Review
Preparation of double emulsions by membrane emulsification—a review

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Abstract

Double emulsions have potential for the production of low calorie food products, encapsulation of medicines and other high value products. The main issue is the difficulty to efficiently produce double emulsions in a well controlled manner due to their shear sensitivity. In membrane emulsification only mild shear stresses are applied and it is therefore expected that this process is very suitable for the production of double emulsions. In this review an overview is given of the state of the art; the advantages and disadvantages of membrane emulsification in relation to the production of stable double emulsions are summarized and compared. Finally an outlook on further research in this field is given.

Introduction

Double emulsions have promising applications in the food industry (low calorie products, improved sensoric characteristics, taste-masking), cosmetic industry (easily spreadable creams with encapsulated ingredients in both water and oil phases), pharmaceutical industry (drug delivery systems) and other fields like agriculture and the production of multicompartment microspheres. Although a certain measure of ‘controlled instability’ is desired in some cases, such as for a drug delivery system, in general the stability of double emulsions is low and poorly controllable and therefore a main problem with regard to shelf life of a product. The instability usually leads to a significant part of the internal phase being lost already during the production of the double emulsion.

The first paper on double emulsions dates back 80 years [1], but there are still many challenges left for effective production of stable double emulsions. Control of shear forces is one of the main issues that may be within reach of a relatively new production method: membrane emulsification.

In this review we briefly touch upon the production of single emulsions in order to introduce some basic concepts, but mainly focus on the production of double emulsions. Various emulsification methods such as rotor stator systems, high-pressure homogenizers and obviously membrane emulsification and other membrane-based methods are discussed and compared in Section 2. The role of surfactants is highlighted in Section 3 after which application areas of double emulsions are discussed (Section 4). The paper rounds off with an outlook on the future of various aspects related to membrane emulsification and membrane-based techniques (Section 5).

Emulsions are dispersed, multiphase systems consisting of at least two insoluble liquids [2]. The dispersed phase is present in the form of droplets in a continuous phase. Depending on the emulsification process, the diameter of the droplets lies between 0.1 μm and 0.1 mm. Emulsions of this kind are thermodynamically unstable, which means that there is a tendency to reduce the interface (as a result of a relatively high interfacial tension), causing the droplets to coalesce and therewith decreasing the total amount of interface.

A double emulsion is an emulsion in an emulsion. Two main types of double emulsions can be distinguished: water-in-oil-in-water (W/O/W) emulsions, in which a W/O emulsion is dispersed as droplets in an aqueous phase, and oil-in-water-in-oil (O/W/O) emulsions, in which an O/W emulsion is dispersed in an oil phase. W/O/W emulsions are more common than O/W/O emulsions. Double emulsions contain more interface and are even more thermodynamically unstable than single emulsions.

Usually double emulsions are prepared in a two-step emulsification process (see Fig. 1) using two surfactants; a hydrophobic one designed to stabilize the interface of the W/O internal emulsion and a hydrophilic one for the external interface of the oil globules (for W/O/W emulsions). The primary W/O emulsion is prepared under high-shear conditions to obtain small droplets while the secondary emulsification step is carried out with less shear to avoid rupture of the internal droplets [3]. In conventional emulsification processes high-shear stresses are needed to decrease the droplet size and droplet size distribution of the coarse emulsion. However, external flow (shear) causes internal streaming in the droplets, which increases the frequency of collision (and thus coalescence) of internal droplets with the outer water phase [4]. Besides, elongation of the droplets increases the interface available for release of internal droplets. Therefore, the release rate of internal droplets is dependent on the applied shear stress [5] and only moderate shear can be used for the production of double emulsions if a reasonable percentage of internal phase is required. This is the reason why double emulsions are in general polydisperse.

Florence and Whitehill [6] described four possible mechanisms for instability of W/O/W emulsions. These four mechanisms are (1) coalescence of the internal aqueous droplets; (2) coalescence of the oil drops; (3) rupture of the oil film separating the internal and external aqueous phases; (4) passage of water (and water-soluble material, e.g. a drug) to and from internal droplets through the oil layer. This last point is subdivided into two possible mechanisms: via reverse micellar transport and by diffusion across areas where the oil layer is very thin [3]. All these mechanisms are known to occur, both during preparation of double emulsions and during storage. They influence the size distributions of the internal and outer droplets, which are important characteristics for double emulsions and the stability thereof. Further, double emulsions are often characterized by the entrapment yield of a certain compound in the inner droplet fase and the stability in time.

An enormous amount of formulations for double emulsions is known in literature with various types of oil, different fractions of phases and different sorts of surfactants in varying concentrations (see Table 1). Combinations of surfactants in the outer water phase have a beneficial effect on stability and polymeric surfactants are very suitable emulsifiers (and stabilizers) for double emulsions, because they can protect double emulsions against coalescence by making them resistant to shear [3]. In general it can be stated that the formulation of double emulsions greatly influences the stability and droplet size, and this should be considered in conjunction with the choice of the preparation method.

Section snippets

General

The most important conventional emulsification devices are stirring apparatuses, rotor–stator systems and high-pressure homogenizers [2]. Stirrers are the earliest type of equipment that has been used for emulsification. The dispersed phase is broken up by the shear stresses of the turbulence. The energy consumption is usually large.

In rotor–stator systems, such as tooth-disc high-speed homogenizers and colloid mills, a high shear is generated between a rotor and a stationary smooth, roughened

Influence of surfactants

The type and concentration of surfactants affects the production process as well as the long-term stability of double emulsions. Emulsion formation in cross-flow and pre-mix membrane emulsifications is facilitated when the Laplace pressure is lowered by surfactants and the stability is improved because surfactants help to prevent coalescence. A surfactant with a low hydrophilic–lipophilic balance (HLB) is better soluble in oil and normally forms W/O emulsions, a surfactant with a high-HLB

Applications of double emulsions produced by membrane emulsification

The main application so far of double emulsions produced by membrane emulsification is as a drug delivery system [32]. For example, most anticancer drugs are used as emulsions because they are water-soluble. In the form of an emulsion it is possible to control release rates of medicine and suppress strong side effects of the drug. However, a single emulsion cannot be used since W/O emulsions generally have such a high viscosity that infusion of emulsions to arteries/capillaries via catheters is

Conclusions and outlook

Several papers show that it is possible to produce double W/O/W emulsions by means of membrane emulsification (as the second emulsification step). Especially the production of emulsions with SPG membranes showed promising results. In the medical field, this method even made it possible to develop a new drug delivery system for the treatment of liver cancer. No studies are known in which O/W/O emulsions were prepared by membrane emulsification.

However, there are also some drawbacks. It takes

Acknowledgement

This research was supported by the European Community, project QLRT-2000-01228.

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