Print this Page

How Different Types of Emulsifiers can Influence Dermal and Transdermal Delivery of Active Ingredients from Emulsions – Dr Anja Otto, North-West University, South Africa

Session 4 – 11 September 2013
Anja explained that emulsions are unstable and need to be stabilized by emulsifiers. Three different emulsifiers were chosen to stabilise emulsions. Their properties, droplets sizes, viscosity and stability were examined. The skin absorption was discussed and how the different charges affected skin absorption.

Emulsions are thermodynamically unstable systems that necessitate emulsifiers for the formation and stabilisation of them. A literature review has shown that emulsifiers could affect dermal and transdermal delivery, depending on the structure and physicochemical properties of the emulsifier/emulsifier system, such as the hydrophilic chain length, hydrophilic-lipophilic balance (HLB) value, surfactant association structure, emulsifier charge or solid particles vs. surfactant.

In this study, three different biopolymers with different charges, i.e. whey proteins alone and in combination with chitosan or carrageenan, were chosen as emulsifiers. In previous studies it was shown that whey proteins can be used to stabilise emulsions and the stability could be improved by the electrostatic deposition of oppositely charged polysaccharides (e.g. carrageenan) onto the whey proteins.

Primary o/w emulsions at different pH values (pH 4, 5 and 6) were prepared by ultrasonication using only whey proteins as emulsifiers. The oil phase consisted of 2% salicylic acid dissolved in caprylic/capric triglyceride. The water phase was a citrate-phosphate buffer containing the hydrated whey proteins. The primary emulsions were then diluted with citrate-phosphate buffer at the specific pH values containing carrageenan, chitosan or no additional biopolymer. The different pH values (pH 4, 5 and 6) for the emulsions were chosen owing to the expected charge of the whey proteins, carrageenan and chitosan. At pH 5, the net electrical charge of the whey proteins is expected to be close to zero, because the isoelectric point is approximately 5.2. The whey proteins are supposedly positively charged at lower pH values (e.g. pH 4) and negatively charged at higher pH values (e.g. pH 6). Chitosan is a cationic biopolymer and is expected to be positively charged below pH 6.5. Carrageenan, in contrast, is an anionic biopolymer and is expected to be negatively charged at pH values above 2.

The various emulsions were investigated for their emulsion properties, e.g. droplet size, zeta potential, viscosity and stability (creaming index). Furthermore, release studies were carried out using Franz type diffusion cells and nitrocellulose as the membrane to separate the donor from the receptor phase. The formulations were then applied onto split-thickness human abdominal skin in vitro using Franz type diffusion cells and the dermal and transdermal delivery of salicylic acid was determined.

Zeta potential analysis of the final emulsions indicated that the polysaccharides carrageenan and chitosan were adsorbed to the whey proteins at the interface. Decreased zeta potential values were obtained with the emulsions containing whey proteins and carrageenan compared to the emulsions comprising only the whey proteins as emulsifiers. This was due to the adsorption of anionic carrageenan to the whey proteins at the interface. Similarly, the emulsions containing whey proteins and chitosan showed an increase in the zeta potential values because of the adsorption of the cationic chitosan to the whey proteins.

Creaming stability measurements and droplet size determination over a time period of 7 days revealed that not all emulsions were stable towards creaming (increase in creaming index) and flocculation and/or coalescence (increase in mean droplet size over time). Therefore, skin absorption studies were only conducted with the most stable emulsions, including the whey protein emulsions at pH 4, 5 and 6, in order to investigate the influence of the emulsion pH on skin delivery, and the three different emulsions at pH 6 (solely whey, whey + carrageenan and whey + chitosan) in order to assess the influence of the different biopolymer layers at the interface on skin delivery of salicylic acid.

The release study showed only small differences in the release of salicylic acid from the various tested emulsions. The release of salicylic acid from the whey protein emulsion at pH 4 was lower than from the same emulsions at pH 5 and 6, which was the opposite trend to the skin absorption data, as mentioned later. Furthermore, neither the addition of chitosan nor carrageenan to the whey protein emulsion at pH 6 significantly altered the release rate of salicylic acid.

The skin absorption study revealed a decreasing dermal and transdermal delivery of salicylic acid with increasing pH, which could be explained by adecreasing availability of the unionized species with increasing pH, which is considered to be the preferred form permeating the skin. However, the increase in transdermal delivery for the whey protein emulsion at pH 4 was much higher than what could be expected solely from the effect of the degree of ionisation. This formulation was the only emulsion with a positive zeta potential value and it was hypothesised that in addition, the positively charged emulsion droplets at pH 4could have interacted with the negatively charged skin surface, yielding improved skin absorption. The comparison of the skin absorption data of the three emulsions at pH 6 revealed that the adsorption of chitosan to the whey proteins at the interface enhanced the transdermal delivery of salicylic acid. However, the addition of carrageenan to the whey protein emulsion did not affect the dermal and transdermal delivery. The enhanced transdermal delivery due to the addition of chitosan could be explained by the positively charged chitosan. Though the zeta potential of this emulsion was slightly negative, there will still have been a considerable number of positively charged amino groups on the chitosan surface, which could interact with the negatively charged skin surface. The other two emulsions (solely whey, whey + carrageenan) at pH 6 had significantly lower zeta potential values with a lower tendency to interact with the skin surface.

In summary, this study showed that the emulsifiers and their different charges significantly affected skin absorption and the influence was more pronounced than the release of salicylic acid from the various formulations.

Permanent link to this article: