Principles of Topical Treatment: Advancement in Gel Vehicle Technology

A key characteristic of skin disease is that it is easily accessible, facilitating both diagnosis and treatment. In inflammatory skin disease, the inflammation is, even when deep, only a few millimeters from the surface. Cutaneous infectious organisms, such as superficial fungi, may be only microns from the skin surface. Thus, topical treatment, applying medications directly to the site where there are needed, is feasible. Topical treatment offers the advantage of being able to use high concentrations of potent agents locally, with low risk of systemic effects

This does not mean that achieving successful topical treatment is simple or easy.^1,2 (Table 1) While the targets of topical treatment may lie close to the surface, the skin surface barrier presents a considerable hurdle to reaching the target. The skin surface is designed to be a barrier to percutaneous absorption, and this barrier can be formidable (depending on location³). Moreover, complex physical chemistry determines the absorption of topically applied medications. The physical chemistry can result in unexpected results. For example, doubling the concentration of an active ingredient does not necessarily increase—much less double—the delivery of that active ingredient. Finally, getting patients to apply the medicine is not automatic. We should not think of the application of medication as automatic just because we prescribed the product. Using medication is a complex behavior that entails considerable effort on patients' part; it is a far more complicated behavior than just taking a pill, and patients don’t take pills very well, either.

The purpose of this manuscript is to provide an overview of topical therapy, important characteristics of topical formulations, and how these issues apply to a new topical gel delivery system. We will consider the structure and barrier characteristics of the skin, the physical chemistry of delivery of applied drug, and issues related to getting patients to apply drug. These topical treatment issues have important implications for clinical practice.

Skin is composed of multiple layers, beginning with stratum corneum on the surface, viable epidermis beneath it, followed by papillary and reticular dermis. Superficial fungal infections are limited to the stratum corneum. Common inflammatory diseases such as atopic dermatitis and psoriasis are limited to the epidermis and papillary dermis, while cutaneous lupus and bug bite reactions are deeper, involving reticular dermis.

The major barrier to percutaneous absorption lies within the stratum corneum. Barrier function depends on the critical role of lipids, including ceramides, cholesterol, and free fatty acids.^3,4 This multilamellar lipid barrier helps to maintain homeostasis by preventing evaporation of water from the body and by blocking entry of external exposures. This barrier presents a hurdle to delivery of hydrophilic, polar drugs through the skin.

The physical chemistry of the delivery of applied drugs is complex.⁶ When a topical product is applied to the surface of the skin, there are two phases in contact: the drug vehicle phase and the skin phase. This is similar to the two phases that sit separately in an oil & vinegar salad dressing. For active drug molecules to enter the skin, the drug must partition from the vehicle into the skin. Drugs that stay partitioned in the vehicle cannot be effective.