Numerous physiological factors in healthy and diseased skin can affect topical drug delivery and consequently formulation design. For example, neonatal skin is more permeable than adult skin and site to site variations in permeability are well known with genital tissue more permeable than that on the head and neck with arm and leg skin even less permeable. However, it is with compromised skin, found in many conditions where topical dosage forms are applied, where solvent selection can be problematic.
Numerous disorders result in an eruption of the skin surface. Clearly in such cases, the barrier properties of the stratum corneum are compromised, allowing easier passage of drugs (and solvent) into and through the skin. Likewise, the erupted skin surface will allow increased water loss from the body. Psoriasis is a chronic recurring non-infectious scaling skin condition characterised by erythe-matous plaques covered with silvery scales. For topical therapy the loss of skin barrier integrity has been shown to be valuable for targeting drugs to the required site of action while minimising side effects (Anigbogu et al., 1996). Lichenoid eruptions are characterised by intensely itchy flat-topped papules while eczema is a further non-infectious eruptive condition, in which blistering occurs. Contact dermatitis can result from a direct irritant action of a substance on the skin (irritant contact dermatitis) or further exposure, following previous sensitisa-tion of the skin, from a contact allergen (allergic contact dermatitis). Irritant dermatitis is the more common of the two manifestations, and can be caused by many chemicals, solvents and detergents; sodium lauryl sulphate was used to induce irritant dermatitis before in vivo percutaneous absorption of several drugs was assessed (Wilhelm et al., 1991). Clearly having implications for therapy, hydrocortisone absorption was shown to increase nearly three-fold through the affected site, with a two-fold increase seen for indomethacin. Likewise, solvent permeation from an applied formulation will tend to increase where the barrier is compromised.
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