Zinc Pyrithione: A Topical Antimicrobial With Complex Pharmaceutics

February 2016 | Volume 15 | Issue 2 | Original Article | 140 | Copyright © 2016

James R. Schwartz PhD

The Procter & Gamble Company, Cincinnati, OH


Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products. These particles slowly release molecularly active material to interact with the surface fungal and bacteria cells to control their population, functioning as slow-release reservoirs to provide extended and persistent benefits. This particulate nature, though, results in complex pharmaceutics to realize the full efficacy benefits; it is common to see products with the same ZPT level having widely varying levels of clinical performance. Several product matrix-determined factors directly impact resultant benefits: ZPT must be retained on the skin surface achieving uniform spatial distribution laterally as well as within hair follicles (especially on scalp); ZPT must be maintained as a physically stable dispersion in product; ZPT must be maintained in a chemically active form as there are many chemical reactions that can occur that can harm ZPT bioactivity. The benefits achievable by employing ZPT require significant pharmaceutics expertise to realize the full benefits of this active material.

J Drugs Dermatol. 2016;15(2):140-144.

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Zinc pyrithione (ZPT) is a widely used drug active to treat topical fungal conditions. It is also used cosmetically to exploit its breadth of antimicrobial activity. It has a history of safe and effective use for more than 50 years. Such a long history may obscure an appreciation of its development history, the breadth of beneficial activities realized over the years as well as the complex pharmaceutics discovered to be relevant in topical delivery of the material in its most active form. The intent of this review is to recount the history of this rationally developed drug, understand the unique physico-chemical properties that lead to the complex pharmaceutics and overview the range of activities and resultant benefits that can result from topical use on skin.

The History of Development of Zinc Pyrithione

The development of ZPT originated in a targeted discovery program at ER Squibb & Sons to model the natural antibiotic aspergillic acid (Figure 1A). Aspergillic acid was isolated in the 1940’s from Aspergillus strains as one of the materials responsible for the observed antimicrobial activity of the organism. A synthetic program was initiated to focus on the core chemical elements of a cyclic hydroxamic acid functional group in a pyrazine nucleus. The objective was to develop synthetic analogs with antifungal activity for agricultural applications.

As part of this synthetic program, sodium pyrithione was originally synthesized 1 and shown to exhibit significant antimicrobial activities. Both the sodium (Figure 1B) and zinc salt (Figure 1C) forms of this material were commercialized by the Mathieson-Olin Chemical Co. While the material never found use in the agricultural field, the zinc salt was discovered as very effective for controlling growth of the scalp fungus Malassezia (called Pityrosporum at the time) that causes dandruff.2

Physico-Chemical Properties of ZPT


ZPT is prepared industrially3 (Figure 2) from sodium pyrithione. The latter is synthesized by oxidation of 2-chloropyridine followed by mercaptization. The sodium salt is then precipitated with zinc sulfate, which after washing leads to the commercial material, which is normally utilized as an aqueous dispersion. The conditions of the precipitation can be manipulated to alter the morphology and size of the precipitating ZPT particle. ZPT can also be milled after precipitation to alter particle size. These factors contribute to the complex pharmaceutics of this material (see below).

Physical Properties of ZPT

ZPT is a white crystalline material in the dry state with a density of 1.8 g/cm.3 Solubility in water and most common solvents

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