Ex Vivo Dermal Permeability

Ex vivo dermal studies are used to assess the feasibility of transdermal administration, to rank-order compounds in terms of permeability or accumulation, and to optimize formulations.

Such studies are performed with human or porcine skin in Franz cells. Test formulations (gels, creams, ointments, patches, etc.) are applied to the upper (external) surface, and samples are removed at pre-determined time points from the reservoir containing buffer that is in contact with the lower (serosal) surface. Reference compounds are either co-dosed (if the test compound is in solution) or run in parallel (if the test compound is in some other type of formulation) for quality control. The skin is often extracted at the end of the study to quantify accumulation of the test compound.

It is possible to determine accumulation in different layers of the skin by tape stripping or heat separation. Transepidermal water loss (TEWL) may be measured as a proxy for skin dryness. Test formulations may also be incubated with tissue homogenates to assess the metabolic stability of the test article.

Study Purpose

Evaluate the dermal permeability and/or accumulation of test articles

Deliverables

• Flux or apparent permeability of the test article and reference compounds
• Percent recovery of the test article
• Comparison of the absorption potential of test article to that of reference compounds
• Comparison of test and reference formulations (if applicable)
• Accumulation in stratum corneum, epidermis, and dermis (if applicable)
• Demographics of human donor

Model Description

• Unidirectional permeability assessment of test article across frozen dermatomed human cadaver skin (male or female trunk region)
• Skin mounted in Franz cells thermostatically controlled at 37°C
• Test article may be dosed without formulation, or administered as a gel, cream, ointment, patch, or solution
• Suitability experiments may include assessment of chemical stability and/or non-specific binding
• Control compounds (atenolol and testosterone or caffeine) run in parallel
• Sampling from receiver compartment at five time points up to 30 hours
• Optional determination of test article accumulation in skin
• Optional stability assessment in skin homogenate

Benefits

• Screen formulations in human skin before clinical PK or bioequivalence studies
• Rank order compounds in terms of permeability
• Evaluate locally-acting dermal formulations and quantify dermal accumulation
• Absorption Systems provides in-house analytical and formulation services, along with consultative assistance in study design