (W1/O/W2) emulsion was successfully developed by the unique combination of emulsifying and gelation properties of natural glycyrrhizic acid (GA) nanofibrils, assembling into a fibrillar hydrogel network in the continuous phase. The multiple emulsion gels had relatively homogeneous size distribution, high yield (85.6-92.5%), and superior storage stability. The multilayer interfacial fibril shell and the GA fibrillar hydrogel in bulk can effectively protect the double emulsion droplets against flocculation, creaming, and coalescence, thus contributing to the multiple emulsion stability. Particularly, the highly viscoelastic bulk hydrogel had a high storage modulus, which was found to be able to strongly prevent the osmotic-driven water diffusion from the internal water droplets to the external water phase. We show that these multicompartmentalized emulsion gels can be used to encapsulate and protect photosensitive water-soluble cargos by loading them into the internal water droplets. These stable multiple emulsion gels based on natural, sustainable saponin nanofibrils have potential applications in the food, pharmaceutical, and personal care industries.

Innovative applications of food-related emulsions

ABSTRACTResearch on oxidative stability of multiple emulsions is very scarce. Given that this is a relevant topic that must be ascertained before the successful application of multiple emulsions in foods (especially when a combination of highly unsaturated oils is used as a lipid phase), this review mainly focuses on various aspects of the multiple emulsions.Fat replacement in meat products using emulsions is critically discussed along with innovative applications of natural antioxidants in food-based emulsions and multiple emulsions based on bioactive compounds/encapsulation as well as confectionery products.

New strategy of multiple emulsion formation based on the interactions between polymeric emulsifier and natural ingredients

Intensive studies have been conducted to determine biological activities of emulsions containing herbal extracts, but the effect of the extracts on technological characteristics of the emulsion system is poorly investigated. So the aim of our study was to determine the role of Rosmarinus officinalis L., Linum usitatissimum L., Avena sativa L. extracts and their interactions with polymeric emulsifier in the formation and stability of multiple emulsion. Herbal ingredient combinations were modified according to the experimental design matrix. The technological parameters of all the preparations were evaluated using centrifugation and conductivity tests, microscopic and viscometric analysis. A new approach to the formation of multiple emulsion has been taken by using an ethanolic rosemary extract in the presence of polymeric emulsifier. A direct, requiring no additional technological stages, emulsification process was established using herbal ingredients only. The different compositions revealed that all the plant extracts markedly affected rheological properties and stability of multiple emulsion. Weak herbal gels of linseed and oat groats were investigated and used as alternative additives to enhance stability of the emulsion. The prototype of potential w/o/w type drug delivery system was successfully created on the basis of natural ingredients using mixture design as an optimization tool.

Influence of Processing on the Physical Stability of Multiple Emulsions Containing a Green Solvent

AbstractThe influence of the emulsification process on the microstructure and physical stability of model water‐in‐oil‐in‐water (W/O/W) emulsions formulated with a green solvent and a mixture of amphiphilic copolymers as emulsifiers was investigated. Emulsions were prepared by applying a homogenization step with a rotor‐stator device followed by high‐pressure homogenization. Viscous flow tests, transmitted light optical microscopy, globule size distribution (GSD), and multiple light scattering (MLS) measurements were carried out. The GSDs obtained were the result of a recoalescence due to overprocessing and the coalescence of inner droplets with the outer water phase. MLS detected a main destabilization mechanism by creaming. The passing of the emulsion through a high‐pressure homogenizer (HPH) significantly delayed the creaming process.

