Revisiting techniques to evaluate drug permeation through skin

ABSTRACT

Introduction

Investigating the transportation of a drug molecule through various layers of skin and determining the amount of drug retention in skin layers is of prime importance in transdermal and topical drug delivery. The information regarding drug permeation and retention in skin layers aids in optimizing a formulation and provides insight into the therapeutic efficacy of a formulation.

Areas covered

This perspective covers various methods that have been explored to estimate drug/therapeutics in skin layers using in vitro, ex vivo, and in vivo conditions. In vitro methods such as diffusion techniques, ex vivo methods such as isolated perfused skin models and in vivo techniques including dermato-pharmacokinetics employing tape stripping, and microdialysis are discussed. Application of all techniques at various stages of formulation development where various local and systemic effects need to be considered.

Expert opinion

The void in the existing methodologies necessitates improvement in the field of dermatologic research. Standardization of protocols, experimental setups, regulatory guidelines, and further research provides information to select an alternative for human skin to perform skin permeation experiments to increase the reliability of data generated through the available techniques. There is a need to utilize multiple techniques for appropriate dermato-pharmacokinetics evaluation and formulation’s efficacy.

KEYWORDS:

• Skin
• dermato-pharmacokinetics
• human skin alternatives
• microdialysis
• permeation study
• topical delivery
• tape stripping

Article highlights

• Topical and transdermal delivery has become attractive strategy for delivery of therapeutics.

• Various in vitro, ex vivo, and in vivo methods are explored for determination of drug permeation through skin and retention in skin layers.

• New synthetic membranes are being explored to mimic the in vivo skin, though these membranes lack skin lipid alignment.

• The 3D in vitro skin surrogates are utilized as alternatives for animal and human skin.

• In vivo studies like microdialysis and skin biopsy are explored to determine skin permeation and retention.

• Various techniques like tape stripping, ATR-FTIR spectroscopy and Confocal Raman Spectroscopy are used adjunct to the ex vivo and in vivo methods to determine skin retention

• 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.