Effect of Application Amounts on In Vitro Dermal Absorption Test Using Caffeine and Testosterone

Area of Science:

• Pharmacology and Toxicology
• Dermal Science
• Chemical Risk Assessment

Background:

• Dermal absorption is critical for chemical risk assessment.
• Understanding the impact of application dose on dermal absorption is essential for accurate risk evaluation.
• Caffeine and testosterone were selected as model compounds to investigate dermal absorption dynamics.

Purpose of the Study:

• To investigate the effect of varying application amounts on the dermal absorption of caffeine and testosterone.
• To determine an appropriate application dose for optimizing dermal absorption.
• To compare dermal absorption across different formulations (cream, solution) and skin types (rat, minipig).

Main Methods:

• In vitro dermal absorption studies utilizing Franz diffusion cells.
• Application of semisolid and liquid formulations containing caffeine and testosterone at doses of 5, 10, 25, and 50 mg/cm².
• Quantification of compound concentrations on skin surfaces, within skin layers (stratum corneum, epidermis, dermis), and in receptor fluid using LC-MS/MS or HPLC after 24 hours.

Main Results:

• Dermal absorption of both caffeine and testosterone decreased as the application amount increased, across both rat and minipig skin.
• Significantly lower dermal absorption percentages were observed at the highest application dose (50 mg/cm²) compared to lower doses (5 or 10 mg/cm²).
• This dose-dependent reduction in absorption was consistent for both cream and solution formulations.

Conclusions:

• Application dose significantly influences dermal absorption rates.
• Lower application doses (5-10 mg/cm²) result in more conservative and potentially higher dermal absorption.
• Findings suggest that optimizing application dose is crucial for accurate risk assessment and effective topical delivery of chemicals.