Cellulose nanofibrils for one-step stabilization of multiple emulsions (W/O/W) based on soybean oil

Cellulose nanofibrils (CNF) were incorporated in water-in-oil (W/O) microemulsions and emulsions, as well as water-in-oil-in-water (W/O/W) multiple emulsions using soybean oil. The addition of CNF to the aqueous phase expanded the composition range to obtain W/O/W emulsions. CNF also increased the viscosity of the continuous phase and reduced the drop size both of which increased the stability and effective viscosity of the emulsions. The effects of oil type and polarity on the properties of the W/O/W emulsions were tested with limonene and octane, which compared to soybean oil produced a smaller emulsion drop size, and thus a higher emulsion viscosity. Overall, CNF are a feasible alternative to conventional polysaccharides as stability enhancers for normal and multiple emulsions that exhibit strong shear thinning behavior.

Preliminary 1 month stability screening of cosmetic multiple emulsions (W/O/W) prepared using cetyl dimethicone copolyol and Polysorbate 80.

The objective of this work was to develop W/O/W emulsions with different concentration of paraffin oil, lipophilic (cetyl dimethicone copolyol) and hydrophilic emulsifiers (polysorbate 80) and to check their stability at different storage conditions. Approximately, 20 formulations (W/O/W) multiple emulsions were prepared, and their stability was checked at different storage conditions for the period of 30days. Stability of some multiple emulsions ME12, ME13, ME14, ME19 and ME20 was also checked with carbomer as viscosity-enhancing agent. Microscopic analysis for droplet size determination and rheological characterization of most stable multiple emulsions, that is, ME20 were also performed. It was observed that stability of multiple emulsion increases with the addition of gelling agent. Formulation (ME20) with 13.6% paraffin oil, 2.4% cetyl dimethicone copolyol and 0.8% polysorbate 80 was found more stable at 25°C and 40°C for the period of 30 days. Rheological analysis indicated a decrease in viscosity with the passage of time, while droplet size analysis indicated an increase in droplet size with the passage of time. As a conclusion of this work, a stable multiple emulsion with 13.6% paraffin oil, 2.4% cetyl dimethicone copolyol and 0.8% polysorbate 80 can be formulated and can be further studied for any active ingredient for cosmetic purposes.

Comparative study of the stability of multiple emulsions containing a gelled or aqueous internal phase

Water in Oil in Water (WOW) multiple emulsions have, for many years, been studied in order to utilise their functionality in food and pharmaceuticals, for reduced fat formulation, drug delivery and taste masking applications. However, their complex structure is susceptible to a broader range of instabilities than conventional emulsions. In this study we investigate the role of different emulsifiers and a simple, novel approach to gel the internal aqueous droplets to improve the stability to heat, shear, and the presence of salt. Changes in salt concentration can be detrimental to multiple emulsions, as this will induce swelling or shrinkage of the internal water droplets. Polyglycerolpolyricinoleate (PGPR) was the preferred low HLB emulsifier, and its presence dominated the stability of the WOW emulsions, irrespective of the high HLB emulsifier. However, lecithin was found to be the most stable high HLB emulsifier to heating. Gelling the internal water droplets with either alginate or carrageenan reduced the size of the water droplets, probably due to reduced recoalescence rates. The multiple Gel in Oil in Water (GOW) emulsions were more stable to the addition of up to 1 wt% salt to the external phase than WOW emulsions. In addition, the presence of xanthan in the external phase further improved the stability to the addition of salt. Therefore GOW emulsions show potential to be used in a realistic food processing environment, showing stability to shear, temperature and changes in salt concentration.

Influence of asymmetric ratio of amphiphilic diblock copolymers on one-step formation and stability of multiple emulsions

