P#61  Dandruff, part III : effective treatment requires products based on potent actives optimized for effective delivery to the scalp

James R. Schwartz, Thomas L. Dawson Jr., Joseph R. Kaczvinsky, Raphael Warren and Caroline W. Cardin. The Procter & Gamble Company, Cincinnati, OH

Dandruff is a fungal-mediated disease which responds well to topical delivery of anti-fungal materials. Anti-dandruff efficacy can be thought of as being determined by three factors: (1) intrinsic anti-fungal potency, (2) delivery of the anti-fungal to the scalp and (3) the presence of secondary mechanisms of action in addition to anti-fungal activity. Not all anti-dandruff actives are equally effective at controlling the disease nor are all formulated products based on a given technology equally effective at delivering the anti-fungal to the targeted area in a bio-available form. Finally, delivery of this technology in a cosmetically-acceptable product is also required to ensure patient compliance. One of the most potent anti-fungals available against the relevant fungus, Malassezia, is zinc pyrithione (ZPT). Zinc pyrithione is the coordination complex that has the empirical composition of two pyrithione moieties attached to a Zn2+ ion. The pyrithione moiety of ZPT was originally developed as a structural analog to a naturally-occurring anti-microbial (gibberellic acid). The zinc salt is particularly effective and its mechanism of action is believed to involve interference with the function of fungal ATPase. ZPT is accepted by the FDA in the US and regulatory bodies around the world as safe and effective for the treatment for dandruff and seborrheic dermatitis. Although ZPT has been utilized to treat dandruff for more than 40 years, not all ZPT materials used commercially are the same. ZPT is largely insoluble and is incorporated in products and delivered to the scalp as an insoluble particle. The size and shape of the particle control it's delivery, and concomitant efficacy, to the scalp. Since its introduction, we have optimized the particle morphology to balance the parameters of mass delivered to the scalp with bio-availability. The result is a particle of hexagonal morphology and an average diameter of 2.5 microns. By clinical evaluation, this is shown to be the optimum size and product formulations have been intricately designed specifically to deliver this particle. While ZPT is a potent anti-fungal, it also appears to confer secondary benefits relevant to the treatment of dandruff as well. For example, ZPT attenuates the irritation/inflammation process as indicated by cytokine release data. Also, while usage of ZPT-containing products clearly reduce the visible signs of dandruff (flaking), it also improves the sub-clinical signs relating to skin health. Net, when optimized for particle morphology and delivery in a cosmetically acceptable vehicle, ZPT remains an excellent therapeutic tool in the treatment of dandruff.