Development of a percutaneous penetration predictive model by SR-FTIR

Area of Science:

• Analytical Chemistry
• Biophysics
• Toxicology

Background:

• Percutaneous penetration is crucial for drug delivery and risk assessment.
• Existing evaluation criteria like Log Pow and molecular weight have limitations.
• High spatial resolution Fourier transformed infrared (SR-FTIR) microspectroscopy offers potential for detailed molecular analysis.

Purpose of the Study:

• To develop a new evaluation criterion for percutaneous penetration.
• To complement existing parameters like Log Pow and molecular weight.
• To establish a predictive cartography of molecule distribution in skin.

Main Methods:

• Classic Franz cell experiments were conducted.
• Molecule distribution in skin was analyzed after 22 hours using High-Performance Liquid Chromatography (HPLC) as a reference and SR-FTIR.
• A multi-block data analysis technique (ComDim) was employed to determine the new S(index) criterion from SR-FTIR data.

Main Results:

• HPLC and SR-FTIR results were compared, showing good correlation.
• A novel predictive criterion, S(index), was established based on SR-FTIR data.
• A predictive cartography of molecule distribution in skin was generated and compared to OECD standards.

Conclusions:

• The new S(index) criterion and SR-FTIR-based cartography provide valuable insights for percutaneous penetration risk analysis.
• This approach can enhance the prediction of molecule distribution in skin.
• The findings support the development of new mathematical models for percutaneous penetration assessment.