Multiple emulsions have attracted significant interests for fundamental study and practical applications. However, the preparation of stable multiple emulsions is difficult in general because the emulsification often involves a two-step process as well as two kinds of surfactants are needed to stabilize the two thermodynamically unstable interfaces. Recently, we described a one-step inversion approach for fabricating multiple emulsions with long-term stability by using a precisely defined amphiphilic copolymer, poly(ethylene glycol)-b-polystyrene (PEG-b-PS), as sole surfactant. Herein we examine the correlation of the nature of this block copolymer with its emulsification performance in more details. Our result shows that the asymmetric ratio, namely the ratio of block length between PS and PEG of the synthesized diblock copolymer, has a great influence on the catastrophic phase inversion as well as the type and stability of the resulting emulsions. The symmetric block copolymer with the asymmetric value close to 1 can lead to stable multiple emulsions because they might have the highest surface covering density not only at the oil-in-water (O/W) normal emulsion interface, but also at the water-in-oil (W/O) inverse emulsion interface. For highly asymmetric block copolymer like PEG45-b-PS150, only W/O emulsion is obtained as the longer PS block will increase the hydrophobicity of the polymer and then it will be preferentially wetted by oil. However, for asymmetric PEG45-b-PS6 block copolymer with shorter PS block, it leads to very different catastrophic phase inversion depending on whether the micelles are formed in the aqueous phase.

Interfacial film stabilized W/O/W nano multiple emulsions loaded with green tea and lotus extracts: systematic characterization of physicochemical properties and shelf-storage stability.

Background and aimsMultiple emulsions have excellent encapsulating potential and this investigation has been aimed to encapsulate two different plant extracts as functional cosmetic agents in the W/O/W multiple emulsions and the resultant system’s long term stability has been determined in the presence of a thickener, hydroxypropyl methylcellulose (HPMC).MethodsMultiple W/O/W emulsions have been generated using cetyl dimethicone copolyol as lipophilic emulsifier and a blend of polyoxyethylene (20) cetyl ether and cetomacrogol 1000® as hydrophilic emulsifiers. The generated multiple emulsions have been characterized with conductivity, pH, microscopic analysis, phase separation and rheology for a period of 30 days. Moreover, long term shelf-storage stability has been tested to understand the shelf-life by keeping the generated multiple emulsion formulations at 25 ± 10°C and at 40 ± 10% relative humidity for a period of 12 months.ResultsIt has been observed that the hydrophilic emulsifiers and HPMC have considerably improved the stability of multiple emulsions for the followed period of 12 months at different storage conditions. These multiple emulsions have shown improved entrapment efficiencies concluded on the release rate of conductometric tracer entrapped in the inner aqueous phase of the multiple emulsions.ConclusionMultiple emulsions have been found to be stable for a longer period of time with promising characteristics. Hence, stable multiple emulsions loaded with green tea and lotus extracts could be explored for their cosmetic benefits.

Design and development of multiple emulsion for enhancement of oral bioavailability of acyclovir

The objective of this investigation was to design and develop water-in-oil-in-water type multiple emulsions (w/o/w emulsions) entrapping acyclovir for improving its oral bioavailability. Multiple emulsions (MEs) were prepared and optimized using Span-80 and Span-83 as lipophilic surfactant and Brij-35 as hydrophilic surfactant. The physio-chemical properties of the w/o/w emulsions - particle size, viscosity, phase separation (centrifugation test) and entrapment efficiency were measured and evaluated along with macroscopic and microscopic observations to confirm multiple nature, homogeneity and globule size. Stability study, in vitro and ex vivo release studies were performed followed by in vivo studies in rats. Stable w/o/w emulsions with a particle size of 33.098 ± 2.985 µm and 85.25 ± 4.865% entrapment efficiency were obtained. Stability studies showed that the concentration of lipophilic surfactant was very important for stability of MEs. Drug release from the prepared formulations showed initial rapid release followed by a much slower release. In vivo studies in rats indicated prolonged release and better oral bioavailability as compared to drug solution. The overall results of this study show the potential of the w/o/w emulsions as promising drug delivery systems for acyclovir.

