Ibuprofen epidermal levels after topical application in vitro: effect of formulation, application time, dose...

The influence of vehicle (two oil-in-water emulsions and two gels, each containing 10% or 5% ibuprofen) application time (0.5, 1, 2 h), applied dose (1.5, 3, 6, 12 mg/cm2), time (24 h after an 0.5 h application time), and occlusion on the epidermal concentration of ibuprofen was investigated. The drug concentration in the epidermis was measured by HPLC. All results were expressed as microgram drug/mg epidermal protein. The application time had no influence on the epidermal drug concentration, whereas the two gel formulations produced concentrations approximately twice those obtained with the emulsions. A significant positive correlation was found between the applied dose and the epidermal concentration for each formulation. After 24 h the amount of drug remaining in the epidermis was low (reduced by factors of 10-20). Occlusion produced higher concentrations, but only with the 2-h application time. The methods are reliable, and useful in ranking vehicles according to their ability to release ibuprofen into the epidermis. Future investigations should explore the relationship between epidermal concentration and anti-inflammatory efficacy in vivo.