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Introduction

The skin consist of layers called the epidermis and certain appendages such as sweat glands, sebaceous glands (which secrete an oily substance), hair, and nails. There also exists a subcutaneous layer beneath the dermis. The outermost layer of the epidermis is termed the stratum corneum. It consist principally of dead epithelial cells that are filled with a protein, keratin, which waterproofs and toughens the skin. Underlying the stratum corneum are layers comprising granular spinous cells, keratinocytes, melanocytes, and Langhan¢ s cells. The dermis, which is below the epidermis, comprises connective tissue and a number of different cell types, it maintains and nourishes the epidermis through its network of capillaries and lymphatic vessels, sweat glands and hair follicles, which originate in the dermis and penetrate the stratum corneum of the epidermis, a potential route of penetration by drugs or chemicals. The subcutaneous layer is the innermost layer and is composed of loose connective tissue and many fat cells. It provides some degree of insulation and is a location for food storage and the site for subcutaneous injection.

Few chemicals or drugs are absorbed rapidly from intact skin. In fact, the skin effectively retards the diffusion and evaporation even of water except through the sweat glands. There are, however, a few notable exceptions (e.g., certain types of nerve gases, as well as insecticides, scopolamine, and nitroglycerin), and instances where a penetration enhancer (e.g., dimethyl sulfoxide) serves as a vehicle for the drug.

Several factors affect the transport of drugs through the skin (percutaneous) once they are applied topically. The absorption of drugs through the skin is enhanced if the drug is highly soluble in the fats (lipids) of the subcutaneous layer. The addition of water (hydration) to the stratum corneum greatly enhances the percutaneous transport of corticosteroids (anti-inflammatory steroids) and certain other topically applied agents. Hydration can be effected by wrapping the appropriate part of the body with plastic film, thereby facilitating dermal absorption. If the epithelial layer has been removed (denuded) by abrasion or burns, or if it has been affected by a disease, penetration of the drug may proceed more rapidly. A drug will be distributed (partitioned) between the solvent and the lipids of the skin according to the solubility of the solvent in water or lipids. Topical absorption of drugs is facilitated when they are dissolved in solvents that are soluble in both water and lipids. Highly water-soluble polar molecules, which have a lesser tendency to solubility in lipids, essentially cannot be absorbed percutaneously. Thus, a drug penetrates the skin at a rate determined primarily by its tendency to dissolve in water, or lipids, or both.