Methods for in vitro percutaneous absorption studies III: hydrophobic compounds.

Area of Science:

• Dermal absorption studies
• Pharmacokinetics
• Cosmetic science

Background:

• In vitro methods are crucial for predicting skin absorption of cosmetic ingredients.
• Hydrophobic compounds often exhibit poor permeation in standard in vitro models.
• Understanding factors influencing in vitro-in vivo correlation is vital for safety and efficacy assessments.

Purpose of the Study:

• To investigate the in vivo and in vitro skin absorption of two hydrophobic fragrance ingredients.
• To evaluate the impact of different receptor fluids on in vitro permeation.
• To assess the skin barrier integrity during in vitro absorption studies.

Main Methods:

• In vivo and in vitro permeation studies using rat skin.
• Formulation of hydrophobic compounds in petrolatum and acetone vehicles.
• Testing various receptor fluids including saline, serum, organic solvents, and nonionic surfactants.
• Assessment of skin barrier integrity using control compounds (cortisone, urea, water).

Main Results:

• In vivo permeation was significantly higher (8-fold for compound I, 95-fold for compound II) than in vitro.
• Replacing saline with a 6% polyethylene glycol 20 oleyl ether solution improved in vitro absorption, achieving 61-73% of in vivo levels for compound I.
• Compound II showed lower in vitro recovery (32% of in vivo) even with the optimized receptor fluid.
• Skin integrity was maintained with the chosen surfactant solution.

Conclusions:

• Optimized in vitro receptor fluids can partially bridge the gap between in vivo and in vitro skin absorption for hydrophobic compounds.
• Significant discrepancies between in vivo and in vitro results may persist, particularly for highly hydrophobic substances.
• Further refinement of in vitro models is necessary for accurate prediction of dermal absorption for fragrance ingredients.