(439e) Development and Production of Oil-in-Water Vehicles Microemulsion for Dermal Application of Ectoin

Over the last years the development of skin penetration enhancers, mainly on the basis of microemulsions have attracted interest for their ability to increase absorption and permeability of drug compounds to and through the skin. Microemulsions are type of emulsion with uniform small droplet size. They are defined as a system of water, oil and surfactants, usually in conjunction with a co-surfactant, and are thermodynamic stable liquids (1). This type of oil-water dispersions are also referred to as submicron emulsion and miniemulsions. Their main advantages are easy preparation, long-term stability and the ability for incorporating large dose of drug with different lipohilicty.

Ectoin (1,4,5,6-tetrahydro-2-methyl-4-pyrimidecarboxylic acid), is one of the most common compatible solutes found in halophilic bacteria, and in recet studies was found to be non toxic and to stabilize and protect cells and biopolymers of the skin against stress (2).

In this work, the aim was to develop a formulation based on an oil-in-water (O/W) microemulsion that contained the molecule Ectoin, with suggest for its topical administration to treat neurodermitic skin. Moreover, composing an O/W-vehicle from non-irritating pharmaceutically acceptable ingredients (oils and surfactant), may create a formulation which hold fewer side-effects than the systemic therapies in current use.

O/W formulations containing 5% Ectoin were prapared from diffenet oils on a basic of the surfactants: glyceryle stearate, ceteth-20 and stearyl alcohol; and the addition of different permeation enhancers (Decyle Oleate, Oleic Acid, Span 85, Propylene glycole, cholesterol) to the formulation was examined for their influece on increasing the Ectoin dermal absopsion.

The ability of the formulation to apply the molecule Ectoin into the skin was examined by permeation studies on porcine ear skin, with the use of Franz diffusion cells system and the Ectoin concentration was analysed by HPLC.

The permeation experiments revealed that the addition of Decyle Oleate or Oleic Acid to the formulation, resulted in a 3-time enhancing the Ectoin dermal absopsion. In addition, comparing the Ectoin dermal absopsion from the O/w formulation to that from other known pharmaceutical creams containing Ectoin, showed that the O/W formulation was able to apply much more ectoin (0,22mg/cm²) into the skin in comparison to the other creams that were applying only 0,01-0,02mg/cm² Ectoin in to the skin.

For preparing the o/w emulsion, membrane emulsification method was examined with the use of tubular Al2O3 ceramic membranes which hold different characteristic of surface area, pore size, and numbar of channels, in order to achieve a small droplet size with a narrow size distribution.

In comparison to the conventional emulsification methods, the membrane emulsification may provided more control of the drop size and size distribution, which is influenced by membrane pore size, agitation speed, continuous phase viscosity, interfacial tension between the phases, as well as the chemistry of the system - such as surfactant type and properties (3). In experiments with different ceramic membranes a drop size of 300nm was finally achieved with the narrowest size distribution. These results were compared to experimental data of standard emulsification methods such as rotor- and a high-pressure homogenizing.

References:

(1) Kreilgaard, M. Influence of microemulsions on cutaneous drag delivery. Advanced Drug Deliver Reviews, 54 Suppl.1:s77-s98 (2002).

(2) Bünger J., Degwert J., Driller H. The protective function of compatible solute ectoin on the skin, skin cells and its biomolecules with respect to UV radiation, immunosuppression and membrane damage. IFSCC Mag., 4:127-131 (2001).

(3) Charcosset C., Limayem I., Fessi H. The membrane emulsification process-a review. Journal of chemical technology and biotechnology, 79:209-218 (2004).