Formation and stability of nano-emulsions

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Abstract

This review describes the principles of formation and stability of nano-emulsions. It starts with an introduction highlighting the main advantages of nano-emulsions over macroemulsions for personal care and cosmetic formulations. It also describes the main problems with lack of progress on nano-emulsions. The second section deals with the mechanism of emulsification and the dynamic light scattering technique for measurement of the droplet size of nano-emulsions. This is followed by a section on methods of emulsification and the role of surfactants. Three methods are described for nano-emulsion preparation, namely high energy emulsification (using homogenisers), low energy emulsification whereby water is added to an oil solution of the surfactant and the principle of the phase inversion temperature (PIT). A section is devoted to steric stabilisation and the role of the adsorbed layer thickness. The problem of Ostwald ripening (which is the main instability process of nano-emulsions) is described in some detail. The methods that can be applied to reduce Ostwald ripening are briefly described. This involves the addition of a second less soluble oil phase such as squalene and/or addition of a strongly adsorbed and water insoluble polymeric surfactant. The last part of the review gives some examples of nano-emulsions that are prepared by the PIT method as well as using high pressure homogeniser. A comparison of the two methods is given and the rate of Ostwald ripening is measured in both cases. The effect of changing the alkyl chain length and branching of the oil was investigated using decane, dodecane, tertadecane, hexadecane and isohexadecane. The branched oil isohexadcecane showed higher Ostwald ripening rate when compared with a linear chain oil with the same carbon number.

Introduction

Nano-emulsions are transparent or translucent systems mostly covering the size range 50–200 nm [1], [2]. Nano-emulsions were also referred to as mini-emulsions [3], [4]. Unlike microemulsions (which are also transparent or translucent and thermodynamically stable) nano-emulsions are only kinetically stable. However, the long-term physical stability of nano-emulsions (with no apparent flocculation or coalescence) make them unique and they are sometimes referred to as ‘Approaching Thermodynamic Stability’.

The inherently high colloid stability of nano-emulsions can be well understood from a consideration of their steric stabilisation (when using non-ionic surfactants and/or polymers) and how this is affected by the ratio of the adsorbed layer thickness to droplet radius as will be discussed below.

Unless adequately prepared (to control the droplet size distribution) and stabilised against Ostwald ripening (that occur when the oil has some finite solubility in the continuous medium), nano-emulsions may loose their transparency with time as a result of increase in droplet size.

The attraction of nano-emulsions for application in personal care and cosmetics as well as in health care is due to the following advantages:

(i) The very small droplet size causes a large reduction in the gravity force and the Brownian motion may be sufficient for overcoming gravity. This means that no creaming or sedimentation occurs on storage. (ii) The small droplet size also prevents any flocculation of the droplets. Weak flocculation is prevented and this enables the system to remain dispersed with no separation. (iii) The small droplets also prevent their coalescence, since these droplets are non-deformable and hence surface fluctuations are prevented. In addition, the significant surfactant film thickness (relative to droplet radius) prevents any thinning or disruption of the liquid film between the droplets. (iv) Nano-emulsions are suitable for efficient delivery of active ingredients through the skin. The large surface area of the emulsion system allows rapid penetration of actives. (v) Due to their small size, nano-emulsions can penetrate through the ‘rough’ skin surface and this enhances penetration of actives. (vi) The transparent nature of the system, their fluidity (at reasonable oil concentrations) as well as the absence of any thickeners may give them a pleasant aesthetic character and skin feel. (vii) Unlike microemulsions (which require a high surfactant concentration, usually in the region of 20% and higher), nano-emulsions can be prepared using reasonable surfactant concentration. For a 20% O/W nano-emulsion, a surfactant concentration in the region of 5–10% may be sufficient. (viii) The small size of the droplets allows them to deposit uniformly on substrates. Wetting, spreading and penetration may be also enhanced as a result of the low surface tension of the whole system and the low interfacial tension of the O/W droplets. (ix) Nano-emulsions can be applied for delivery of fragrants, which may be incorporated in many personal care products. This could also be applied in perfumes, which are desirable to be formulated alcohol free. (x) Nano-emulsions may be applied as a substitute for liposomes and vesicles (which are much less stable) and it is possible in some cases to build lamellar liquid crystalline phases around the nano-emulsion droplets.

