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The Four Rs of Skin Delivery
By: Johann W. Wiechers, PhD, JW Solutions
Posted: December 9, 2008
page 4 of 6
The two ways of enhancing skin delivery are, however, fundamentally different. When the partition coefficient K (defined as the concentration at equilibrium of the penetrant in the stratum corneum divided by that in the formulation) is increased, a larger fraction of what is present in the formulation will end up in the stratum corneum at equilibrium. When the diffusion coefficient D is increased, the speed of transport through the stratum corneum will be enhanced. K therefore describes the ratio between two quantities at equilibrium whereas D describes the speed with which chemicals transverse through the stratum corneum. The question arises: Which of the skin delivery systems or parts thereof influence K and which affect D? The diffusivity is influenced by penetration enhancers, liposomes, transfersomes, ethosomes, niosomes, liquid crystals and emulsifiers within emulsions, because of their interaction with the skin lipid packing structure. Liposomes, volatile silicones, adjuvants and solubilizers like propylene glycol, dimethyl isosorbide and diethylene glycol monoethyl ether and emollients within emulsions affect the partition coefficient because they change the polarity of either the stratum corneum or the formulation or both.
Please note that this list is not complete. Occlusion, for instance, results in more water in the skin, which changes its polarity (the ingress of hydrophilic materials will be facilitated) but also affects the skin diffusivity because water has also been described as a skin penetration enhancer.10
When a cosmetic formulator is considering using a system, it is appropriate to identify whether the system affects the K or the D. First, consider whether the selected system is affecting the D because in order to obtain higher levels in the stratum corneum, the speed of transport through the stratum corneum should not be enhanced. Thereafter, consider the effect of the proposed system on K. If more active into the skin is better, then a system that increases K should be used. But for organic sun filters that need to stay on top of the skin rather than be within the stratum corneum, the use of K-enlarging skin delivery systems is not recommended. Table 1 summarizes this information and gives practical examples of which system to use for what type of application.
But the same question needs to be addressed as before: Is all this nanotechnology or not? Simply based on size, the liposomes, the transfersomes, the niosomes and the ethosomes clearly belong to nanotechnology, where it should be noted that the latter three are special types of liposomes, made from elastic membranes, non-ionic surfactants and prepared with high levels of ethanol, respectively. In short, this means that liposomes and the derivatives thereof are applications of nanotechnology and their effect on skin delivery will therefore be discussed in this series of articles.
Delivering for the Correct Period of Time
The last of the four Rs looks at nanotechnology as a skin delivery system to ensure the right chemical is being delivered to the right site at the right concentration for the corRect period of time. Assuming that the period of time during which an active is available at the site of action needs correction, this time can be either shortened or lengthened. Shortening is often very easy. Remove the formulation or the delivery device and skin delivery will cease.