In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation

Area of Science:

• Pharmacokinetics
• Dermal Drug Delivery
• Analytical Chemistry

Background:

• In vitro models are crucial for understanding drug permeation across human skin.
• Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is a hydrophobic molecule with potential therapeutic applications requiring efficient delivery.
• Optimizing experimental conditions is essential for accurate measurement of drug diffusion.

Purpose of the Study:

• To optimize in vitro experimental conditions for measuring Delta(9)-tetrahydrocannabinol (Delta(9)-THC) permeation across human skin.
• To compare Delta(9)-THC permeation rates through intact and stratum corneum (SC) stripped skin.
• To evaluate the efficacy of various receiver solutions for Delta(9)-THC diffusion studies.

Main Methods:

• Utilized a flow-through diffusion cell system for in vitro human skin permeation studies.
• Compared Delta(9)-THC permeation using intact and SC-stripped skin models.
• Evaluated receiver fluids including HEPES-buffered Hank's balanced salt solution (HHBSS) with bovine serum albumin (BSA), Polyoxyethylene 20 Oleyl Ether (Brij 98), and hydroxypropyl-beta-cyclodextrin (HPBCD).

Main Results:

• Delta(9)-THC permeability was significantly higher in Brij 98 solutions compared to 4% BSA.
• Higher BSA concentration (6%) demonstrated significantly greater Delta(9)-THC permeation than 4% BSA.
• HPBCD proved unsuitable as a receiver solution; the stratum corneum offered resistance to Delta(9)-THC diffusion, as evidenced by higher flux in stripped skin.

Conclusions:

• Brij 98 and higher BSA concentrations are effective receiver solutions for in vitro Delta(9)-THC skin permeation studies.
• The stratum corneum acts as a barrier to Delta(9)-THC diffusion across human skin.
• Established experimental conditions enhance the reliability of in vitro Delta(9)-THC dermal diffusion assessments.