Stability of a Cosmetic Multiple Emulsion Loaded with Green Tea Extract

Multiple emulsions are excellent and exciting potential systems for the delivery of useful cosmetic agents. The work describes stability of a multiple emulsion for cosmetic purpose, loaded with extract of Camellia sinensis L. (Theaceae) in concentration of 5%. The formulation constitutes of cetyl dimethicone copolyol and polyoxyethylene (20) cetyl ether as emulsifiers and was characterised and monitored for various physicochemical aspects. Centrifugation has no devastating effect on physical destabilization/phase separation observed for 30 days. Mean globule sizes of multiple droplets were found in the range of 10.29 ± 4.4 μm to 12.77 ± 5.1 μm and of inner droplets were in the range of 0.8 ± 0.4 μm to 1.6 ± 0.8 μm. All samples exhibited shear thinning behavior with increase in shear stress. The results of the present study indicate that multiple emulsions can be used as carrier of 5% Camellia sinensis L. extract to enhance desired effects. The developed physically and chemically stable system is an effective system for targeting skin layers; however, long-term stability at elevated temperatures may be needed with suitable modifications, if required.

Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions

Three multiple water-in-oil-in-water (W/O/W) nanoemulsions have been designed for potential inclusion of either lipophilic or hydrophilic drugs using a two-step emulsification process exclusively based on low-energy self-emulsification. The W/O primary emulsion was constituted by a blend of oil (medium chain triglyceride), a mixture (7:3) of two surfactants, and a 10% water phase. The surfactants were a mixture of Polysorbate-85/Labrasol®, Polysorbate-85/Cremophor® EL or glycerol/Polysorbate-85. The final W/O/W nanoemulsions were obtained by the addition of water, with a weight ratio nanoemulsion/water of 1:2. The multiple emulsion stability was found to increase from 24 hours to 2 and 6 months with Labrasol, glycerol, and Cremophor, respectively. Cytotoxicity was found for formulations including Labrasol and Cremophor EL. The concentration of emulsion inhibiting 50% cell viability (IC50) was determined using the alamarBlue® test, giving after 24 hours of incubation, IC50 = 10.2 mg/mL for the Labrasol formulation and IC50 = 11.8 mg/mL for the Cremophor EL formulation. Corresponding calculated IC50 values for surfactants were 0.51 mg/mL for Labrasol and 0.59 mg/mL for Cremophor EL. In both cases, cytotoxicity was due to an apoptotic mechanism, evidenced by chromatin condensation and P2X7 cell death receptor activation. The formulation including glycerol, investigated between 1 and 100 mg/mL concentration of nanoemulsion, did not affect cell viability. Moreover, neither chromatin condensation nor P2X7 activation was found between the 10 and 30 mg/mL final concentration of the emulsion. This last formulation would therefore be of major interest for further developments.

Stability of Anthocyanin‐Rich W/O/W‐Emulsions Designed for Intestinal Release in Gastrointestinal Environment

Anthocyanins belong to the most important hydrophilic plant pigments. Outside their natural environment, these molecules are extremely unstable. Encapsulating them in submicron-sized containers is one possibility to stabilize them for the use in bioactivity studies or functional foods. The containers have to be designed for a target release in the human gastrointestinal system. In this contribution, an anthocyanin-rich bilberry extract was encapsulated in the inner aqueous phase of water-in-oil-in-water-double emulsions. The physical stability as well as the release of free fatty acids and encapsulated, bioactive substances from the emulsions during an in vitro gastrointestinal passage were investigated. The focus was on the influence of emulsion microstructural parameters (for example, inner and outer droplet size, disperse phase content) and required additives (emulsifier systems), respectively. It could be shown that it is possible to stabilize anthocyanins in the inner phase of double emulsions. The release rate of free fatty acids during incubation was independent of the emulsifier used. However, the exterior (O/W)-emulsifier has an impact on the stability of multiple emulsions in gastrointestinal environment and, thus, the location of release. Long-chained emulsifiers like whey proteins are most suitable to transport a maximum amount of bioactive substances to the effective location, being the small intestine for anthocyanins. In addition, it was shown that the dominating release mechanism for entrapped matter was coalescence of the interior W(1) -droplets with the surrounding W(2) -phase.