Evaluation of skin absorption of drugs from topical and transdermal formulations

ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

摘要：皮肤屏障功能主要由角质层（stratum corneum）介导，是药物经皮给药临床实践中的一大核心挑战。尽管如此，随着局部外用与经皮给药制剂研发技术的进步，已有大量生物活性化合物可通过经皮给药途径实现成功给药。对这类新型药物递送系统开展体外（in vitro）与体内（in vivo）评价，是表征其质量与药效的必要手段。本综述梳理了用于评估药物经皮吸收的主流方法，可为药物制剂研发人员设计药物递送系统提供辅助工具。本文讨论的体外方法包括采用Franz扩散池（Franz-type diffusion cells）的皮肤渗透实验、用于研究药物经皮渗透的皮肤滞留实验与胶带剥离法；体内方法则包括动物模型的临床前药代动力学研究。此外，本综述还涵盖了皮肤微透析的替代研究方法。本文还综述了利用共聚焦激光扫描显微镜（confocal laser scanning microscopy）、拉曼共聚焦显微镜（Raman confocal microscopy）以及衰减全反射傅里叶变换红外光谱（attenuated total reflectance Fourier-transform infrared spectroscopy）开展的药物经皮吸收及吸收促进剂作用机制相关研究的最新进展。