Use of in vitro performance models in the assessment of drug delivery across the human nail for nail disorders

ABSTRACT

Introduction: Onychomycosis is the most prevalent nail condition, affecting between 5% and 20% of the population in western countries. Oral therapies are not the treatment of choice due to poor patient compliance, high relapse rates, severe side effects, and contraindication. However, the difficultly in curing the condition using topical delivery is partly due to both the nail structure presenting a complex barrier and the lack of understanding of how best to achieve delivery of drug to the nail bed.

Areas covered: Several novel in vitro models incorporating human nails discussed in this article have been developed in recent years that allow for the study of the mechanisms of ungual drug absorption and formulation efficacy to be assessed.

Expert opinion: The TurChub zone of inhibition model is a high-throughput performance screen for prototype formulations during development, while the robustness of the ChubTur nail permeation, TurSh nail penetration, and RoMar antifungal efficacy models ensure these can be validated for in vitro bioequivalence testing of generic products to reference listed drugs. With clinical trials being a costly and high-risk approach to generic approval, the described novel in vitro screening and performance testing techniques offer a de-risked and less-expensive route to market.

KEYWORDS:

• Bioequivalence
• nail
• onychomycosis
• performance
• topical
• validation

Article highlights

• Onychomycosis is a prevalent fungal nail disorder that is difficult to treat, partly due to patient compliance

• While topical treatment is a way of avoiding the side-effects and contraindications often observed with oral treatments, the human nail is a complex barrier to local drug delivery

• While the delivery of drugs across human skin has been subject to extensive researched, the understanding of drug delivery across the nail is comparatively less well understood

• Several novel in vitro models have been developed in recent years to assess the delivery (TurChub zone of inhibition, ChubTur nail permeation and TurSh nail penetration) and antifungal efficacy (RoMar) of drugs topically applied to full thickness human nails.

• The in vitro performance testing models can be employed to aid iterative formulation development of topical nail products and also for bioequivalence testing of generic products to reference listed drugs.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded