Nair Rajesh Sreedharan, Billa Nashiru, Morris Andrew P
School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, 43500, Semenyih, Selangor Darul Ehsan, Malaysia.
Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
AAPS PharmSciTech. 2025 May 29;26(5):147. doi: 10.1208/s12249-025-03143-2.
Drug delivery through the skin provides several advantages over other administration routes, including the avoidance of first-pass metabolism and gastrointestinal side effects, prolonged drug release, and significant improvement in patient compliance. It is imperative to study the in vitro behavior of drugs and formulations before proceeding to in vivo evaluations. As the ethical guidelines for scientific research evolve, there is an increasing emphasis on adopting alternative methods to reduce animal use. An in vitro permeation study (IVPT) estimates the rate and extent of drug permeation from a topical or transdermal delivery, determining its availability at the skin layers or into the systemic circulation. Vertical Franz diffusion cells are commonly employed for IVPT studies to evaluate the permeation of drugs across skin or other biorelevant membranes. This comprehensive review provides a clear understanding of the importance of optimizing in vitro experimental conditions to obtain reliable and reproducible data. We discuss various in vitro skin models, including excised human and animal skins, human skin equivalents (HSEs), synthetic membranes, and 3D-printed skin models. Additionally, a broad overview of setting up in vitro diffusion cells is provided. Emphasis is given on donor phase design, receptor medium selection, the importance of solubility and stability studies, sampling techniques, and analysis methods. Meticulous design and optimization of in vitro permeation experiments are crucial for generating reproducible data, which are essential for predicting the dermatokinetics of drugs and formulations.
与其他给药途径相比，经皮给药具有诸多优势，包括避免首过代谢和胃肠道副作用、延长药物释放以及显著提高患者依从性。在进行体内评估之前，研究药物和制剂的体外行为至关重要。随着科学研究伦理准则的不断发展，越来越强调采用替代方法以减少动物使用。体外渗透研究（IVPT）可估算局部或透皮给药中药物的渗透速率和程度，确定其在皮肤层或进入体循环的可用性。垂直式Franz扩散池通常用于IVPT研究，以评估药物透过皮肤或其他生物相关膜的渗透情况。这篇综述全面阐述了优化体外实验条件以获得可靠且可重复数据的重要性。我们讨论了各种体外皮肤模型，包括切除的人皮肤和动物皮肤、人皮肤等效物（HSE）、合成膜以及3D打印皮肤模型。此外，还对设置体外扩散池进行了概述。重点介绍了供体相设计、受体介质选择、溶解度和稳定性研究的重要性、采样技术以及分析方法。精心设计和优化体外渗透实验对于生成可重复的数据至关重要，而这些数据对于预测药物和制剂的皮肤动力学必不可少。
