Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin.
BACKGROUND
Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT.


OBJECTIVES
To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[14C]PT was investigated.


METHOD
In vitro penetration of [14C]PT into and through excised human skin was measured following application of Zn[14C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum.


RESULTS
The steady-state flux and cumulative absorption of Zn[14C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[14C]PT and 3H2O absorption when dosed from both aqueous formulations, but not from castor oil.


CONCLUSION
These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [14C]PT kinetics, is controlled by particle dissolution and molecular speciation.
['Rush|Allison K|AK|', 'Nash|J F|JF|', 'Smith Iii|Edward D|ED|', 'Kasting|Gerald B|GB|']
D000279:Administration, Cutaneous D002266:Carboxymethylcellulose Sodium D002368:Castor Oil D016503:Drug Delivery Systems D006801:Humans D009942:Organometallic Compounds D011725:Pyridines D012629:Sebum D012869:Skin Absorption D012995:Solubility D013501:Surface-Active Agents
Percutaneous absorption Antimicrobial Dissolution In vitro skin penetration/permeation Topical bioavailability