Improved method for determining partition and diffusion coefficients in human dermis.

Area of Science:

• Dermal drug delivery and absorption
• Pharmacokinetics and biotransport
• In vitro skin permeation studies

Background:

• Accurate partition and diffusion coefficients in lower skin layers are vital for estimating skin concentrations after topical application.
• These parameters significantly influence systemic absorption rates for highly lipophilic compounds.

Purpose of the Study:

• To describe methodology for more accurate in vitro measurements of partition and diffusion coefficients in human dermis.
• To investigate the influence of protein binding on dermal transport parameters.

Main Methods:

• Isolated human dermis was used in side-by-side diffusion cells.
• A dialysis membrane (5000 MW cut-off) was employed between the dermis and donor solution.
• Permeation and steady-state skin concentrations of DEET and diclofenac were measured using radiochemical techniques.

Main Results:

• For highly protein-bound diclofenac, dermis permeability and partition coefficient were significantly higher with the dialysis membrane.
• No significant differences were observed for moderately protein-bound DEET.
• Protein diffusion impacts transport and partitioning of highly protein-bound solutes in dermis.

Conclusions:

• In the absence of the stratum corneum, soluble protein diffusion must be considered for accurate transport and partitioning parameter estimation.
• This methodology improves the understanding of dermal absorption for various compounds.