Product Pharmacology and Medical Actives in Achieving Therapeutic Benefits

Abstract

Scalp skin is physiologically very similar to non-palmoplantar skin of the rest of the body, except for the very high concentration of sebaceous glands (Giacometti, 1965). The scalp environment, however, is much different in being covered by a thick fabric of hair. There are about 250 hair fibers per cm, which results, for a typical individual, in a hair surface area of 50,000 cm relative to the scalp surface area of 600 cm. Together, these parameters indicate the relative inaccessibility of the scalp surface to targeted delivery of actives; relatively low delivery efficiency in this protected environment is an inherent challenge to achieving therapeutic benefits. This is especially true of the most patientfriendly format—shampoos—since a rinsing step is involved and the product cannot interfere with achieving desired hair cosmetic benefits (compliance decreases dramatically if hair cosmetics are poor). This places a large demand on actives with high activity since delivery efficiency will be inherently low as well as development of product pharmacologies that maximize the benefit of the actives employed. This situation will be exemplified for the most common scalp care therapeutic products, those designed to treat dandruff and seborrheic dermatitis (D/SD) utilizing anti-fungal actives to reduce Malassezia content on the scalp. The most common anti-fungal materials used in D/SD scalp therapies include those based on rational chemical design principles (ketoconazole, climbazole, pyrithione zinc (PTZ), piroctone olamine and ciclopirox olamine) as well as materials originating from indeterminate histories (selenium sulfide, sulfur, coal tar, and salicylic acid). Because of the aforementioned demands on activity due to challenging delivery, only those materials with high intrinsic anti-fungal activity should be considered as the basis for therapeutic products. Based on measurement of minimal inhibitory concentrations (MIC) against Malassezia, the most potent materials from this group are pyrithione zinc, selenium sulfide, climbazole, and ketoconazole (VanGerven and Odds, 1995; Schmid and Ruhl-Horster, 1996). For a formulated therapeutic product to be effective, a potent active is a necessary but insufficient condition to achieve activity. The way the active is delivered to the scalp from the product formula, i.e., the product pharmacology, is at least as strong a determinant of in-use activity as the intrinsic active potency. For example, a comparison of clinical flake-reduction efficacy of a variety 1% PTZ-based D/ SD shampoo products demonstrates a wide range of magnitude of therapeutic benefits. Much of this variation is likely due to the varying efficiency of delivery of PTZ, a particulate active, to the scalp surface. Particulate PTZ delivery will be affected by the physical size and shape of the particle (as well as other formulation parameters, which will not be covered further here). Particles which are flat cover the scalp surface more efficiently than those that are not. The particle size is also critical as smaller particles provide better surface coverage but are more difficult to retain on the scalp after rinsing. These two opposing factors result in an optimum size to maximize active delivery. Shampoo product formulations utilizing PTZ particles optimized for delivery outperform those utilizing standard forms of the active (Fig 1). This exemplifies one variable, beyond active potency, that must be considered in selecting a therapeutic treatment. Another important pharmacological variable that must be considered is the role of the ‘‘non-functional’’ excipients in