Inspite of the above advantages, nano-emulsions have only attracted interest in recent years for the following reasons: (i) Preparation of nano-emulsions requires in many cases special application techniques, such as the use of high pressure homogenisers as well as ultrasonics. Such equipments (such as the Microfluidiser) became available only in recent years. (ii) There is a perception in the personal care and cosmetic industry that nano-emulsions are expensive to produce. Expensive equipments are required as well as the use of high concentrations of emulsifiers. (iii) Lack of understanding of the mechanism of production of submicron droplets and the role of surfactants and cosurfactants. (iv) Lack of demonstration of the benefits that can be obtained from using nano-emulsions when compared with the classical macroemulsion systems. (v) Lack of understanding of the interfacial chemistry that is involved in production of nano-emulsions. For example, few formulations chemists are aware of the use of the phase inversion temperature (PIT) Concept and how this can be usefully applied for the production of small emulsion droplets. (vi) Lack of knowledge on the mechanism of Ostwald ripening, which is perhaps the most serious instability problem with nano-emulsions. (vii) Lack of knowledge of the ingredients that may be incorporated to overcome Ostwald ripening. For example, addition of a second oil phase with very low solubility and/or incorporation of polymeric surfactants that strongly adsorb at the O/W interface (which are also insoluble in the aqueous medium). (viii) Fear of introduction of new systems without full evaluation of the cost and benefits.

Inspite of the above difficulties, several companies have introduced nano-emulsions in the market and within the next few years, the benefits will be evaluated. Nano-emulsions were used in the pharmaceutical field as drug delivery systems [7].

Acceptance of nano-emulsions as a new type of formulation depends on customer perception and acceptability. With the advent of new instruments for high pressure homogenizers and the competition between various manufacturers, the cost of production of nano-emulsions will decrease and that may approach that of classical macroemulsions.

Fundamental research in investigation of the role of surfactants in the process [5], [6] will lead to optimized emulsifier systems and more economic use of surfactants will emerge. The importance of phase behaviour in the preparation of nano-emulsions is also very crucial. As we will see later the method of mixing of oil, water and surfactant is very important.

In this review, I will discuss the following topics: (i) Fundamental principles of emulsification and the role of surfactants. (ii) Production of nano-emulsions using: high pressure homogenizers. The phase inversion temperature (PIT) principle. (iii) Theory of steric stabilization of emulsions. The role of the relative ratio of adsorbed layer thickness to the droplet radius. (iv) Theory of Ostwald ripening and methods of reduction of the process: incorporation of a second oil phase with very low solubility. Use of strongly adsorbed polymeric surfactants. (iv) Examples of recently prepared nano-emulsions and investigation of the above effects.

Section snippets

Mechanism of emulsification

To prepare an emulsions oil, water, surfactant and energy are needed. This can be considered from a consideration of the energy required to expand the interface, Δ (where ΔA is the increase in interfacial area when the bulk oil with area A1 produces a large number of droplets with area A2; A2A1, γ is the interfacial tension). Since γ is positive, the energy to expand the interface is large and positive. This energy term cannot be compensated by the small entropy of dispersion TΔS (which is

Methods of emulsification and the role of surfactants

With macroemulsions, several procedures may be applied for emulsion preparation, these range from simple pipe flow (low agitation energy L), static mixers and general stirrers (low to medium energy, LM), high speed mixers such as the Ultraturrex (M), colloid mills and high pressure homogenizers (high energy, H), ultrasound generators (MH). The method of preparation can be continuous (C) or batch-wise (B). With nano-emulsions, however, a higher power density is required and this restricts the

Preparation of nano-emulsions

Three methods may be applied for the preparation of nano-emulsions (covering the droplet radius size range 50–200 nm). Use of high pressure homogenisers (aided by appropriate choice of surfactants and cosurfactants), use of low energy emulsification method at constant temperature or application of the phase inversion temperature (PIT) concept.

Steric stabilization and the role of the adsorbed layer thickness

Since most nano-emulsions are prepared using non-ionic and/or polymeric surfactants, it is necessary to consider the interaction forces between droplets containing adsorbed layers (Steric stabilization). This was described in detail in several reviews and textbooks only a summary is given here [20], [21].

When two droplets each containing an adsorbed layer of thickness δ approach to a distance of separation h, whereby h becomes <2δ, repulsion occurs as a result of two main effects: (i)

Ostwald ripening

One of the main problems with nano-emulsions is Ostwald ripening which results from the difference in solubility between small and large droplets. The difference in chemical potential of dispersed phase droplets between different sized droplets as given by Lord Kelvin [22],cr=cexp2γVmrRTwhere c(r) is the solubility surrounding a particle of radius r, c(∞) is the bulk phase solubility and Vm is the molar volume of the dispersed phase.

The quantity (2γVm/rRT) is termed the characteristic length.

Practical examples of nano-emulsions

Several experiments were recently carried to investigate the methods of preparation of nano-emulsions and their stability [29], [29](a), [29](b), [29](c). The first method applied the PIT principle for preparation of nano-emulsions. Experiments were carried out using hexadecane and isohexadecane (Arlamol HD) as the oil phase and Brij 30 (C12EO4) as the non-ionic emulsifier. The phase diagrams of the ternary system water-C12EO4-hexadecane and water-C12EO4-isohexadecane are shown in Fig. 8, Fig. 9

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