Topical formulations are the most common therapeutic agents in the treatment of skin diseases. They contain one or more active pharmaceutical ingredients (API) which need to penetrate or permeate the skin in order to exert their effect. However, after application a part of the formulation is removed from the skin due to contact with the environment. Therefore, a part of the active is then not available for penetration and thus, a loss in therapeutic effect will result. To achieve the desired therapeutic outcome a sufficient fraction of the formulation must remain on the skin. The extent to which the loss of preparation affects penetration and permeation is less investigated. This work presents a method to examine the influence of mechanical stress and formulation loss on skin permeation. A movable punch with a defined weight simulated contact between clothing or skin and the applied formulation. Weight of the tool, number of contacts and speed settings were variable and were investigated. Ex vivo permeation experiments were performed in Franz diffusion cells using porcine skin. Three preparations with nonivamide as active ingredient were chosen as model formulations: A semisolid cream, an oil-in-oil emulsion and a film-forming formulation. The last two show sustained permeation profiles. The method uses skin-to-formulation and clothing-to-formulation contact to simulate the removal of the formulations from the skin.
Keywords: Dermal drug delivery; Nonivamide; Skin permeation; Substantivity.
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