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. 2017 Oct;18(7):2702-2705.
doi: 10.1208/s12249-017-0752-y. Epub 2017 Mar 13.

Trans-ungual Delivery of AR-12, a Novel Antifungal Drug

Avadhesh Singh Kushwaha  1 , P Sharma  1 , H N Shivakumar  2 , C Rappleye  3 , A Zukiwski  4 , S Proniuk  4 , S Narasimha Murthy  5
Affiliations

Trans-ungual Delivery of AR-12, a Novel Antifungal Drug

Avadhesh Singh Kushwaha et al. AAPS PharmSciTech. 2017 Oct.

Abstract

AR-12 is a novel small molecule with broad spectrum antifungal activity. Recently, AR-12 was found to be highly active against Trichophyton rubrum, one of the predominantly responsible organisms that cause onychomycosis. The primary objective of this project was to investigate the ability of AR-12 to penetrate into and across the human nail plate followed by improving its trans-ungual permeation using different penetration enhancers. TranScreen-N™, a high throughput screening method was utilized to explore the potential nail penetration enhancers to facilitate the drug delivery through the nail. This screen demonstrated that dexpanthenol and PEG 400 were the most efficient enhancers. The in vitro permeation studies were performed across the human cadaver nail plates for 7 days with three AR-12 (5% w/v) formulations containing 10% w/v dexpanthenol (Formulation A), 10% w/v PEG 400 (Formulation B), and a combination of 10% w/v dexpanthenol + 10% w/v PEG 400 (Formulation C). The in vitro studies concluded that dexpanthenol and PEG 400 were able to deliver a significant amount of AR-12 into and across the nail plate that was found to be more than MIC 50 level of the drug.

Keywords: AR-12; TranScreen-N™; Trichophyton rubrum; onychomycosis; ungual and trans-ungual drug delivery.

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