Zhang Duo, Deacon Benjamin N, Li Weijun, Lian Guoping, Chen Tao
School of Chemistry and Chemical Engineering, University of Surrey, Guildford GU2 7XH, UK.
School of Chemistry and Chemical Engineering, University of Surrey, Guildford GU2 7XH, UK; Unilever R&D Colworth, Unilever, Sharnbrook MK44 1LQ, UK.
Int J Pharm. 2025 Feb 10;670:125084. doi: 10.1016/j.ijpharm.2024.125084. Epub 2024 Dec 15.
Presented is the development of a workflow for end-to-end (e2e) in silico modelling of percutaneous absorption under a range of test conditions, integrating multiple calculation and analysis steps for in-silico simulation of dermal absorption. The aim is to achieve a digital twin that can be used by non-modelling experts to simulate transdermal permeation.
A KNIME-based toolbox is used to create the workflow for the E2E in-silico model. The workflow first combines physicochemical property informatics (ChemAxon), molecular dynamics (MD) modelling, and quantitative structure-property relations (QSPRs) to calculate the diffusion and partition properties of permeants in heterogeneous skin layers and complex formulation vehicles. These are then set as input parameters to physiologically based pharmacokinetics (PBPK) model to simulate percutaneous absorption under complex in vitro testing or in vivo exposure conditions set by the end user. Integrated into the PBPK model is the evaporation of volatile permeants and solvents for in vitro unoccluded conditions. The workflow generates a report of the results and records the tested formulation in a database.
The workflow has been tested against several sets of published in vitro permeation test (IVPT) results of percutaneous absorption involving different formulation vehicles. The model predictions of formulation and evaporation effects on percutaneous absorption agreed well with experimental data.
By automating multiple calculation steps from permeant property, diffusion-partition skin layers and formulation vehicles, to PBPK modelling of dermal absorption, the workflow provides a user-friendly means for non-modelling experts to conduct in-silico simulations of transdermal absorption under various conditions. The workflow is robust to simulate the impact of complex formulation and exposure conditions including evaporation of volatile permeants and solvents on the delivery into the skin.
介绍一种工作流程的开发，该流程用于在一系列测试条件下对经皮吸收进行端到端（e2e）的计算机模拟建模，集成了多个计算和分析步骤以进行皮肤吸收的计算机模拟。目的是实现一个数字孪生模型，可供非建模专家用于模拟透皮渗透。
使用基于KNIME的工具箱来创建用于端到端计算机模型的工作流程。该工作流程首先结合物理化学性质信息学（ChemAxon）、分子动力学（MD）建模和定量结构-性质关系（QSPRs），以计算渗透物在异质皮肤层和复杂制剂载体中的扩散和分配特性。然后将这些设置为基于生理的药代动力学（PBPK）模型的输入参数，以模拟最终用户设定的复杂体外测试或体内暴露条件下的经皮吸收。对于体外未封闭条件，挥发性渗透物和溶剂的蒸发被集成到PBPK模型中。该工作流程生成结果报告并将测试的制剂记录在数据库中。
该工作流程已根据几组已发表的涉及不同制剂载体的经皮吸收体外渗透试验（IVPT）结果进行了测试。该模型对制剂和蒸发对经皮吸收影响的预测与实验数据吻合良好。
通过自动化从渗透物性质、扩散-分配皮肤层和制剂载体到皮肤吸收的PBPK建模的多个计算步骤，该工作流程为非建模专家提供了一种用户友好的方法，用于在各种条件下进行经皮吸收的计算机模拟。该工作流程能够可靠地模拟复杂制剂和暴露条件的影响，包括挥发性渗透物和溶剂的蒸发对皮肤给药的影响。
