A computational workflow for end-to-end simulation of percutaneous absorption.

Area of Science:

• Computational toxicology
• Pharmacokinetics
• Dermal absorption modeling

Background:

• In silico modeling offers a powerful alternative to traditional in vitro and in vivo methods for assessing dermal absorption.
• Developing user-friendly tools is crucial for broader adoption by non-specialists in regulatory and research settings.

Purpose of the Study:

• To develop an automated, end-to-end workflow for in silico modeling of percutaneous absorption.
• To create a digital twin for simulating transdermal permeation accessible to non-modeling experts.

Main Methods:

• A KNIME-based workflow integrating physicochemical property informatics, molecular dynamics, and QSPRs.
• Physiologically based pharmacokinetic (PBPK) modeling incorporating permeant/solvent evaporation for unoccluded conditions.
• Automated data processing, result reporting, and formulation database management.

Main Results:

• The workflow successfully predicted percutaneous absorption, aligning well with published in vitro permeation test (IVPT) data.
• Model predictions accurately reflected the influence of formulation vehicles and evaporation on absorption.

Conclusions:

• The automated workflow simplifies complex in silico dermal absorption simulations for non-experts.
• The model robustly handles various formulation and exposure conditions, including volatile compound evaporation.