Confocal Raman Spectroscopic Characterization of Dermatopharmacokinetics Ex Vivo.

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Dermatology

Background:

• Topical drug delivery requires understanding drug disposition in viable skin layers.
• Quantifying drug penetration and clearance below the stratum corneum is challenging.
• Confocal Raman spectroscopy offers potential for non-invasive in-depth skin analysis.

Purpose of the Study:

• To validate confocal Raman spectroscopy for quantifying drug uptake and clearance in the viable epidermis.
• To develop methods for correcting signal attenuation with skin depth.
• To establish metrics for topical drug bioavailability and bioequivalence.

Main Methods:

• Utilized skin cross-sections to identify keratin's amide I signal for depth-dependent signal correction.
• Employed 4-cyanophenol (CP) as a model penetrant to study uptake and clearance kinetics.
• Acquired confocal Raman data in a 'top-down' fashion, normalizing signals for depth analysis.

Main Results:

• Demonstrated that normalized Raman data can detect CP penetration up to 80 μm into the skin.
• Showcased the ability to distinguish drug disposition from different vehicles.
• Successfully detected the delivery of crisaborole into skin layers below the stratum corneum.

Conclusions:

• Confocal Raman spectroscopy is a viable tool for quantifying drug disposition in the viable epidermis.
• Normalized spectroscopic data provide metrics for topical bioavailability and bioequivalence.
• The developed methods enable sensitive detection of dermatological drug delivery.