Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation

Abstract

Nano-emulsions consist of fine oil-in-water dispersions, having droplets covering the size range of 100–600 nm. In the present work, nano-emulsions were prepared using the spontaneous emulsification mechanism which occurs when an organic phase and an aqueous phase are mixed. The organic phase is an homogeneous solution of oil, lipophilic surfactant and water–miscible solvent, the aqueous phase consists on hydrophilic surfactant and water. An experimental study of nano-emulsion process optimisation based on the required size distribution was performed in relation with the type of oil, surfactant and the water–miscible solvent. The results showed that the composition of the initial organic phase was of great importance for the spontaneous emulsification process, and so, for the physico-chemical properties of the obtained emulsions. First, oil viscosity and HLB surfactants were changed, α-tocopherol, the most viscous oil, gave the smallest droplets size (171 ± 2 nm), HLB required for the resulting oil-in-water emulsion was superior to 8. Second, the effect of water–solvent miscibility on the emulsification process was studied by decreasing acetone proportion in the organic phase. The solvent–acetone proportion leading to a fine nano-emulsion was fixed at 15/85% (v/v) with EtAc–acetone and 30/70% (v/v) with MEK–acetone mixture. To strength the choice of solvents, physical characteristics were compared, in particular, the auto-inflammation temperature and the flash point. This phase of emulsion optimisation represents an important step in the process of polymeric nanocapsules preparation using nanoprecipitation or interfacial polycondensation combined with spontaneous emulsification technique.

Introduction

Nano-emulsions are fine oil-in-water dispersions, having droplet covering the size range of 100–600 nm (Nakajima et al., 1993, Nakajima, 1997). Nano-emulsions are also referred to as mini-emulsions (Ugelstadt et al., 1973, El-Aasser et al., 1988). 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) makes them unique and they are sometimes referred to as “approaching thermodynamic stability” (Tadros et al., 2004, Girard et al., 1997.

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

• Unlike microemulsions (which require a high surfactant concentration, usually about 20% and higher), nano-emulsions can be prepared using lower surfactant concentration, a surfactant concentration comprised between 3–10% may be enough.

• The small size of the droplets for cutaneous use allows them to deposit uniformly on skin.

• Nano-emulsions are suitable for efficient delivery of active ingredients through the skin (Sonneville-Aubrun et al., 2004). The large surface area of the emulsion system, the low surface tension of the whole system and the low interfacial tension of the O/W droplets allow enhancing penetration of actives agents.

• Due to their small size, nano-emulsions can penetrate through the “rough” skin surface and this enhances penetration of actives.

• The fluidity nature of the system (at low oil concentrations) as well as the absence of any thickeners may give them a pleasant aesthetic character and skin feel.

• 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.

• 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.

• Nano-emulsions constitutes the primary step in nanocapsules and nanospheres synthesis using nanoprecipitation (Fessi et al., 1986, Fessi et al., 1989, Fessi et al., 1992) and the interfacial polycondensation combined with spontaneous emulsification (Bouchemal et al., 2004, Montasser et al., 2001). These two techniques require the spontaneous emulsification step in the same optimised conditions.

The droplets size and size distribution are depending on the spontaneity of emulsification (Gopal, 1968, Becher, 1983, Shahizdadeh et al., 1999). The spontaneity of the emulsification is poorly defined, since it should account not only for the rate of the emulsification process, but also for the volume and the particle size distribution of the produced emulsion. The spontaneity of the emulsification process depends mainly on the following variables: interfacial tension, interfacial and bulk viscosity, phase transition region and surfactant structure and concentration (Lopes-Montilla et al., 2002, Davies and Rideal, 1961, Aveyard et al., 1986, Aveyard et al., 1986, Miller, 1988, Miller and Raney, 1993, Miller, 1996, Hackett and Miller, 1988; Davies and Haydon, 1957).

Spontaneous emulsification is produced by different mechanisms which seem to be affected by the systems compositions and their physicochemical characteristics (Lopes-Montilla et al., 2002). In this paper, the influence of the physical properties of oils and of the surfactant nature on the emulsion size distribution was first studied. Once the oil and the surfactant optimised, the effect of water–solvent miscibility on the emulsification process was studied by changing acetone proportion in the organic phase.