3.6.1.1.1.1 The diffusion barrier
Human skin is best and most relevant type of skin (Sekkat and Guy 2001). Isolated SC sheets, epidermis and full thickness skin may be used. Although the latter two forms have the advantage of greater mechanical stability, high enzymatic metabolic activity in those viable skin layers is a disadvantage (Bronaugh and Maibach 1991; Tauber 1989) since the concentration of the diffused substance in the receptor compartment may be underestimated.
Since excised human skin for diffusion studies is obtained from autopsies or plastic surgery, a problem in its availability is encountered. Alternative models are animal skin and artificial membranes (Haigh and Smith 1994).
Animal skin is considered an alternative although the penetration enhancements are generally greater than those obtained with human skin (Williams and Barry 2012). Pig skin is considered the most relevant model for human skin (Bhatia and Singh 1996; Gray and Yardley 1975; Klain et al., 1986; Meyer et al., 1978), in addition to mouse, rat and guinea pig skin which show higher permeation rates (Dick and Scott 1992; Pendlington et al., 1998; Roberts and Mueller 1990; Sato et al., 1991). Also rabbit (Katz and Touitou 1991) and monkey
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Artificial membranes are models of lower variability. The simple structure lipid membranes or the more complex structure ones (e.g. liposomes consisting of SC lipids fixed to a supporting filter (Matsuzaki et al., 1993)) have the disadvantage of absence of pores. Another recent option is artificial membranes consisting of silicone and poly (2-hydroxyethyl methacrylate) which allow drug penetration through the lipid and the pore route (Hatanaka et al., 1990; Hatanaka et al.,