For designing effective topical drug therapy it is important to understand the principles of transmembrane transport and the unique structure of the stratum corneum. Some practical factors:
• Dosage-surface area relationships: In general, about 2 g of a topical product is required to cover the scalp, face, or hand; 3 g to cover an arm; 4 g to cover a leg; and 30 to 60 g to cover the entire body.
• Hydration of the stratum corneum: Hydration enhances the drug's solubility in and mobility through the skin (and its absorption) as much as tenfold. Hydration is usually achieved by using an occlusive vehicle or covering the treated skin with impermeable plastic film.
• Type of vehicle: In addition to their importance for hydration of the skin, vehicles vary in their partition coefficients (i.e., oil-water solubility ratio) for a given drug with respect to the stratum corneum. For example, a lipophilic drug moves more readily into the epidermis if it is in an aqueous vehicle, to which it is less tightly bound. Also, certain vehicles are soothing in various types of skin eruptions; dry, chronic inflammation often improves with drugs administered in lipophilic vehicles, whereas moist acute inflammation is best treated with aqueous preparations. Chemical constituents of vehicles can occasionally cause irritation or allergic sensitization that in turn may enhance penetration of drugs. Remember that for most topical drugs the vehicle constitutes more than 99% of the formulation.
• Variation in penetration at different anatomic sites: Drug penetration is inversely related to thickness of the stratum corneum. Thus, permeability (and often toxicity) is greater in areas of thinner skin, such as the face or scrotum.
• Inflammation: Permeability to most drugs is greater in inflamed skin.
• Age: Systemic toxicity from topically applied drugs is most likely in infants and small children because of their high ratio of surface area to body weight
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