Assessment of dermal bioavailability: predicting the input function for topical glucocorticoids using stratum corneum...

Area of Science:

• Dermatology
• Pharmacokinetics
• Drug Delivery

Background:

• Predicting topical drug bioavailability in skin is complex.
• Minimally invasive stratum corneum (SC) sampling offers a potential solution.
• Understanding drug penetration is crucial for effective topical therapies.

Purpose of the Study:

• To quantify the dermal delivery of betamethasone valerate (BMV) into the viable skin using SC sampling.
• To compare the efficacy of SC sampling with skin blanching response for assessing drug delivery.
• To determine drug uptake, clearance, and flux into the epidermis.

Main Methods:

• Applied three doses of Betnovate® cream (0.1% BMV) to healthy volunteers.
• Utilized tape-stripping to quantify BMV mass in the SC after uptake and clearance periods.
• Assessed skin blanching responses using a chromameter concurrently.

Main Results:

• BMV uptake into the SC varied significantly with dose, peaking at 5 mg cm⁻².
• Approximately 30% of SC drug was cleared within 6 hours.
• Estimated average drug flux into viable epidermis was 4 ng cm⁻² h⁻¹ with a clearance rate of 0.07 h⁻¹.
• Skin blanching was highly variable and dose-insensitive.

Conclusions:

• SC sampling provides quantitative metrics for corticosteroid delivery to the viable epidermis.
• This method is more sensitive and reliable than skin blanching for evaluating topical drug delivery.
• SC sampling can detect dose-dependent differences in drug delivery, aiding formulation development.